مواضيع المحاضرة:
background image

Figure 3–6 shows the manner in which multiple numbers of nucleotides are

Organization of the Nucleotides to Form Two Strands of DNA Loosely Bound to Each Other.

DNA.

acid, and Figure 3–5 shows simple symbols for the four nucleotides that form

Figure 3–4 shows the chemical structure of deoxyadenylic

deoxycytidylic acids.

deoxyadenylic, deoxythymidylic, deoxyguanylic,

to form an acidic nucleotide. Four separate nucleotides are thus formed, one for

cule of phosphoric acid, one molecule of deoxyribose, and one of the four bases

The first stage in the formation of DNA is to combine one mole-

them, as illustrated in Figure 3–6.

molecule, and the nitrogenous bases lie between the two strands and connect

and deoxyribose form the two helical strands that are the backbone of the DNA

). The phosphoric acid

and two pyrimidines,

guanine,

(two purines,

deoxyribose,

involved in the formation of DNA. These include (1) 

Figure 3–3 shows the basic chemical compounds

few paragraphs.

bound together in a regular pattern, details of which are explained in the next

Figure 3–2. This molecule is composed of several simple chemical compounds

measured in the billions. A very short segment of such a molecule is shown in

long double-stranded helical molecules of DNA having molecular weights

In the cell nucleus, large numbers of genes are attached end on end in extremely

gen, and adenosine triphosphate (ATP).

cell, and they promote synthesis of all the cell chemicals, such as lipids, glyco-

instance, enzymes promote all the oxidative reactions that supply energy to the

that catalyze the different chemical reactions in the cells. For

lar organelles discussed in Chapter 2. However, by far the majority of the pro-

various lipids and carbohydrates, form the structures of the various intracellu-

which, in association with

structural proteins,

cally possible to form a very large number of different cellular proteins.

Because there are more than 30,000 different genes in each cell, it is theoreti-

this RNA then

ribonucleic acid (RNA);

deoxyribonucleic acid (DNA),

Figure 3–1 shows the general schema of genetic control. Each gene, which is

tures, which enzymes, which chemicals.

day function of all the body’s cells. The genes

from parents to children, but most people do not

the nuclei of all cells of the body, control heredity

Virtually everyone knows that the genes, located in

Synthesis, Cell Function,

C

H

A

P

T

E

R

 

3

27

Genetic Control of Protein

and Cell Reproduction

realize that these same genes also control day-to-

control cell function by determining which sub-
stances are synthesized within the cell—which struc-

a nucleic acid called 

automatically controls the

formation of another nucleic acid,
spreads throughout the cell to control the formation of a specific protein.

Some of the cellular proteins are 

teins are enzymes

Genes in the Cell Nucleus

Basic Building Blocks of DNA.

phosphoric acid, (2) a

sugar called 

and (3) four nitrogenous bases

adenine

and 

thymine and cytosine

Nucleotides.

each of the four bases:

and


background image

Introduction to Physiology: The Cell and General Physiology

28

Unit I

Cell structure

Cell enzymes

Gene (DNA)

RNA formation

Protein formation

Cell function

General schema by which the genes control cell function.

Figure 3–1

helix are purine and pyrimidine bases; these determine the “code”

bose. The internal molecules connecting the two strands of the

strands are composed of phosphoric acid and the sugar deoxyri-

The helical, double-stranded structure of the gene. The outside

Figure 3–2

of the gene.

C

C

H

Guanine

Cytosine

Purines

Pyrimidines

Phosphoric acid

Deoxyribose

Bases

Thymine

C

C

O

C

C

C

H

H

H

H

N

N

N

N

N

H

Adenine

C

C

N

C

C

C

H

C

C

C

C

H

H

O

H

H

H

O

O

H

O

H

P

O

O

H

O

H

H

N

H

H

N

N

N

O

C

H

C

H

C

O

N

H

N

N

H

H

H

H

C

C

O

O

N

C

N

H

H

H

H

H

H

C

H

C

H

Figure 3–3

The basic building blocks of DNA.


background image

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

29

C

C

N

C

C

C

H

H

N

H

H

N

N

N

P

O

O

O

H

C

C

C

C

H

H

O

H

H

O

O

C

H

H

H

H

H

Adenine

Phosphate

Deoxyribose

Figure 3–4

Deoxyadenylic acid, one of the nucleotides that make up DNA.

D

A

P

D

G

P

D

T

P

D

C

P

Deoxyadenylic acid

Deoxyguanylic acid

Deoxythymidylic acid

Deoxycytidylic acid

and one of the four nucleotide bases: A, adenine; T, thymine; 

Symbols for the four nucleotides that combine to form DNA. 

Figure 3–5

Each nucleotide contains phosphoric acid (P), deoxyribose (D),

G, guanine; or C, cytosine.

D

P

P

D

P

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

P

D

D

P

C

G

C

G

G

C

T

A

C

G

T

A

G

C

A

T

A

T

form the genetic code.

strand in Figure 3–7. It is these projecting bases that

the side of each DNA strand, as shown by the top

two strands of a DNA molecule are split apart, this

That is, when the

genetic code.

the formation of proteins in the cell. It does this by

The importance of DNA lies in its ability to control

molecule, as shown in Figure 3–2.

are present in each full turn of the helix in the DNA

and twist them into a helix. Ten pairs of nucleotides

ical perspective, one could merely pick up the two ends

To put the DNA of Figure 3–6 into its proper phys-

the two strands can pull apart with ease, and they do

AT. Because of the looseness of the hydrogen bonds,

pairs of bases is CG, CG, GC, TA, CG, TA, GC, AT, and

Thus, in Figure 3–6, the sequence of complementary

cytosine.

2. Each purine base 

strand, and

1. Each purine base 

are held together. But note the following:

and pyrimidine bases, the two respective DNA strands

deoxyribose molecules. Then, by means of loose

acid and deoxyribose molecules. In turn, purine and

DNA strand is comprised of alternating phosphoric

central dashed lines. Note that the backbone of each

weak cross-linkages, illustrated in Figure 3–6 by the

strands are, in turn, loosely bonded with each other by

bound together to form two strands of DNA. The two

Figure 3–6

Arrangement of deoxyribose nucleotides
in a double strand of DNA.

pyrimidine bases are attached to the sides of the

hydrogen bonds (dashed lines) between the purine

adenine of one strand always

bonds with a pyrimidine base thymine of the other

guanine always bonds with a

pyrimidine base 

so many times during the course of their function in
the cell.

Genetic Code

means of the so-called 

exposes the purine and pyrimidine bases projecting to


background image

cytosine,

adenine, guanine,

These nucleotides contain the bases 

rate nucleotides are used in the formation of RNA.

described for DNA synthesis. Here again, four sepa-

RNA nucleotides,

of RNA form 

The basic building blocks

dine,

ture. Second, thymine is replaced by another pyrimi-

ribose,

in the formation of RNA. In its place is another sugar

two differences. First, the sugar deoxyribose is not used

RNA are almost the same as those of DNA, except for

The basic building blocks of

cytoplasm.

these codons, in turn, will control the sequence of

) in the RNA;

The code triplets in the DNA cause formation of 

used as a template for synthesis of an RNA molecule.

molecule separate temporarily; one of these strands is

During synthesis of RNA, the two strands of the DNA

where it controls protein synthesis.

nuclear pores into the cytoplasmic compartment,

The RNA, in turn, diffuses from the nucleus through

ferred to the RNA; this process is called 

nucleus. Thus, as shown in Figure 3–7, the code is trans-

mation of which is controlled by the DNA of the

mediary of another type of nucleic acid, RNA, the for-

of the cytoplasm. This is achieved through the inter-

the cytoplasm, there must be some means for the DNA

Because the DNA is located in the nucleus of the cell,

of Transcription

Cytoplasm—The Process 

an RNA Code in the Cell

Nucleus Is Transferred to 

proline, serine,

acids,

follow this genetic code through Figures 3–7 and 3–8,

separated from one another by the arrows. As we

the genetic code GGC, AGA, CTT, the triplets being

the top strand of DNA, reading from left to right, has

to be synthesized in the cell. Note in Figure 3–6 that

The successive triplets eventually control the

word.

bases—that is, each three successive bases is a 

The genetic code consists of successive “triplets” of

Introduction to Physiology: The Cell and General Physiology

30

Unit I

code

sequence of amino acids in a protein molecule that is

we see that these three respective triplets are respon-
sible for successive placement of the three amino

and  glutamic acid, in a newly

formed molecule of protein.

The DNA Code in the Cell

yet most of the functions of the cell are carried out in

genes of the nucleus to control the chemical reactions

transcription.

Synthesis of RNA

com-

plementary code triplets (called codons

amino acids in a protein to be synthesized in the cell

Basic Building Blocks of RNA.

of slightly different composition,

containing an

extra hydroxyl ion appended to the ribose ring struc-

uracil.

Formation of RNA Nucleotides.

exactly as previously

and uracil. Note that these are the same bases

P

P

R

P

P

R

D

G

P

D

G

P

D

C

P

D

A

P

D

G

P

D

A

P

D

P

D

P

D

T

P

C

T

DNA strand

RNA molecule

RNA polymerase

Triphosphate

R

C

C

P

R

G

R

U

C

P

R

U

P

P

R

G

P

P

P

R

A

P

genetic code from the gene to the 

with a strand of DNA to form a 

Figure 3–7

Combination of ribose nucleotides

molecule of RNA that carries the

cytoplasm. The RNA polymerase
enzyme moves along the DNA
strand and builds the RNA molecule.

P

P

R

Proline

Serine

Glutamic acid

R

C

C

P

R

G

P

R

U

P

R

C

P

R

U

P

R

G

P

R

A

P

R

A

growing RNA chain.

respectively, to the

proline,

attachment of the three amino acids 

“codons”—CCG, UCU, and GAA—which control

Portion of an RNA molecule, showing three RNA

Figure 3–8

serine, and  glutamic acid,


background image

RNA chain. The ribose nucleotide bases always

form to the

Thus, the code that is present in the DNA strand is

from the DNA and is released into the

strand. Thus, the RNA chain is forced away

rebonding with its own complementary DNA

away, because the DNA has a high affinity for

hydrogen bonds with the DNA template break

d. As the new RNA strand is formed, its weak

form still more new RNA chains.

to break away from the DNA strand. Then the

polymerase and the newly formed RNA chain

chain-terminating sequence;

sequence of DNA nucleotides called the 

end of the DNA gene, it encounters a new

c. When the RNA polymerase reaches the 

the ribose on the end of the growing RNA

broken high-energy phosphate bonds; this

away from each of these RNA nucleotides,

b. Then, one at a time, the RNA polymerase

the base of an RNA nucleotide in the

between the end base of the DNA strand and

a. First, it causes a hydrogen bond to form

forming RNA chain by the following steps:

activated RNA nucleotide to the end of the newly

As it moves along, it adds at each stage a new

two DNA strands at each stage of its movement.

strand, temporarily unwinding and separating the

3. Then the polymerase moves along the DNA

of the unwound portions of the two strands.

about two turns of the DNA helix and separation

promoter, the polymerase causes unwinding of

2. After the RNA polymerase attaches to the

of the RNA molecule.

it. This is the essential step for initiating formation

The RNA polymerase has an

promoter.

1. In the DNA strand immediately ahead of the

for formation of the RNA molecule. They are as

This is a large protein

RNA polymerase.

of an enzyme,

the manner shown in Figure 3–7 under the influence

Assembly of the RNA molecule is accomplished in 

of “Transcription”

Strand as a Template—The Process 

Assembly of the RNA Chain from

RNA nucleotide at the end of the developing RNA

each of the nucleotides, and this energy is used to

large quantities of ATP energy are made available to

The result of this activation process is that 

derived from ATP in the cell.

RNA chain formation). These last two phosphates are

3–7 by the two RNA nucleotides to the far right during

phate radicals to form triphosphates (shown in Figure

This

RNA polymerase.

nucleotides by an enzyme,

the synthesis of RNA is “activation” of the RNA

The next step in 

thymine in DNA.

as in DNA, except that uracil in RNA replaces

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

31

“Activation” of the RNA Nucleotides.

occurs by adding to each nucleotide two extra phos-

combined with the nucleotide by high-energy phos-
phate bonds

promote the chemical reactions that add each new

chain.

Activated Nucleotides Using the DNA

enzyme that has many functional properties necessary

follows:

initial gene is a sequence of nucleotides called 
the 
appropriate complementary structure that
recognizes this promoter and becomes attached to

nucleoplasm.

breaks two of the three phosphate radicals

liberating large amounts of energy from the

energy is used to cause covalent linkage of the
remaining phosphate on the nucleotide with

chain.

this causes the

polymerase can be used again and again to

nucleoplasm.

eventually transmitted in complementary

combine with the deoxyribose bases in the following
combinations:

the RNA codons for the 20 common amino acids

Table 3–1 gives

Figure 3–7.

DNA molecule to the RNA molecule is shown in

tamic acid. The transcription of these codons from the

the codons for the amino acids proline, serine, and glu-

RNA. Its codons are CCG, UCU, and GAA. These are

to the code triplets of the DNA genes. Figure 3–8

thousand RNA nucleotides in unpaired strands, and

strands that are suspended in the cytoplasm. These

molecules are long, single RNA

Messenger RNA

ribosomes,

different proteins, forms 

which, along with about 75

Ribosomal RNA,

the protein molecule.

Transfer RNA,

the cytoplasm for controlling the type of protein

Messenger RNA,

types of RNA, each of which plays an independent and

There are three different

Three Different Types of RNA.

thymine    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

adenine

adenine     . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

uracil

cytosine    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

guanine

guanine

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

cytosine

DNA Base

RNA Base

entirely different role in protein formation:
1.

which carries the genetic code to

formed.

2.

which transports activated amino

acids to the ribosomes to be used in assembling

3.

the physical

and chemical structures on which protein
molecules are actually assembled.

Messenger RNA—The Codons

molecules are composed of several hundred to several

they contain codons that are exactly complementary

shows a small segment of a molecule of messenger

RNA Codons for the Different Amino Acids.


background image

formation of the protein molecule, the anticodon bases

cloverleaf configuration shown in Figure 3–9). During

of the transfer RNA molecule (at the bottom of the

This is located approximately in the middle 

RNA that allows it to recognize a specific codon is

messenger RNA. The specific code in the transfer

RNA also have specificity for a particular codon in the

protein chain, it is essential that each type of transfer

Because the function of transfer RNA is to cause

is always an adenylic acid; it is to this that the trans-

that shown in Figure 3–9. At one end of the molecule

parison with messenger RNA. It is a folded chain of

nucleotides, is a relatively small molecule in com-

Transfer RNA, which contains only about 80

protein molecule.

codon on the messenger RNA (described later) and

specific type of transfer RNA recognizes a particular

protein molecules are forming. In the ribosomes, each

specific type of amino acid to the ribosomes, where

transfer RNA then acts as a 

acids that are to be incorporated into proteins. The

RNA combines specifically with 1 of the 20 amino

the protein is being synthesized. Each type of transfer

transfer RNA,

Another type of RNA that plays an essential role in

Transfer RNA—The Anticodons

for “chain-initiating” and CT for “chain-terminating.”

Table 3–1, these two types of codons are designated CI

sent “stop manufacturing the protein molecule.” In

turing the protein molecule,” and three codons repre-

also, one codon represents the signal “start manufac-

found in protein molecules. Note that most of the

Introduction to Physiology: The Cell and General Physiology

32

Unit I

amino acids are represented by more than one codon;

protein synthesis is called 

because it

transfers amino acid molecules to protein molecules as

carrier to transport its 

thereby delivers the appropriate amino acid to the
appropriate place in the chain of the newly forming

nucleotides with a cloverleaf appearance similar to

ported amino acid attaches at a hydroxyl group of the
ribose in the adenylic acid.

attachment of a specific amino acid to a forming

again a triplet of nucleotide bases and is called an anti-
codon.

combine loosely by hydrogen bonding with the codon

AUG GCC UGU CAU GCC UUU UCC CCC AAA CAG GAC UAU

RNA movement

Ribosome

Ribosome

Transfer RNA

Forming protein

Alanine

Cysteine

Histidine

Alanine

Phenylalanine

Serine

Proline

Messenger

Start codon

GGG

protein.

each specific amino acid to the newly forming

some. The transfer RNA molecule transports

an amino acid is added to the growing protein

ribosomes. As each “codon” passes through, 

A messenger RNA strand is moving through two

Figure 3–9

chain, which is shown in the right-hand ribo-

Table 3–1

Stop (CT)

UAA

UAG

UGA

Start (CI)

AUG

Valine

GUU

GUC

GUA

GUG

Tyrosine

UAU

UAC

Tryptophan

UGG

Threonine

ACU

ACC

ACA

ACG

Serine

UCU

UCC

UCA

UCG

AGC

AGU

Proline

CCU

CCC

CCA

CCG

Phenylalanine

UUU

UUC

Methionine

AUG

Lysine

AAA

AAG

Leucine

CUU

CUC

CUA

CUG

UUA

UUG

Isoleucine

AUU

AUC

AUA

Histidine

CAU

CAC

Glycine

GGU

GGC

GGA

GGG

Glutamine

CAA

CAG

Glutamic acid

GAA

GAG

Cysteine

UGU

UGC

Aspartic acid

GAU

GAC

Asparagine

AAU

AAC

Arginine

CGU

CGC

CGA

CGG

AGA

AGG

Alanine

GCU

GCC

GCA

GCG

Amino Acid

RNA

Codons

RNA Codons for Amino Acids and for Start and Stop

CI, chain-initiating; CT, chain-terminating.


background image

ing: (1) Each amino acid is 

. The stages of the reactions are the follow-

, AA

reactions for three separate amino acids, AA

shown in Figure 3–11. This figure shows representative

instead of into the endoplasmic reticulum. These pro-

the ribosomes are released directly into the cytosol

tory vesicles are formed, most proteins synthesized by

Yet it should be noted that except in glandular cells

response to the same strand of messenger RNA. Note

endoplasmic reticulum. Note the process of translation

senger RNA to the ribosomes and the manner in

Figure 3–10 shows the functional relation of mes-

matrix. This gives a granular appearance to those por-

reticulum; this causes these molecules to penetrate the

attached to the endoplasmic reticulum. This occurs

Chapter 2, it was noted that many ribosomes become

chemical reactions take place.

somes for given types of protein. The ribosome is

in any ribosome; that is, there is no specificity of ribo-

RNA can cause the formation of a protein molecule

polyribosomes.

These clusters are called 

attached to a single messenger RNA at the same time.

ribosomes frequently occur, 3 to 10 ribosomes being

development in each ribosome. As a result, clusters of

3–10. The protein molecules are in different stages of

as shown at the bottom left in Figure 3–9 and in Figure

same time because the initial end of the RNA strand

A single messenger RNA molecule can

protein molecule is freed into the cytoplasm.

“chain-terminating”) codon slips past the ribosome,

back head of a tape recorder. Then, when a “stop” (or

way that a tape is “read” as it passes through the play-

the codons of the messenger RNA in much the same

Thus, the ribosome reads

through the ribosome, a protein molecule is formed—

shown in Figure 3–9, while the messenger RNA travels

bases called the “chain-initiating” codon. Then, as

cule specified by an appropriate sequence of RNA

beginning at a predetermined end of the RNA mole-

with a ribosome, it travels through the ribosome,

When a molecule of messenger RNA comes in contact

of “Translation”

Formation of Proteins on 

does not contain mature ribosomes.

cell, but not in the cell nucleus, because the nucleus

Therefore, proteins are formed in the cytoplasm of the

are assembled to form mature, functional ribosomes.

plasm. After the subunits enter the cytoplasm, they 

the nuclear envelope to almost all parts of the cyto-

somes. These subunits are then released from the

with “ribosomal proteins” to form granular condensa-

is specially processed in the nucleolus, where it binds

the nucleolus may not even be seen. Ribosomal RNA

structure, whereas in cells that synthesize little protein,

ture large amounts of protein, the nucleolus is a large

are being synthesized, as occurs in cells that manufac-

chromosomes. When large amounts of ribosomal RNA

nucleolus,

As the ribosomal RNA forms, it collects in the

mal RNA required for cellular function.

pairs of chromosomes in the nucleus, and each of these

for formation of ribosomal RNA are located in five

The DNA genes

Thus, the ribosome acts as a manufacturing plant in

messenger RNA

tion into the developing protein molecule, whereas

transfer RNA

with the other two types of RNA as well:

thesized. However, it always functions in association

The ribosome is the physical structure in the cyto-

molecules.

remainder of the ribosome is protein, containing about

The

ribosome.

The third type of RNA in the cell is ribosomal RNA;

forming protein molecule.

the messenger RNA chain, thus establishing the

bases of the messenger RNA. In this way, the respec-

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

33

tive amino acids are lined up one after another along

appropriate sequence of amino acids in the newly

Ribosomal RNA

it constitutes about 60 per cent of the 

75 types of proteins that are both structural proteins
and enzymes needed in the manufacture of protein

plasm on which protein molecules are actually syn-

transports amino acids to the ribosome for incorpora-

provides the information necessary

for sequencing the amino acids in proper order for
each specific type of protein to be manufactured.

which the protein molecules are formed.

Formation of Ribosomes in the Nucleolus.

chromosomes contains many duplicates of these par-
ticular genes because of the large amounts of riboso-

a specialized structure lying adjacent to the

tion products that are primordial subunits of ribo-

nucleolus and transported through the large pores of

the Ribosomes—The Process 

a process called translation.

the end of a protein molecule is signaled and the

Polyribosomes.

form protein molecules in several ribosomes at the

can pass to a successive ribosome as it leaves the first,

It is especially important to note that a messenger

simply the physical manufacturing plant in which the

Many Ribosomes Attach to the Endoplasmic Reticulum.

In

because the initial ends of many forming protein mol-
ecules have amino acid sequences that immediately
attach to specific receptor sites on the endoplasmic

reticulum wall and enter the endoplasmic reticulum

tions of the reticulum where proteins are being formed
and entering the matrix of the reticulum.

which the ribosomes attach to the membrane of the

occurring in several ribosomes at the same time in

also the newly forming polypeptide (protein) chains
passing through the endoplasmic reticulum membrane
into the endoplasmic matrix.

in which large amounts of protein-containing secre-

teins are enzymes and internal structural proteins of
the cell.

Chemical Steps in Protein Synthesis.

Some of the chemical

events that occur in synthesis of a protein molecule are

1

2

,

and AA

20

activated by a chemical


background image

The successive amino acids in the

for each amino acid added to the protein chain. Thus,

bonds, making a total of four high-energy bonds used

to the protein chain. These chemical events require

the successive amino acids, thus adding progressively

to form a protein molecule. Then, under the influence

porarily to its specific codon of the messenger RNA,

the anticodon of the transfer RNA attaches tem-

messenger RNA molecule in the ribosome, where 

monophosphate. (3) The transfer RNA carrying the

and, at the same time, releases the adenosine

specific transfer RNA to form an amino acid–tRNA

having an excess of energy, then 

bonds in the process. (2) The activated amino acid,

process in which ATP combines with the amino acid

Introduction to Physiology: The Cell and General Physiology

34

Unit I

to form an adenosine monophosphate complex with the
amino acid, 
giving up two high-energy phosphate

combines with its 

complex

amino acid complex then comes in contact with the

thus lining up the amino acid in appropriate sequence

of the enzyme peptidyl transferase (one of the proteins
in the ribosome), peptide bonds are formed between

energy from two additional high-energy phosphate

the synthesis of proteins is one of the most energy-con-
suming processes of the cell.

Peptide Linkage.

protein chain combine with one another according to
the typical reaction:

Transfer RNA

Messenger

RNA

Ribosome

Amino acid

Polypeptide
chain

Large

subunit

Small

subunit

(Courtesy of Dr. Don W. Fawcett,

the formation of protein molecules.

the endoplasmic reticulum during

as well as their functional relation to

Physical structure of the ribosomes,

Figure 3–10

messenger RNA, transfer RNA, and

Montana.)

Protein chain

+

ATP

tRNA

1

tRNA

1

+

GCC

Messenger RNA

GCC

GTP

+

ATP

AMP

+

tRNA

2

tRNA

2

+

+

ATP

AMP

+

tRNA

20

tRNA

20

+

tRNA

5

UGU

UGU

GTP

tRNA

3

AAU

AAU

GTP

tRNA

9

CAU

CAU

GTP

tRNA

2

CGU

CGU

GTP

tRNA

13

AUG

AUG

GTP

tRNA

20

GUU

GUU

GTP

Activated amino acid

Amino acid

RNA-amino acyl complex

Complex between tRNA,
messenger RNA, and
amino acid

AMP

+

tRNA

1

¸

Ô

Ô

˝

Ô

Ô

˛

AA

1

AA

1

AA

1

AA

1

AA

1

AA

2

AA

2

AA

2

AA

20

AA

20

AA

20

AA

5

AA

5

AA

3

AA

3

AA

9

AA

9

AA

2

AA

2

AA

13

AA

13

AA

20

AA

20

a protein molecule.

Chemical events in the formation of

Figure 3–11

O

OH

C

C

R

NH

2

R

COOH

C

N

H

H

O

C

C

R

NH

2

H

2

O

R

COOH

C

N

H

+

+


background image

(more than 30,000 genes in all), there is at least one

tions of the cell in step with one another. For each gene

respective genes must be controlled as well; otherwise,

of the cells. However, the degree of activation of

From our discussion thus far, it is clear that the genes

Biochemical Activity in Cells

Control of Gene Function and

Chapters 67 through 69. It is by means of all these 

to carbohydrate, lipid, and protein metabolism in

pyrimidines, and hundreds of other substances. We

enzymes promote synthesis of lipids, glycogen, purines,

chemical reactions that take place in cells. These

As each additional amino acid is added, an

linkage.

in a single molecule. This process is called 

cessive amino acids bond with each other, resulting 

water, and the two reactive sites left on the two suc-

other amino acid is removed. These combine to form

acid, and a hydrogen (H

In this chemical reaction, a hydroxyl radical (OH

moter, thereby blocking transcription of the genes of

prevent attachment of RNA polymerase to the pro-

because a “regulatory” protein can bind here and

promoter. This area is called a 

Also note in Figure 3–12 an addi-

“Repressor Operator.”

strand to synthesize RNA. Therefore, the promoter is

moter before it can begin traveling along the DNA

discussed. The polymerase must bind with this pro-

has specific affinity for RNA polymerase, as already

This is a group of nucleotides that

promoter.

Note in the figure the segment on the DNA strand

structural genes are shown in an operon, and it is

In Figure 3–12, three respective 

structural genes.

and the genes respon-

DNA strand is called an 

the same chromosomal DNA strand. This area of the

special protein enzyme. Formation of all the enzymes

tions, and each of these reactions is catalyzed by a

thesis—Function of the Promoter.

Genetic Regulation

vation of the genes themselves is controlled, and the

chemical activities in the cell are controlled. One of

There are basically two methods by which the bio-

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

35

these is genetic regulation, in which the degree of acti-

other is enzyme regulation, in which the activity levels
of already formed enzymes in the cell are controlled.

The “Operon” of the Cell and Its Control of Biochemical Syn-

Synthesis of a cellular

biochemical product usually requires a series of reac-

needed for the synthetic process often is controlled by
a sequence of genes located one after the other on 

operon,

sible for forming the respective enzymes are called

demonstrated that they control the formation of three
respective enzymes that in turn cause synthesis of a
specific intracellular product.

called the 

an essential element for activating the operon.

Control of the Operon by a “Repressor Protein”—The 

tional band of nucleotides lying in the middle of the

repressor operator

)

is removed from the COOH portion of the first amino

+

) of the NH

2

portion of the

peptide

additional peptide linkage is formed.

Synthesis of Other
Substances in the Cell

Many thousand protein enzymes formed in the
manner just described control essentially all the other

discuss many of these synthetic processes in relation

substances that the many functions of the cells are 
performed.

control both the physical and the chemical functions

some parts of the cell might overgrow or some chem-
ical reactions might overact until they kill the cell.
Each cell has powerful internal feedback control
mechanisms that keep the various functional opera-

such feedback mechanism.

Enzyme B

Enzyme C

¸

Ô

Ô

Ô

˝

Ô

Ô

Ô

˛

Structural

Gene A

Promoter

Inhibition of

the operator

Enzyme A

Synthesized

product

Substrates

(Negative feedback)

Repressor

operator

Activator

operator

Operon

Structural

Gene B

Structural

Gene C

controlling the concentration of the product itself.

the function of the operon, in this way automatically

sized product exerts negative feedback to inhibit

protein intracellular product, such as an intra-

to control synthesis of a non

operon

Figure 3–12

Function of an 

cellular metabolic chemical. Note that the synthe-


background image

Thus, cAMP acts as an enzyme activator for the

their energy used for replenishment of the ATP stores.

glycogen-splitting enzyme phosphorylase, liberating

ence of this cAMP, in turn, immediately activates the

formed as a breakdown product of the ATP; the pres-

in a cell. In this case, a considerable amount of cyclic

this occurs when most of the ATP has been depleted

often can be activated when needed. An example of

purines, pyrimidines, vitamins, and other substances.

intracellular concentrations of multiple amino acids,

feedback control; it is responsible for controlling 

inactivating the first enzyme: this prevents buildup of

tivates it. One can readily recognize the importance of

enzymes, usually binding directly with the enzyme and

enzyme in a sequence, rather than on the subsequent

specific enzyme systems that synthesize them. Almost

cific intracellular enzymes. Thus, enzyme regulation

regulation, some cell activities are controlled by intra-

Control of Intracellular Function 

and products of carbohydrate, lipid, and protein

amino acid derivatives, and intermediate substrates

trolling intracellular concentrations of amino acids,

genetic activity can be controlled is not surprising. The

in each human cell, the large number of ways in which

factors, thus controlling the chemical machinery

some of the body’s hormones, can activate specific

addition, signals from outside the cell, such as

are used for establishing proper cell function. In

chromosome. Thus, still higher orders of control

“transcriptor factor” controls the actual rate of

transcription can occur. Even then, some specific

one part at a time so that partial RNA

RNA. However, multiple control mechanisms are

this compacted state, it cannot function to form

by still other proteins. As long as the DNA is in

histones,

Within each chromosome, the DNA is wound

chromosomes.

in specific structural units, the 

4. In nucleated cells, the nuclear DNA is packaged

translation by the ribosomes.

formation in the cytoplasm during RNA

rarely, control might occur at the level of protein

before they are released into the cytoplasm;

processing of the RNA molecules in the nucleus

not even at the DNA strand itself but during the

farther along the strand. Sometimes the control is

point of transcription on the DNA strand but

3. Some operons are controlled not at the starting

simultaneously in this manner, all the operons

operon. When multiple operons are controlled

regulatory protein. In some instances, the same

2. Occasionally, many different operons are

complex of the nucleus. That is, the regulatory

1. An operon frequently is controlled by a

2 decades. Without giving details, let us list some of

Variations in the basic mechanism for control of the

Other Mechanisms for Control of Transcription by the Operon.

product is controlled automatically.

active. In this way, the desired concentration of the

tration decreases, the operon once again becomes

becomes dormant. Conversely, when the synthesized

dant enough for proper cell function, the operon

case, the operon becomes inhibited. Therefore, once

to break its bond with the activator operator. In either

for its synthesis. It can do this either by causing a 

Figure 3–12 that the presence of a critical amount 

Finally, note in

operon. Therefore, a regulatory protein of this type is

lymerase to the promoter, in this way activating the

binds to this operator, it helps attract the RNA po-

ahead of the promoter. When a regulatory protein

activator operator,

Note in Figure 3–12 another operator,

tor Operator.”

this operon. Such a negative regulatory protein is

Introduction to Physiology: The Cell and General Physiology

36

Unit I

called a repressor protein.

Control of the Operon by an “Activator Protein”—The “Activa-

called the 

that lies adjacent to but

called an activator protein.

Negative Feedback Control of the Operon.

of a synthesized product in the cell can cause negative
feedback inhibition of the operon that is responsible

regulatory repressor protein to bind at the repressor
operator or by causing a regulatory activator protein

the required synthesized product has become abun-

product becomes degraded in the cell and its concen-

operon have been discovered with rapidity in the past

them:

regulatory gene located elsewhere in the genetic

gene causes the formation of a regulatory protein
that in turn acts either as an activator or as a
repressor substance to control the operon.

controlled at the same time by the same

regulatory protein functions as an activator 
for one operon and as a repressor for another

that function together are called a regulon.

around small proteins called 

which in

turn are held tightly together in a compacted state

beginning to be discovered that can cause selected
areas of chromosomes to become decompacted

transcription by the separate operon in the

chromosomal areas and specific transcription

for function of the cell.

Because there are more than 30,000 different genes

gene control systems are especially important for con-

metabolism.

by Enzyme Regulation

In addition to control of cell function by genetic 

cellular inhibitors or activators that act directly on spe-

represents a second category of mechanisms by which
cellular biochemical functions can be controlled.

Enzyme Inhibition.

Some chemical substances formed in

the cell have direct feedback effects in inhibiting the

always the synthesized product acts on the first

causing an allosteric conformational change that inac-

intermediary products that are not used.

Enzyme inhibition is another example of negative

Enzyme Activation.

Enzymes that are normally inactive

adenosine monophosphate (cAMP) begins to be

glucose molecules that are rapidly metabolized and


background image

These replicas become the DNA in the two new

of all DNA.

hours. The net result is two exact 

hours before mitosis, and this is completed in 4 to 8

The DNA begins to be duplicated some 5 to 10

place.

mosomes.

replication (duplication) of all DNA in the chro-

cell, reproduction begins in the nucleus itself. The first

with Replication of DNA

Cell Reproduction Begins 

human body for most nerve cells.

ent cells of the body actually have life cycle periods

the uninhibited life cycle of the cell. Therefore, differ-

duction, inhibitory factors almost always slow or stop

interphase.

represented by the interval between mitosis, called

of the life cycle of even rapidly reproducing cells is

only about 30 minutes, so that more than 95 per cent

later. The actual stage of mitosis, however, lasts for

of mitosis are shown in Figure 3–13 and are described

sion of the cell into two new daughter cells. The events

little as 10 to 30 hours. It is terminated by a series of

this life cycle may be as

When mammalian cells 

The life cycle of a cell is the period

life, it is the DNA-genetic system.

functioning body. Thus, if there is any central theme to

being, from the single-cell fertilized ovum to the whole

new cells. In this way, the all-important genetic system

processes. The genes and their regulatory mechanisms

tous role that the DNA-genetic system plays in all life

Controls Cell Reproduction

or more of the intracellular control systems.

needed. But on occasion, substances from without the

control systems that continually monitor the cell’s 

systems can be either activated or inhibited. These reg-

activated or inhibited, and likewise, the enzyme

nism of enzyme regulation. The genes can be either

quantities of different cellular constituents: (1) the

In summary, there are two principal methods

Summary.

times.

for these two substances, resulting in almost exactly 

activate the purine enzymes. In this way, there is con-

versely, the pyrimidines inhibit their own enzymes but

the enzymes for formation of pyrimidines. Con-

formation of additional purines. However, they 

formed, they 

for formation of DNA and RNA. When purines are

of the purines and pyrimidines. These substances are

intracellular ATP concentration.

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

37

enzyme phosphorylase and thereby helps control

Another interesting instance of both enzyme inhi-

bition and enzyme activation occurs in the formation

needed by the cell in approximately equal quantities

inhibit the enzymes that are required for

acti-

vate

tinual cross-feed between the synthesizing systems 

equal amounts of the two substances in the cells at all

by which cells control proper proportions and proper

mechanism of genetic regulation and (2) the mecha-

ulatory mechanisms most often function as feedback

biochemical composition and make corrections as

cell (especially some of the hormones discussed
throughout this text) also control the intracellular 
biochemical reactions by activating or inhibiting one

The DNA-Genetic System Also

Cell reproduction is another example of the ubiqui-

determine the growth characteristics of the cells and
also when or whether these cells will divide to form

controls each stage in the development of the human

Life Cycle of the Cell.

from cell reproduction to the next cell reproduction.

are not inhibited and are repro-

ducing as rapidly as they can,

distinct physical events called mitosis that cause divi-

Except in special conditions of rapid cellular repro-

that vary from as little as 10 hours for highly stimu-
lated bone marrow cells to an entire lifetime of the

As is true of almost all other important events in the

step is 

Only after this has occurred can mitosis take

replicas

A

B

C

D

E

F

G

H

Centromere

Nucleolus

Centriole

Aster

Chromosome

Nuclear
membrane

(From Margaret C. Gladbach, Estate of Mary E. and Dan Todd,

Telophase.

Prometaphase. 

Prophase. 

Stages of cell reproduction. 

Figure 3–13

A, B, and  C,

D,

E, Metaphase. F, Anaphase. and H,

Kansas.)


background image

first events of mitosis takes place in the cytoplasm,

cells, mitosis follows automatically within 1 or 2 hours.

been replicated to form the two chromatids, in many

mitosis.

The actual process by which the cell splits into two new

chromatids.

located near their center. These duplicated

helixes collect new protein molecules as needed. The

the DNA helixes has been completed; the new DNA

and enzymes.

genetic regulatory machinery, as activators, inhibitors,

mal structural proteins and, in connection with the

nents of chromosomes, functioning both as chromoso-

RNA.

the DNA and to allow small segments at a time to form

DNA. Further, some of the regulatory proteins have

either the formation of RNA or the replication of new

is packaged tightly, it cannot function as a template for

ulation of DNA activity because as long as the DNA

The histone cores play an important role in the reg-

core after another.

each DNA helix are coiled sequentially around one

numbers of small, bobbin-like cores. Small segments of

The histones are organized into vast

histones.

large amount of protein in the chromosome, composed

In addition to DNA in the chromosome, there is a

not the case.

genes also exist in pairs, although occasionally this is

to each other, so it is usually stated that the different

arranged in 23 pairs. Most of the genes in the two chro-

mosomes. The human cell contains 46 chromosomes

The DNA helixes of the nucleus are packaged in chro-

despite mutations.

almost identical genes. Therefore, one functional gene

a further protection, however, each human genome is

in the passage of the genome from parent to child. As

human generation to another is about 30 years, one

death. Yet, given that there are 30,000 or more genes

cell rather than a needed protein, often leading to

The muta-

mistake is made, this is called a 

tion process rarely makes a mistake. But when a

Because of repair and proofreading, the transcrip-

proofreading.

DNA 

cation. This repair process is referred to as 

polymerases and DNA ligases that are used in repli-

tary nucleotides. This is achieved by the same DNA

plate strand, special enzymes cut out the defective

wherever inappropriate DNA nucleotides have been

repair and “proofreading” of the DNA strands. That is,

beginning of mitosis, there is a period of very active

the hour or so between DNA replication and the

DNA Repair, DNA “Proofreading,” and “Mutation.”

separation, and then resplice the helix. Thus, the

length, rotate each segment enough to cause

special mechanism. This is achieved by enzymes

impossible for the two newly formed DNA helixes

have millions of helix turns, it would be

6. Because the DNA helixes in each chromosome

Therefore, two DNA helixes are coiled together.

original DNA strand that was used as its template.

5. Each newly formed strand of DNA remains

enzyme.

subunits are joined together by the DNA ligase

entire strand is replicated. Then the ends of the

4. Formation of each new DNA strand occurs

phosphate bonds to energize these attachments.

nucleotides to one another, using high-energy

causes bonding of successive DNA

DNA ligase,

DNA template strand while another enzyme,

polymerase. It attaches to and moves along the

which is comparable to RNA

polymerase,

DNA

3. The principal enzymes for replicating DNA 

RNA.

portions of them, as occurs in the transcription of

replicated from end to end, rather than small

2. Both entire strands of the DNA helix are

are replicated, not simply one of them.

1. Both strands of the DNA in each chromosome

scribed in response to DNA, except for a few impor-

replicated in much the same way that RNA is tran-

DNA is

place that will lead to the mitotic process.

this period, preliminary changes are beginning to take

2 hours before mitosis begins abruptly. Even during

replication of the DNA, there is another period of 1 to

daughter cells that will be formed at mitosis. After

Introduction to Physiology: The Cell and General Physiology

38

Unit I

Chemical and Physical Events of DNA Replication.

tant differences:

are a complex of multiple enzymes called 

simultaneously in hundreds of segments along
each of the two strands of the helix until the

attached by loose hydrogen bonding to the

are approximately 6 centimeters in length and

to uncoil from each other were it not for some

that periodically cut each helix along its entire

two new helixes become uncoiled.

During

matched up with the nucleotides of the original tem-

areas and replace these with appropriate complemen-

mutation.

tion causes formation of some abnormal protein in the

abnormal cellular function and sometimes even cell

in the human genome and that the period from one

would expect as many as 10 or many more mutations

represented by two separate sets of chromosomes with

of each pair is almost always available to the child

Chromosomes and Their Replication

mosomes of each pair are identical or almost identical

mainly of many small molecules of electropositively
charged 

been shown to decondense the histone packaging of

Several nonhistone proteins are also major compo-

Replication of the chromosomes in their entirety

occurs during the next few minutes after replication of

two newly formed chromosomes remain attached to
each other (until time for mitosis) at a point called the
centromere
but still attached chromosomes are called 

Cell Mitosis

cells is called 

Once each chromosome has

Mitotic Apparatus: Function of the Centrioles.

One of the

occurring during the latter part of interphase in or


background image

allowed to collect in the culture medium. This, too,

Third, cells grown in tissue culture often stop growing

they contact a solid object, and then growth stops.

cells are grown in tissue culture; the cells grow until

have run out of space for growth. This occurs when

Second, most normal cells stop growing when they

as the pancreas, fail to grow without a growth factor

For instance, the epithelial cells of some glands, such

in the blood, but others originate in adjacent tissues.

from other parts of the body. Some of these circulate

growth factors

three ways in which growth can be controlled. First,

the body. However, experiments have shown at least

We know little about the mechanisms that maintain

ated cells such as nerve and muscle cells.

marrow, subcutaneous tissue, intestinal epithelium,

liver mass returns almost to normal. The same occurs

the liver can be removed surgically, and the cells of 

instance, in some young animals, seven eighths of 

appropriate numbers of them are again available. For

In certain tissues, an insufficiency of some types of

fetal life.

life of a person, except during the original period of

ated muscle cells, do not reproduce during the entire

years. A few cells, such as the neurons and most stri-

smooth muscle cells, may not reproduce for many

lium of the gut. Many other cells, however, such as

marrow, the germinal layers of the skin, and the epithe-

time, such as the blood-forming cells of the bone

We know that certain cells grow and reproduce all the

Control of Cell Growth and 

each other.

pinches in two, midway between the two nuclei. This is

present in the cytoplasm. Shortly thereafter, the cell

set of chromosomes. This membrane is formed from

pletely apart. Then the mitotic apparatus dissolutes,

), the

In telophase (see Figure 3–13

Telophase.

chromosomes.

separated, forming two separate sets of 46 

at the centromere. All 46 pairs of chromatids are 

), the

During this phase (see Figure 3–13

of the mitotic spindle.

center of the cell, lining up to form the 

each other. Simultaneously, the chromatids are pulled

spines and, using a stepping action as in muscle,

called “motor molecules,” perhaps composed of the

actually push each other away. There is reason to

digitate with each other to form the mitotic spindle,

tubular spines from the two asters, where they inter-

apart. This is believed to occur because the micro-

), the

During metaphase (see Figure 3–13

its partner toward the opposite pole.

still bound to each other; the tubules then pull one

at the centromeres, where the paired chromatids are

the nuclear envelope. At the same time, multiple

During this stage (see Figure 3–13

condensed into well-defined chromosomes.

forming, the chromosomes of the nucleus (which in

While the spindle is

A, B,

shown in Figure 3–13

prophase,

The first stage of mitosis, called 

mitotic apparatus.

spindle,

the two sets of chromatids during mitosis. The complex

each end of the cell. Some of the spines of the aster

aster,

triole pairs, forming a spiny star, called the 

actually pushing them apart. At the same time, other

of centrioles begin to move apart from each other. This

Shortly before mitosis is to take place, the two pairs

centrosome.

triolar material, is called a 

Each pair of centrioles, along with attached pericen-

centrioles of each pair lie at right angles to each other.

structures arranged in the form of a cylinder. The two

in diameter, consisting mainly of nine parallel tubular

the DNA.) Each centriole is a small cylindrical body

during interphase, usually shortly before replication of

like the DNA and chromosomes, were also replicated

other near one pole of the nucleus. (These centrioles,

in Figure 3–13, two pairs of centrioles lie close to each

centrioles.

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

39

around the small structures called 

As shown

about 0.4 micrometer long and about 0.15 micrometer

is caused by polymerization of protein microtubules
growing between the respective centriole pairs and

microtubules grow radially away from each of the cen-

in

penetrate the nuclear membrane and help separate

of microtubules extending between the two new cen-
triole pairs is called the 

and the entire set of

microtubules plus the two pairs of centrioles is called
the 

Prophase.

is

and C.

interphase consist of loosely coiled strands) become

Prometaphase.

D),

the growing microtubular spines of the aster fragment

microtubules from the aster attach to the chromatids

chromatid of each pair toward one cellular pole and

Metaphase.

E

two asters of the mitotic apparatus are pushed farther

believe that minute contractile protein molecules

muscle protein actin, extend between the respective

actively slide the spines in a reverse direction along

tightly by their attached microtubules to the very

equatorial plate

Anaphase.

F

two chromatids of each chromosome are pulled apart

daughter

One of these sets is pulled toward one

mitotic aster and the other toward the other aster as
the two respective poles of the dividing cell are pushed
still farther apart.

and H

two sets of daughter chromosomes are pushed com-

and a new nuclear membrane develops around each

portions of the endoplasmic reticulum that are already

caused by formation of a contractile ring of micro-
filaments 
composed of actin and probably myosin (the
two contractile proteins of muscle) at the juncture of
the newly developing cells that pinches them off from

Cell Reproduction

cells causes these to grow and reproduce rapidly until

the remaining one eighth will grow and divide until the

for many glandular cells and most cells of the bone

and almost any other tissue except highly differenti-

proper numbers of the different types of cells in 

growth often is controlled by 

that come

from the sublying connective tissue of the gland.

when minute amounts of their own secretions are

could provide a means for negative feedback control
of growth.


background image

genes that control cell growth and cell mitosis. The

tosis in cancer cells.

immune disorders. Some drugs that have been used

Alzheimer’s disease, as well as in cancer and auto-

play a key role in neurodegenerative diseases such as

tissues would shrink or grow excessively. Recent

of new cells in healthy adults. Otherwise, the body’s

however, is precisely balanced with the formation 

are replaced by new cells. Programmed cell death,

in adult humans, billions of cells die each hour in

that are being remodeled during development. Even

digested by neighboring phagocytic cells.

thus dismantles itself, and its remains are rapidly

rapidly breaks down proteins within the cell. The cell

activate other procaspases, triggering a cascade that

complex, but once activated, the enzymes cleave and

. The mechanisms of activation of caspases are

. These are enzymes that are

usually remain healthy.

leakage of its contents occurs, and neighboring cells

disassembly and phagocytosis of the cell before any

sis, however, is an orderly cell death that results in 

inflammation and injury to neighboring cells. Apopto-

Necrotic cells may spill their contents, causing

necrosis.

loss of cell membrane integrity, a process called cell

In contrast to programmed death, cells that die as a

phagocytic cell, such as a macrophage, can attach to

shrink and condense, to disassemble its cytoskeleton,

. This process involves

threat to the organism, they undergo a suicidal 

death. When cells are no longer needed or become a

The 100 trillion cells of the body are members of a

Apoptosis—Programmed 

occur.

ation is still hazy, we know many control mechanisms

Thus, although our understanding of cell differenti-

parts.

affecting another part, and this part affecting still other

ops as a result of such inductions, one part of the body

the eye. Therefore, a large share of the embryo devel-

essentially all the organs of the body.

in the surrounding tissues, causes formation of

and, as a result of 

a focus around which the rest of the embryo develops.

primary organizer

primordial chorda-mesoderm

For instance, the 

in an embryo control differentiation of adjacent cells.

more if all genes were active.

function again. Regardless of the mechanism, mature

group of genes. Therefore, the repressed genes never

ecules. One explanation for this is as follows: It has

densed that they no longer uncoil to form RNA mol-

tron micrographs suggest that some segments of DNA

repression of different genetic operons. In fact, elec-

Therefore, it has become clear that differentiation

structures required in the frog’s body.

which is a well-differentiated cell, carries all the 

result is often the formation of a normal frog. This

which the original ovum nucleus was removed, the

When the nucleus from an intestinal mucosal cell of

cesses follows.

structures and organs. The description of an especially

Cell Differentiation

in turn cause the cell to grow larger.

increased production of RNA and cell proteins, which

larger. It is assumed that this results simply from

it normally does, and the cell grows proportionately

nucleus contains far greater quantities of DNA than 

replication of the DNA continues. In this event, the

spindle and therefore to prevent mitosis, even though

colchicine,

that size. Conversely, it is possible, by use of the chem-

nucleus. If replication of the DNA does not occur, the

entirely by the amount of functioning DNA in the

Introduction to Physiology: The Cell and General Physiology

40

Unit I

Regulation of Cell Size.

Cell size is determined almost

cell grows to a certain size and thereafter remains at

ical 

to prevent formation of the mitotic

A special characteristic of cell growth and cell division
is  cell differentiation, which refers to changes in 
physical and functional properties of cells as they pro-
liferate in the embryo to form the different bodily

interesting experiment that helps explain these pro-

a frog is surgically implanted into a frog ovum from

demonstrates that even the intestinal mucosal cell,

necessary genetic information for development of all

results not from loss of genes but from selective

helixes wound around histone cores become so con-

been supposed that the cellular genome begins at a
certain stage of cell differentiation to produce a regu-
latory  protein that forever after represses a select

human cells produce a maximum of about 8000 to
10,000 proteins rather than the potential 30,000 or

Embryological experiments show that certain cells

is called

the 

of the embryo because it forms

It differentiates into a mesodermal axis that contains
segmentally arranged somites

induc-

tions

Another instance of induction occurs when the

developing eye vesicles come in contact with the ecto-
derm of the head and cause the ectoderm to thicken
into a lens plate that folds inward to form the lens of

by which differentiation could

Cell Death

highly organized community in which the total number
of cells is regulated not only by controlling the rate of
cell division but also by controlling the rate of cell

pro-

grammed cell death, or apoptosis
a specific proteolytic cascade that causes the cell to

and to alter its cell surface so that a neighboring

the cell membrane and digest the cell.

result of an acute injury usually swell and burst due to

Apoptosis is initiated by activation of a family of

proteases called caspases
synthesized and stored in the cell as inactive procas-
pases

A tremendous amount of apoptosis occurs in tissues

tissues such as the intestine and bone marrow and 

studies suggest that abnormalities of apoptosis may

successfully for chemotherapy appear to induce apop-

Cancer

Cancer is caused in all or almost all instances by muta-
tion 
or by some other abnormal activation of cellular


background image

by day, cancer cells soon demand essentially all the

proliferate indefinitely, their number multiplying day

tissues for nutrients. Because cancer cells continue to

usually is simple. Cancer tissue competes with normal

The answer to this question

to grow into the cancer, thus supplying the nutrients

new cancerous growths. (3) Some cancers also produce

through the body, where they form nidi for numerous

enter the blood stream, and to be transported all

they have a tendency to wander through the tissues, to

sive to one another than are normal cells. Therefore,

normal cells. (2) Cancer cells often are far less adhe-

usual cellular growth limits; the reason for this is that

are the following: (1) The cancer cell does not respect

The major dif-

cancer.

itself into the animal cell genome, leading to

from the RNA. The transcribed DNA then inserts

that causes DNA to be transcribed

cancer. In the case of RNA viruses, some of these

of DNA viruses, the DNA strand of the virus can

This usually results in one of two ways. In the case

cause some kinds of cancer, including leukemia.

5. In laboratory animals, certain types of viruses can

cancer begins to grow.

genome. Therefore, far fewer additional mutations

cancer, it is presumed that one or more cancerous

more mutations before cancer occurs. In those

to cancer. This results from the fact that

4. In many families, there is a strong 

the cells. The more rapid the mitosis, the greater

tract by some types of food. The damage to 

also can lead to cancer, such as

deaths.

They cause about one quarter of all cancer 

number of deaths are those in cigarette smoke.

The

carcinogens.

predisposition to cancer. Chemical substances that

substances, if unprotected, have a special

derivatives are likely to cause cancer, so that

high propensity for causing mutations. It was

DNA strands, thus causing many mutations.

can predispose individuals to cancer. Ions formed

radioactive substances, and even ultraviolet light

x-rays, gamma rays, and particle radiation from

1. It is well known that 

certain chemical, physical, or biological factors, includ-

However, the probability of mutations can be

occurrence.

tions to take place, so we can suppose that a large

Thus, chance alone is all that is required for muta-

characteristics.

cellular precautions, probably one newly formed cell

is allowed to proceed. Yet, despite all these inherited

any abnormal DNA strand before the mitotic process

replicated in each cell before mitosis can take place,

precision with which DNA chromosomal strands are

mutant cancerous cells? The answer is the incredible

each year in humans, a better question might be, Why

form the needed blood vessels.

reproduction of a cell line, but no cancer occurs

For instance, one such gene might promote rapid

genes are required simultaneously to cause a cancer.

Fourth, usually several different activated onco-

as fivefold.

ability of a cancer’s developing is multiplied as much

drugs after kidney or heart transplantation, the prob-

pressed, such as in those taking immunosuppressant

cells, destroying them. In support of this is the fact 

sitized lymphocytes that react against the cancerous

immune system, causing it to form antibodies or sen-

altered genes, and these proteins activate the body’s

the following way: Most mutated cells form abnormal

system before they grow into a cancer. This occurs in

often, if not usually, destroyed by the body’s immune

Third, those cells that are potentially cancerous are

cancerous, because even most mutated cells still 

bility than normal cells and simply die. Second, only 

this. First, most mutated cells have less survival capa-

body ever lead to cancer. There are several reasons for

activation of oncogenes that lead to cancer.

fore, loss of or inactivation of antioncogenes can allow

suppress the activation of specific oncogenes. There-

antioncogenes,

As many as 100

oncogenes.

Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

Chapter 3

41

abnormal genes are called 
different oncogenes have been discovered.

Also present in all cells are 

which

Only a minute fraction of the cells that mutate in the

a few of the mutated cells that do survive become 

have normal feedback controls that prevent excessive
growth.

proteins within their cell bodies because of their

that in people whose immune systems have been sup-

because there is not a simultaneous mutant gene to

But what is it that causes the altered genes? Con-

sidering that many trillions of new cells are formed

is it that all of us do not develop millions or billions of

and also the proofreading process that cuts and repairs

in every few million still has significant mutant 

number of cancers are merely the result of an unlucky

increased manyfold when a person is exposed to

ing the following:

ionizing radiation, such as 

in tissue cells under the influence of such
radiation are highly reactive and can rupture

2. Chemical substances of certain types also have a

discovered long ago that various aniline dye

workers in chemical plants producing such

can cause mutation are called 
carcinogens that currently cause the greatest

3. Physical irritants

continued abrasion of the linings of the intestinal

the tissues leads to rapid mitotic replacement of

the chance for mutation.

hereditary

tendency
most cancers require not one mutation but two or

families that are particularly predisposed to

genes are already mutated in the inherited

must take place in such family members before a

insert itself directly into one of the chromosomes
and thereby cause a mutation that leads to 

carry with them an enzyme called reverse
transcriptase

Invasive Characteristic of the Cancer Cell.

ferences between the cancer cell and the normal cell

these cells presumably do not require all the same
growth factors that are necessary to cause growth of

angiogenic factors that cause many new blood vessels

required for cancer growth.

Why Do Cancer Cells Kill?


background image

Elsevier Science, 2002.

Pollard TD, Earnshaw WC: Cell Biology. Philadelphia:

disease therapy: past and future. Nat Med 10:135, 2004.

Nabel GJ: Genetic, cellular and immune approaches to

Lewin B: Genes IV. Oxford: Oxford University Press, 2000.

evolution. Science 303:1626, 2004.

Kazazian HH Jr: Mobile elements: drivers of genome 

Physiol Sci 18:7, 2003.

toward the cell periphery: a guided tour for mRNAs. News

Jockusch BM, Hüttelmaier S, Illenberger S: From the nucleus

Annu Rev Med 48:35, 1997.

Hall JG: Genomic imprinting: nature and clinical relevance.

II transcription machinery. Nat Struct Mol Biol 11:394,

Hahn S: Structure and mechanism of the RNA polymerase

tivity. Int J Oncol 24:1039, 2004.

implications for DNA damage signaling and drug sensi-

Fedier A, Fink D: Mutations in DNA mismatch repair genes:

Cullen BR: Nuclear RNA export. J Cell Sci 116:587, 2003.

FASEB J 17:1195, 2003.

DNA damage: mechanisms, mutation, and disease.

Cooke MS, Evans MD, Dizdaroglu M, Lunec J: Oxidative

N Y Acad Sci 1002:56, 2003.

mediated RNA interference (RNAi) in human cells. Ann

Caplen NJ, Mousses S: Short interfering RNA (siRNA)-

J Med 349:969, 2003.

Burke W: Genomics as a probe for disease biology. N Engl

Matters of Life and Death. London: Chapman & Hall,

Bowen ID, Bowen SM, Jones AH: Mitosis and Apoptosis:

cancer. Nat Genet 33(Suppl):238, 2003.

Balmain A, Gray J, Ponder B: The genetics and genomics of

expression. Physiol Rev 81:1269, 2001.

Aranda A, Pascal A: Nuclear hormone receptors and gene

the Cell. New York: Garland Science, 2002.

Alberts B, Johnson A, Lewis J, et al: Molecular Biology of

of the body. As a result, normal tissues gradually suffer

Introduction to Physiology: The Cell and General Physiology

42

Unit I

nutrition available to the body or to an essential part

nutritive death.

References

1998.

2004.




رفعت المحاضرة من قبل: Mostafa Altae
المشاهدات: لقد قام 6 أعضاء و 192 زائراً بقراءة هذه المحاضرة








تسجيل دخول

أو
عبر الحساب الاعتيادي
الرجاء كتابة البريد الالكتروني بشكل صحيح
الرجاء كتابة كلمة المرور
لست عضواً في موقع محاضراتي؟
اضغط هنا للتسجيل