Protein

Metabolism
By
Dr. Mustafa Kahtan Al-Bayaty
 Proteins
• Proteins are the primary constituents of the body and
they may be structural or functional.

• A regular and adequate supply of protein in diet is

essential for cell integrity and function.

• Dietary proteins are the primary sources of the

nitrogen that is metabolized by the body.
 Functions of dietary proteins
1. Their constituent amino acids are used for synthesis of the
body’s proteins.

2. The carbon skeletons of the amino acids can be oxidized to

yield energy.

3. Their carbon and nitrogen atoms may be used to synthesize

other nitrogen containing cellular constituents as well as
many non-nitrogen containing metabolites.
 Digestion and absorption of
proteins
• Proteolytic enzymes (also called proteases) break down dietary proteins
into their constituent amino acids.

• Proteases are produced by three different organs:

1. The stomach.

2. The pancreas.

3. The small intestine.

 Digestion in Mouth

•There is no protein digestion in the mouth.

•The digestion of proteins starts in the

stomach.
 Digestion in Stomach
• When protein enters the stomach, it stimulates the secretion of the
hormone gastrin.

• Gastrin then stimulates the release of gastric juice.

• Gastric juice contains:

1. Hydrochloric acid.
2. Pepsinogen (zymogen).
3. Rennin (in infants).
 Protein in
stomach

Stimulates

Gastrin release

Stimulates

Release of
gastric juice
Contains

Hydrochloric Rennin (in

Pepsinogen
acid infants)
 Hydrochloric acid (HCl)

Functions of hydrochloric acid are:

1. HCl denatures proteins making their internal peptide

bonds more accessible to subsequent hydrolysis by
proteases.

2. Provides an acidic environment for the action of

pepsin.
 Pepsin
• It is secreted as the proenzyme pepsinogen, an inactive form.

• It is converted into active pepsin in the gastric juice by:

1. Hydrochloric acid.
2. The enzymatic action of pepsin itself.

Pepsin function:
• it cleaves long polypeptide chains into a mixture of smaller peptides and
some free amino acids.
 Pepsinogen
(Inactive)

HCl (pH 1.5 – 2.5) Activation of

pepsinogen
Pepsin
(Active)

Smaller peptides
Long polypeptide Pepsin cleaves
chains of proteins
+
Free amino acids

Action of pepsin
 Renni
n
• It is important in the digestive processes of infants. It is absent in adults.

Rennin function:

• The function or action of rennin is to clot milk.

• This is accomplished by the slight hydrolysis of the casein of milk to

produce paracasein, which coagulates in the presence of calcium ions,
resulting in an insoluble calcium-paracaseinate curd. Calcium
paracaseinate is then acted on by pepsin.
 Action of Rennin

Rennin Ca2+ Ca-paracaseinate

Casein Paracasein
(Insoluble curd)

The purpose of this reaction is to convert milk into a more

solid form to prevent the rapid passage of milk from the
stomach of infants.
 Digestion in small intestine
Digestion of proteins in the small intestine occurs in two
phases:

1. The first phase (1st phase) is digestion by pancreatic

enzymes.

2. The second phase (2nd phase) is digestion by intestinal

enzymes.
 Digestion in
small intestine

1st phase 2nd phase

Digestion by Digestion by
pancreatic enzymes intestinal enzymes

Endopeptidase Exopeptidase Aminopeptidase Dipeptidase

1. Trypsin.
1. Carboxypeptidase.
2. Chymotrypsin.
2. Aminopeptidase.
3. Elastase.
 Digestion in
small intestine

1st phase 2nd phase

Digestion by Digestion by
pancreatic enzymes intestinal enzymes

1. Trypsin.
2. Chymotrypsin. 1. Aminopeptidase.
3. Elastase. 2. Dipeptidase.
4. Carboxypeptidase.
Activation of pancreatic proenzymes
• After the 2nd phase of digestion by intestinal enzymes,
all ingested protein is converted into free amino acids.

• The hydrolysis of most proteins is thus completed to

their constituent amino acids which are then ready for
absorption into the blood.
 Protein turnover
• Protein turnover is the process of hydrolysis and re-
synthesis of body proteins.

• In healthy adults, the total amount of protein in the body

remains constant because the rate of protein synthesis is
just sufficient to replace the protein that is degraded.

• The turnover is high in infancy and decreases with age

advance.
 Nitrogen balance
• Nitrogen balance is the relationship between the nitrogen intake (in
the form of protein) and nitrogen excretion.

• There are three situations of nitrogen balance:

1. Nitrogen equilibrium.

2. Positive nitrogen balance.

3. Negative nitrogen balance.

 Nitrogen Equilibrium

• In normal adults, nitrogen intake is equal to nitrogen

excretion. The subject is said to be in nitrogen
equilibrium or balance.

• In this situation, the rate of body protein synthesis is

equal to the rate of protein degradation.
 Positive Nitrogen Balance

• In this situation, nitrogen intake > nitrogen excretion,

i.e. intake of nitrogen is more than excretion.

• It shows that nitrogen is retained in the body.

• This occurs in growing infants and pregnant women.

 Negative Nitrogen Balance
• In this situation, nitrogen intake < nitrogen excretion, i.e.
nitrogen output exceeds input.

• This occurs during serious illness and major injury and

trauma, in advanced cancer and following failure to ingest
adequate or sufficient high quality protein, e.g. in
kwashiorkor and marasmus.

• If the situation is prolonged, it will ultimately lead to death.

 Catabolism of amino acids
The complete catabolism of amino acids includes following stages:

1. The removal of α-amino group in the form of ammonia by the following

reactions:

• Transamination (by aminotransferase also called transaminase).

• Deamination.

2. Disposal of ammonia in the form of urea in the liver by reactions of the urea cycle.

3. Disposal (catabolism) of the remaining carbon skeleton of amino acid to carbon

dioxide and water by reactions of TCA cycle.
 Formation of ammonia

Ammonia is formed from amino acids by

a combination of two reactions;

transamination and deamination.

1. Transamination: it is the transfer of amino group
from an α-amino acid to α-keto acid.
2. Deamination: it is the removal of the amino group
from an amino acid in the form of ammonia (NH4+).
 Transport of ammonia to the liver
• Since free ammonia is highly toxic, it is never transported in free
form in blood.

• Two mechanisms are available in humans for the transport of

ammonia from the peripheral tissues to the liver for its ultimate
conversion to urea. These mechanisms are:

1. Transport of ammonia in the form of glutamine.

2. Transport of ammonia in the form of alanine.

 Formation of urea
• Urea is the end product of protein metabolism.

• The nitrogen of amino acids removed in the form of ammonia is

detoxified by converting it to urea.

• Formation of urea by “Kreb’s Henseleit urea cycle” is an ultimate

route for the metabolic disposal of ammonia.

• Urea is produced exclusively by the liver and then is transported

through blood to the kidneys for excretion in the urine.
 Urea cycle
• It is the sequence of reactions involved in the biosynthesis of
urea.

• The cycle involves five enzymes and five steps or reactions.

• The first two reactions take place in the mitochondria while the
remaining reactions take place in the cytosol of the liver.

• In urea cycle, four ATPs are consumed in the synthesis of one urea
molecule.
The general equation describing urea cycle is given
below:

5 steps, 5 enzymes
Ammonia + 4 ATP Urea cycle reactions
Urea
 Significance of urea cycle

• The toxic ammonia is converted into the harmless

nontoxic urea.

• It disposes off two waste products, ammonia and

CO2.
 Blood urea
• Normal range of blood urea for a healthy adult is 20 to 40
mg/dL.

• High protein diet shows increase in level of blood urea

concentration.

• In clinical practice, blood urea level is taken as an indicator of

renal function.

• The term uremia is used to indicate increased blood urea levels.

The causes of high blood urea are subdivided into
three classes:

1. Prerenal uremia.

2. Renal uremia.

3. Postrenal uremia.
Causes of prerenal uremia:

1. High protein diet.

2. Increased protein catabolism, e.g. trauma, surgery,

starvation, diabetes mellitus.

3. Impaired renal perfusion (Renal perfusion refers

to the blood flow that passes through a unit
mass of renal tissue), e.g. cardiac failure.
Causes of renal uremia
• Any cause that leads to reduced glomerular filtration
rate (GFR) and leads to urea retention.

Causes of postrenal uremia

• Any cause of obstruction to urine outflow, e.g. benign
prostatic hypertrophy, malignant stricture or
obstruction e.g. stones.