5 of 7.

Metabolism of Proteins & Amino

Acids
• Digestion of Proteins & Absorption of Amino Acids
• Transamination & Deamination of Amino Acids and urea cycle
• Specialized products formed from Amino Acids
 Recommended Material
• Harper’s Biochemistry by Robbert K. Murray, Daryl K. Granner, Peter A. Mayes, Victor W.
Rodwell, Latest Ed.

• Lippincott’s Illustrated Review of Biochemistry by Pamela C. Champe and Richard A. Harvey,

Latest Ed.

• Practical Clinical Biochemistry by Varley.

• Textbook of Biochemistry by Devlin, 5th Ed.

• Textbook of Medical BiochemistryVol-I and II by M.A. Hashmi. Biochemistry by Stryer, Lubert,

Latest Ed
Digestion of Proteins & Absorption of Amino Acids
 Digestion
and
Absorption
of
Proteins

Biochemistry for Medics 4

 Digestion of dietary proteins

Digestion: The disintegration of complex nutrients into simple, soluble and assimilable form

Food Nitrogen: Mostly from proteins

Absorption of proteins: Proteins are too large to be absorbed.

proteins are hydrolyzed to amino acids by enzymes, which can be easily absorbed

Biochemistry for Medics 5

• Where are proteolytic enzymes produced?

• stomach
• pancreas
• small intestine

6
 Characteristics of proteolytic enzymes

1)They are hydrolases

2)Secreted in the zymogen (Inactive) form

converted to active form in the intestinal lumen
The active site of the enzyme is masked by a small region of the peptide
chain that is removed by hydrolysis of a specific peptide bond
3) They may be Exopeptidases or Endopeptidases

Exopeptidases catalyze the hydrolysis of peptide bonds, one at a time, from

the ends of peptides

Endopeptidases hydrolyze peptide bonds between specific amino acids

throughout the molecule

Biochemistry for Medics 7

 Digestion in the oral cavity

There are no proteolytic enzymes present in the saliva

The function of the saliva is to lubricate the food

This helps in making food soluble for the action of proteolytic enzymes

Biochemistry for Medics 8

 Digestion by gastric juice
Gastric juice contains

1. Acids
HCL
2. Proteolytic enzymes
Pepsin
Rennin
Gelatinase
3. Hormone
Gastrin
Biochemistry for Medics 9
 Functions of HCL
• Denatures proteins

• Activation of inactive proteolytic enzymes

• Bacteriostatic in action

10
 Pepsin
1. Secreted in the form of pepsinogen

2. Activated by HCL and pepsin itself (Autocatalysis)

3. Acid stable endopeptidase, optimum pH lies between 1.6-2.5 ;

becomes inactive if the pH is > 5.0

4. Breaks bond between hydrophobic and aromatic amino acids like

Phenyl Alanine, Tyrosine and Tryptophan
11
Biochemistry for Medics
 Rennin(chymosin)

1. Present in infants but absent in adult gastric juice

2. Secreted as pro-rennin
3. Optimum pH 4.0
4. Action is similar to pepsin
5. Acts on casein of milk and is involved in the curdling of milk

So that the liquid milk becomes semisolid and hence reduce its quick flow

Biochemistry for Medics 12

 Gelatinase

1. Secreted in zymogen form

2. Acid-stable
3. Activated in the presence of HCL
4. Acts on Gelatin to hydrolyze it to short peptides

Biochemistry for Medics 13

 Gastrin
• A peptide hormone

• Stimulates secretion of gastric acid (HCl)

 Digestion by Pancreatic Juice

1. All the enzymes are active only in the alkaline medium

2. Alkalinity is provided by Bile juice and bicarbonates present in pancreatic juice

The proteolytic enzymes present in pancreatic juice are

-Trypsin (Basic)
-Chymotrypsin (Large Aromatic)
-Elastase
-Collagenase
-Carboxypeptidases 15
Biochemistry for Medics
 Trypsin

Inactive form: (Trypsinogen)by the intestinal mucosa ) and by

Function:
activation of
Chymotrypsinogen to chymotrypsin
pro-elastase to elastase
fibrinogen to fibrin
weak action on casein
Cleaves at carboxyl end of Lysin or Arginine i.e. Basic amino acids

Biochemistry for Medics 16

 Chymotrypsin

1. Activated by Trypsin and Chymotrypsin itself

2. Cleaves peptide bonds at carboxyl end of aromatic amino acids

3. Can hydrolyze milk protein

Biochemistry for Medics 17

 Carboxy-peptidases
Two types of Carboxypeptidase are there
Carboxypeptidase A
a. Metalloenzyme , contains Zinc
b. Activation brought about by Trypsin and auto catalytically by itself
c. Exopeptidase, Hydrolyzes the terminal peptide bond connected to an end
amino acid (Aromatic) bearing free carboxyl group
Carboxypeptidase B
a. Also an Exopeptidase
b. Hydrolyzes terminal peptide bonds connected by Basic amino acids
Biochemistry for Medics 18
 Elastase and Collagenase

Elastase-

Activated by Trypsin

acts on neutral aliphatic amino acids- Alanine, Glycine, Serine etc.

Collagenase-

Acts on Collagen

Biochemistry for Medics 19

 Digestion by intestinal Juice

Enzymes present in intestinal juice are

- Enterokinase

- Amino peptidases

- Prolidase

- Di and Tri peptidases

Biochemistry for Medics 20

 Functions of the Intestinal enzymes

Enterokinase - required for activation of Trypsin, also called Enteropeptidase

Amino peptidases – are exopeptidases, remove the amino acid one by one from amino
terminal end of peptide chains

Prolidase - also an exopeptidase, removes proline residues from terminal end of peptide
chains.
Biochemistry for Medics 21
 Functions of Intestinal enzyme(Contd.)

Di and Tripeptidases –
Digestion of di and tri peptides is brought about by di and tri peptidases

Tripeptidases convert tripeptides into a dipeptide and a free amino acid

Dipeptidases convert dipeptides to free amino acids

Biochemistry for Medics 22

 Diseases associated with digestion of proteins

Acute Pancreatitis
Premature activation of pancreatic proteolytic enzymes in the pancreas itself
It causes digestion of the secretory mucosa causing Acute pancreatitis
It is a life-threatening condition

Biochemistry for Medics 23

 Steatorrhea

In conditions of deficient pancreatic secretions like

cystic Fibrosis, chronic pancreatitis or surgical removal of pancreas
the digestion and absorption of fats and proteins is left incomplete
with the resultant appearance of lipids and undigested proteins in the feces.
This condition is called Steatorrhea

Biochemistry for Medics 24

Absorption of amino acids

25
 Absorption of amino acids
Site of Absorption-
Oligopeptides
duodenum
proximal Jejunum
Amino acids
distal jejunum
ileum

Biochemistry for Medics 26

 Mechanism of Absorption of Oligopeptides

Absorbed by active transport

Intracellular peptidases hydrolyze them to amino acids

Hydrolysis is rapid to keep peptide concentration low in the cell

Transport mechanism is independent of L- amino acids

Biochemistry for Medics 27

 Mechanism of Absorption of amino acids

Natural L-amino acids: active transport

D- amino acids: simple diffusion

Other molecules required for active transport

Vitamin B6
ATP
A carrier protein (mainly Na+ dependent)
Different carrier proteins are there specific for different amino acids

Biochemistry for Medics 28

 Clinical Significance

Cystinuria
Common transporter for cystine, ornithine, arginine and lysine(COAL) is present in gut & renal tubules
Deficiency of transporter results in loss of these amino acids in the feces and urine

Hart- Nup Disease

There is deficiency of transporter for tryptophan and neutral amino acid
No absorption of tryptophan takes place
Tryptophan deficiency produces neurological and skin manifestation

29
 Food Allergies
Food allergies are due to absorption of undigested peptides by pinocytosis.
The immune response may be local or systemic
Examples-
Nut allergies
Fish allergies
Egg allergies

Clinical Manifestations may be due to local damage in the intestine in the form of
nausea, vomiting, diarrhea, abdominal cramps

Systemic manifestations
cutaneous rashes, running nose, facial flushing, broncho-constriction or
anaphylactic shock in severe cases
Biochemistry for Medics 30
Transamination & Deamination of Amino Acids and urea cycle
 CONTENT
• TRANSDEAMINATION
• TRANSAMINATION
• DEAMINATION
 TRANSDEAMINATION
The amino group of amino acids is released by a coupled reaction called

TRANSDEAMINATION

Transamination
Deamination
 Transamination
• Transamination  is a chemical reaction between two molecules

• One is an amino acid, which contains an amine (NH2) group

• The other is a keto acid, which contains a keto (=O) group

• NH2 group on one molecule is exchanged with the =O group on the other

• The amino acid becomes a keto acid, and the keto acid becomes an amino acid

• Enzymes: Transaminases or Aminotransferases
Reaction
General scheme of transamination
R CH COOH + HOOC C CH2CH2COOH
NH2 O
aminokyselina
amino acid 2-oxoglutarate
2-oxoglutarát

aminotransferase
aminotransferasa
pyridoxalfosfát
pyridoxal phosphate

R C COOH + HOOC CH CH2CH2COOH

O NH2

2-oxokyselina
2-oxo acid glutamát
glutamate
36
 DEAMINATION
• Deamination is the removal of an amine group from a molecule. 

• Enzymes: Deaminases

• In the human body, deamination takes place primarily in the liver

• Deamination is the process by which amino acids are broken down if there is

an excess of protein intake
• The amino group is removed from the amino acid and converted to ammonia
 Types of Deamination

• Four types of deamination

•- reduction
•- hydrolytic
•- intramolecular
•- oxidative (the most important for higher animals)
 Reductive deamination

H
___ ___

H
R ___ C ___ COOH

___
NH2 H
 Hydrolytic deamination

H
___ ___

H
R ___ C ___ COOH

___
NH2 OH
 Intramolecular deamination

H H
___

___ ___
___ ___
R C ___ C ___ COOH
___

H
NH2
 Oxidative deamination

 the amine functional group is removed as ammonia

 The amine functional group is replaced by the ketone group
 The ammonia eventually goes into the urea cycle
 Oxidative deamination occurs primarily on glutamic acid
 Oxidative deamination

H
___ ___

R ___ C ___ COOH NAD

H OH
H NH
 Oxidative deamination

___
R ___ C ___ COOH NAD H
___

H OH
NH
 Oxidative deamination

___
R ___ C ___ COOH NAD H
___
___

H OH
NH
 Oxidative deamination

O H

___
R ___ C ___ COOH NAD H
___
___

NH
H H
 Oxidative deamination

O H
___ ___
___

___
R ___ C ___ COOH NAD H
___ ____

NH
_ _

H H
Urea Cycle
 Urea Cycle
• Also known as “ornithine cycle”

• Produces urea ((NH2)2CO) from ammonia (NH3)

• In mammals, the urea cycle takes place

• primarily in the liver
• to a lesser extent in the kidney
 Urea Cycle (cont.…)
• Urea synthesis: in liver

• From liver into blood stream

• From blood into kidneys

• Excretion in the urine.

Liver Blood Kidneys Urine

 Urea Cycle (cont.…)
• Ammonia is toxic to body

• Therefore, needs to be detoxified by urea cycle into urea

Specialized products formed from Amino Acids
Self Study
CONVERSION OF AMINO
ACIDS TO SPECIALIZED
PRODUCTS
a-nitrogen atom of amino acids is a primary
source for many nitrogenous compounds For
example:

Heme
Purines and pyrimidines
Hormones
Neurotransmitters
Biologically active peptides
Glycine
 Glycine
Glycine is used for heme, purine and creatin synthesis
a carbon and nitrogen atoms of glycine are used for synthesis of
porphyrine, prosthetic group of heme.

Take over: http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/heme.htm

 Synthesis of glutathione (GSH)

1. Drug detoxification: Glutathione serves as a reductant; is conjugated to drugs to make them more water soluble (detoxification).
2. Peroxides reduction: Reduces peroxides formed during oxygen transport. The resulting oxidized form of GSH consists of two molecules
disulfide bonded together (abbreviated GSSG).
3. Amino acid transport through cell membrane: Is involved in amino acid transport across cell membranes (the g-glutamyl cycle).
4. Cofactor of enzymes: Serves as a cofactor for some enzymatic reactions and as an aid in the rearrangement of protein disulfide bonds.

Take over: http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/MB1index.html

Tyrosine
 Tyrosine
The majority of tyrosine that does not get incorporated into proteins is used for

•Energy production
•catecholamines production

The catecholamine are neurotransmitters

e.g. dopamine, norepinephrine and epinephrine.

•Tyrosine is transported into catecholamine-secreting neurons and adrenal medullary cells where
catecholamine synthesis takes place.
 Synthesis of the Catecholamines from Tyrosine

1. Tyrosine hydroxylase requires tetrahydrobiopterin as

cofactor.
2. The hydroxylation reaction generates DOPA. (3,4-
dihydrophenylalanine)
3. DOPA decarboxylase converts DOPA to dopamine.
4. Dopamine b-hydroxylase converts dopamine to
norepinephrine.
5. Phenylethanolamine N-methyltransferase converts
norepinephrine to epinephrine.

Take over: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html

Glutamic Acid
 g-aminobutyric acid (GABA)

 Inhibitory neurotransmitter (CNS).

 Directly regulates muscle tone.
 Its lack leads to convulsions, epilepsia.
 Involved in mechanism of memory.
Tryptophan
 Tryptophan

Tryptopan serves as the precursor for the synthesis of serotonin and melatonin

1. Hydroxylation reaction (tryptophan-5-monooxygenase)

2. Decarboxylation (aromatic L-amino acid decarboxylase)
3. Acetylation (serotonin N-acetylase)
4. Conversion to melatonin (hydroxyindole-O-methyltransferase).

Take of textbook: D. L. Nelson, M. M. Cox: Lehninger Principle of Biochemistry. Fourt Deition.

 Serotonin and melatonin
Serotonin is present at highest concentrations in platelets and in the gastrointestinal tract.
Lesser amounts are found in the brain and the retina.

• Serotonin containing neurons have their cell bodies in the midline raphe nuclei of the brain stem.
• Proportions of neurons are projected to the hypothalamus, the limbic system, the neocortex and the spinal
cord.
• The released serotonin is recaptured by an active reuptake mechanism.
• Antidepressant, Prozac is to inhibit this reuptake process.

• Synthesis and secretion of melatonin increases during the dark period of the day.
• Concentration maintained at a low level during daylight hours.
Arginine
 Polyamine Biosynthesis
1. Conversion of arginine to ornithine.
2. Ornithine to putrescine (ornithine decarboxylase).
3. Putrescine to spermidine (spermidine synthase, putrescine
aminotransferase).
4. Spermidine to spermine(Spermidine aminotranspherase).
SAM – s-adenosyl methionine is donor of methyl group

• Polyamines are highly cationic

• tend to bind nucleic acids
• Participates in DNA synthesis
• Modulates ion channels
• As Growth factors

Take over: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html

Histidine
 Histidine

Carnosine is the dipeptide of the amino

acids b-alanine and histidine.
Carnosine is highly concentrated in muscle and
brain tissues.

• Scavenger of ROS (radical oxygen species).

• Protection of the peroxidation of cell.
• Possibly improving Alzheimer´s disease

Carnosine
 Histamine
Histamine is derived from the decarboxylation of the amino
acid histidine.

a neurotransmitter.

Causes several allergic symptoms. 

1) It contributes to an inflammatory response. 

2) It causes constriction of smooth muscle.
3) Is cause second type of allergic response
4) one of the major causes for asthma
Amino acid Synthesis
Glycine Heme, Purine,
Creatine,
Glutathione
Tyrosine Energy,
Catecholamines
Glutamic acid Gama
Aminobutyric acid
Tryptophan Serotonin,
melatonin
Arginine Polyamine Ornithin,
putriscine,
Spermidine,
Spermine
Histidine Carnosine,
Histamine
Thank You