Protein metabolism
By
Dr. Sahar A. Helmy
Lecturer of Biochemistry
Special pathways for individual amino acids
1- Glycine amino acid
Characters: It is glucogenic, non-essential
Why glycine is nonessential AA?
because it can be formed from threonine and from serine:
Threonine
glycine + acetaldehyde (Irreversible)
Serine
glycine + formaldehyde (reversible)
Why glycine is glucogenic AA?
because it can form pyruvate.
+
Formaldehyde
A. Anabolic reactions of Glycine
A- Glycine enters in the formation of:
creatine
Bile salts
purines
Glycine
porphyrins
glutathione
serine
1.Porphyrins (Hb & Mb):
Glycine + succinyl CoA
-amino--ketoadipic acid
Pyridoxal. P
porphyrins
2.Bile Salts:
Glycine + cholic acid
Glycocholic acid
NaCl or KCl
Na or K glycocholate
(bile salt)
3. Purines:
Carbons 4 and 5 and nitrogen 7 are derived from glycine
4-Serine synthesis
5. Creatine and creatine phosphate of muscles:
•
Creatine synthesis requires glycine, arginine and
methionine.
• Creatine phosphate is the main store of energy in muscle
used for muscle contraction.
• Creatinine is produced either from dephosphorylation of
creatine phosphate or from dehydration of creatine
itself.
• Creatinine is excreted in urine.
-H2O
6. Glutathione(G-SH):
•
It is a tripeptide formed from 3 amino acids (-glutamylcysleinyl-glycine). It is formed in the liver by the help of
ATP.
• Glutathione can exist in 2 forms:
A- Reduced form containing free –SH group (G-SH)
B- Oxidised form (G-S-S-G) containing disulfide linkage.
• Glutathione (G-SH) has the following functions:
1. It protects haemoglobin against oxidation by hydrogen
peroxide:
• Keep iron of Hb in Fe++ state.
• Keep globin in native state.
2.
It protects the red blood cells from haemolysis by
various agents.
3. It maintains the reduced (–SH) group, which is the
active and essential group of many enzymes.
4. It inactivates insulin in the liver by reductive cleaving of
the 2 disulfide linkages of insulin into 2 separate
polypeptide chains.
Insulin glutathione
transhydrogenase
Insulin
2 separate polypeptide chains (inactive insulin)
4GSH
2GS-SG
5. It protects the -cells of pancreas from the degenerative
action of alloxan or dehydroascorbic acid. This protective
action is due to the (–SH) group of glutathione which
reduces alloxan to inactive substance and reduces
dehydroascorbic acid to ascorbic acid.
6. It is a cofactor of maleylacetoacetate isomerase enzyme
in the synthesis of acetoacetate from tyrosine or
phenylalanine.
Maleylacetoacetate
isomerase
Maleylacetoacetate
G–SH
Fumaryl acetoacetate
7. Glutathione in the oxidized form (G–S–S–G) acts as a
hydrogen carrier and so it is considered as a tissue
respiratory enzyme.
G–S–S–G +2H
2G–SH.
-2H
8.Glutathione plays an important role in -glutamyl
cycle (absorption of a.a).
Mechanism of antioxidant function of GSH
• Glutathione is maintained in the reduced form (G–SH) in
red blood cells by the help of a reductase enzyme
needing NADPH+ H+ as a coenzyme.
• In red blood cells, this NADPH+H+ is produced in the first
reaction of HMP-shunt which needs the presence of
glucose -6- phosphate dehydrogenase enzyme : Glucose6-phosphate
Glucose-6-phosphate
Glucose-6-phosphate
Dehydrogenase (G-6-PD)
NADP+
2GSH
6-Phospogluconate
NADPH+H+
GS-SG
Favism and primaquine sensitivity
Congenital
deficiency
of
glucose-6-phosphate
dehydrogenase enzyme, NADPH+H+ is not produced and
as a result glutathione (G-SH) becomes deficient in red
blood cells resulting in increased tendency to haemolysis
especially after the intake of some foods e.g. Fava beans,
or some drugs e.g. sulfa drugs, anti-malaria drugs.
Glycineis in
detoxification
B.B.Glycine
used
in detoxication:
Being conjugated with benzoic acid giving hippuric acid
which is excreted in urine.
Glycine + Benzoic acid (Toxic)
Toxic)
urine
Hippuric acid (Less
C. Catabolic reactions of glycine
• Glycine by oxidative deamination or by transamination
gives glyoxylic acid which by oxidative decarboxylation
gives formic acid.
Primary hyperoxaluria
The overproduction of a substance called oxalate (also
called oxalic acid). In the kidneys, the excess oxalate
combines with calcium to form calcium oxalate, a hard
compound that is the main component of kidney stones.
Deposits of calcium oxalate can lead to kidney damage,
kidney failure, and injury to other organs.
Cause of primary hyperoxaluria:
• Genetic defect leads to loss of specific enzyme and
the normal metabolic pathway is blocked.
• Failure of oxidation of glyoxylic acid to formic acid will
lead to oxidation of glyoxylic acid to oxalic acid which
is excreted in great amounts in urine.
• Congenital absence of glycine transaminase is the
main cause of such disease.
(2) Alanine
• It is non-essential glucogenic amino acid because it can
be formed in the body from pyruvic acid by
transamination with any amino acid e.g. glutamate.
L-glutamic acid+ pyruvic acid
Pyr.P
GPT (ALT)
L-alanine+α-ketoglutaric acid
Protein metabolism
By
Dr. Sahar A. Helmy
Lecturer of Biochemistry
(3) Serine
• It is a non-essential amino acid formed from glycine and
formaldehyde.
• It is glucogenic amino acid giving pyruvic acid and ammonia
by non-oxidative deamination.
+
Formaldehyde
Functions of serine
Serine
Cysteine
phospholipids
phosphoproteins
1- formation of Phospholipids:
Sphigomyelins
Palmityl CoA aldehyde
Cephalins
Serine
Co2
Ethanolamine
Cephalins
3(-CH3)
Choline
Lecithins
2- Formation of phosphoproteins
The phosphate group is usually attached to (–OH) group
of serine or threonine present in phosphoproteins as
caseinogen.
3- Cysteine formation
Cysteine is formed from methionine and serine as follows.
Cystathioninase
(4) Threonine
• It is essential, glucogenic amino acid. It can give glycine
and acetaldehyde in the body
+
Formaldehyde
(5) Tryptophan
•
•
It is essential and both glucogenic and ketogenic amino acid.
It has 3 main pathways:
1- Nicotinic acid pathway.
2- Serotonin and Melatonin pathway.
3- Indole and skatole pathway (putrefaction).
1)Nicotinic acid pathway:
This is the main and most important pathway of tryptophan.
(NAD+)
(NADP+)
(Nicotinamide
ribose
diphosphate)
• Pyridoxal phosphate is necessary as a coenzyme. So vitamin B6
necessary for synthesis of nicotinic acid.
• Nicotinamide formed enters in the formation of coenzymes I, II and
III.
• Tryptophan is both:
 glucogenic because it produces alanine that can form pyruvate.
 ketogenic because it produces acetoacetic acid.
2)Serotonin and Melatonin Pathway:
•Serotonin is a substance stored in platelets, gastrointestinal mucosa
and CNS.
•It is formed from tryptophan as follows:
(Tryptophan hydroxylase)
(Serotonin)
(urine)
• Tryptophan metabolism is greatly deviated to serotonin pathway
in malignant tumors.
Function of serotonin
1- It mediates gut movement.
2- a mood regulator in vertebrate animals
• Abnormal serotonin levels are also associated with problems
such as suicidal tendency, obsessive compulsive disorder, and
anxiety.
• Tryptophan can give melatonin which is secreted by the pineal
body and peripheral nerves.
N-acetylation
N-Acetyl transferase
Serotonin
N-acetylserotonin
HIOMT
Melatonin
• HIOMT: Hydroxyindole O-methyltransferase.
• Melatonin is a hormone used as a sleep aid and in the treatment
of sleep disorders.
3- Indole and skatole pathway:
•
These are produced normally by the action of bacteria in large
intestine on tryptophan. It is an example of putrefaction.
•
Indole and skatole give the foul odour of stool.
•
In case of constipation, Indole is reabsorbed by intestinal mucosa
to be oxidized into indoxyl which reaches liver, conjugated with
sulfuric acid and excreted in urine as indoxyl potassium sulfate
(indican). So indican is one of the abnormal constituents of urine.
-CO2