Methionine, cysteine and branched chain amino acids

SULFUR CONTAINING AMINO ACIDS

1. Sulfur Containing Amino Acids
Methionine (MET) M
Cysteine (CYS) C

2. Methionine
Methionine is an essential
glucogenic amino acid
containing sulfur.
The sulfur is bound by
thioester linkage (not freely
detachable)
Degradation of methionine results in the synthesis of cysteine.
Methionine is used to generate active methionine or S-
adenosyl methionine (SAM).
SAM is used to transfer methyl groups to other acceptors.

4. Adenosyl transferase
Methyl transferase
hydrolase

5. CYSTATHIONASE
Succinyl-CoA
Synthesis of
cysteine
gluconeogenesis

7. Transmethylation reactions
•Methionine plays an important role in transmethylation
reactions.
•SAM also known as active methionine serves as the one
methyl donor.
Refer to
Vasudaven for a
list of other
transmethylation
reactions

8. Cysteine
Cysteine is a nonessential glucogenic amino acid.
Cysteine is present in large quantities in keratin
where it forms disulfide bonds.
Cysteine is also present in certain types of urinary
calculi.
Cysteine calculi

9. Sources and Synthesis
Formed from methionine.
CYSTATHIONE β SYNTHASE
CYSTATHIONASE
PLP

11. Degradation of Cysteine
•Cysteine undergoes transamination:
•Cysteine on decarboxylation:
Cysteine
CO
2
b-mercaptoethenolamine
CoA synthesis
Cysteine
b-mercaptopyruvate
TRANSAMINASE
Glutamatea-ketoglutarate
Pyruvate
H
2
S

12. Metabolic Functions of Cysteine
•Cysteine is essential for the formation of glutathione.
•Cysteine is used to synthesize taurine which in turn is
used to conjugate bile acids.
•Cysteine residues in polypeptides are involved in the
formation of disulphide bridges. E.g., insulin
s
s

13. Glutathione
Glutathione is gamma glutamyl cysteinyl glycine.
Glutathione (abbreviated GSH) is a tripeptide
composed of glutamate, cysteine and glycine that has
numerous important functions within cells.
GSH

14. Synthesis
2 molecules of ATP are required
for the synthesis of one molecule
of glutathione.

15. Functions of Glutathione
1.Amino acid transport. g glutamyl cycle (Meister’s
cycle)
2.Coenzyme role in reduction reactions.
2GSH GS-SG + 2H
+

16. •Activation of enzymes - GSH helps to stabilize –
SH groups in the active site of enzymes
•RBC membrane integrity – hydrogen peroxide
formed in the RBCs which damages membranes
is detoxified by GSH
•Met-hemoglobin – GSH helps to reduce
methemoglobin (ferric state) to normal Hb
(ferrous state)
•Conjugation for detoxification – GSH helps in
detoxification of several compounds by
transferring the cysteinyl group to them. This
reaction is catalyzed by glutathione S-transferase

17. Cystinuria
Autosomal recessive inborn error of metabolism
Chief abnormalities excretion of cystine and to a lesser
extent ornithine, lysine and arginine (COAL).
Abnormality : basic amino acid transporter present in
the kidney tubules and intestine
Signs and symptoms:
Crystalluria (occurs in acidic pH), obstructive
uropathy (urinary stones), stasis & secondary
infection.....
Cyanide-nitroprusside test is the screening test.

18. Cystinosis
•Familial disorder associated with
widespread deposition of cystine crystals
in lysosomes.
•Autosomal recessive abnormality in the
transport of cysteine out of the
lysosomes.
•Cysteine accumulates in kidney, liver
spleen, bone marrow, cornea and lymph
nodes.

19. •Three forms of presentation:
–Infantile: renal failure in first decade
–Juvenile: renal failure in second decade
–Adult type: benign, kidney is spared, deposition
of cystine is mainly seen in the cornea

20. Homocystinurias
A group of genetic disorders associated with the the
excretion of homocystine in urine.
All are autosomal recessive conditions.
An increase in the serum homocystine levels
(hyperhomocysteinemia) elevates the risk of
development of coronary artery diseases.

21. Cystathionine
Cystathionine β synthase
Homocystinuria
type 1
Methionine synthase
Homocystinuria
type 2
Methylene THFA reductase
Homocystinuria
type 3

22. •Characterized by mental retardation, ectopia
lentis, intravascular thrombosis, renal
calculi, accelerated atheroschlerosis and
premature death, usually due to
cardiovascular complications
•High levels of homocysteine
(hyperhomocysteinemia) may also be
acquired.
–Vitamin deficiency- vit B12, vit B6, folic acid
–Drug induced – folate antagonists (like
methotrexate)

23. Branched chain amino acids
Valine
Leucine
Isoleucine

24. •They are essential amino acids
•Valine is glucogenic
•Leucine is ketogenic
•Isoleucine is glucogenic and ketogenic
•They serve as an important alternate source
of energy to the brain especially in
starvation

25. TRANSAMINASE
α-KETOACID
DEHYDROGENASE
Maple syrup
urine disease