SULPHUR CONTAINING

AMINO ACIDS

Dr Rakhee Yadav
Associate Professor
Dept of Biochemistry
AIIMS Delhi
Learning objectives

• To enlist Sulphur containing amino acids

• To discuss their metabolism and inter-links with other

biomolecules

• To delineate their physiological and pathological relevance

• To describe disorders related to Sulphur containing amino

acids including their clinical features and management.
 SULPHUR CONTAING AMINO ACIDS
 Thiol/Thio-alcohol/sulphydryl
 Polar
 Forms THIO-ESTER bond with
Acyl groups

Homocysteine

METHIONINE CYSTEINE CYSTINE

Taurine
 METHIONINE
 Essential
 Hydrophobic and non polar, present in the interior of proteins
 Translation initiation amino acid in the proteins
 Glucogenic
 Metabolism of Methionine

1. Utilization in Transmethylation reaction:

 The transfer of methyl group from active Methionine to

an acceptor is known as Transmethylation

 Methionine has to be activated to form

S-Adenosylmethionine (SAM) or active methionine to
donate methyl group

2. Conversion of Methionine to Cysteine

Methionine cycle e sfe
ras
e

nin ran
hio yl t
et nos
M e
ad

Methionine
Methyl
Synthase
transferase
(B12)
Methyl group acceptor Methylated product
Guanidinoacetate Creatine

Norepinephrine Epinephrine

Epinephrine Metanephrine

Ethanolamine Choline

Acetyl serotonin Melatonin

Phosphatidyl ethanolamine Phosphatidyl choline

t-RNA bases Methylated t-RNA bases

Lysine Methyl lysine

 Methionine Regenerated

Homocysteine Pyruvate

serine
Cystathione-β synthase
(B6) H2S+NH3
H2O
H2O NH3 H20
Cystathionine α-Keto butyrate + Cysteine
Cystathionine
γ-lyase Co-ASH + NAD+
NADH+CO2

Propionyl-CoA Succinyl- CoA

Let’s summarise

ate
l
Fo cle nine
hio
cy t
Me cycl
e
 CYSTEINE
 Semi-essential.

 The thiol side chain in cysteine often

participates in enzymatic reactions, as
a nucleophile.

 The thiol is susceptible to oxidation to give

the disulfide derivative Cystine, which serves
an important structural role in
many proteins

 Glucogenic
H20 H2S+NH3
Cysteine Pyruvate
 Metabolic roles of cysteine

Formation of Glutathione

𝜸-glutamyl cysteinyl glycine

Let’s recapitulate functions of Glutathione

• Intracellular reducing agent:

Many enzymes having active –SH groups at active site are
kept in the active form (reduced state) by GLUTATHIONE
• Maintenance of RBC membrane

• Transport of neutral amino acids across

membrane of renal tubules:
MEISTER CYCLE (γ-glutamyl cycle)

Glutathione synthetase

GGT

Oxoprolinase
• Detoxification of Xenobiotics:
Conjugation reactions (transfers cysteinyl group)
Catalysed by Glutathione-S-transferase(GST)
R+GSH R-S-G (liver)
Other metabolic roles of cysteine
• Formation of Taurine:
(conjugation of Bile acids)
• Contributes to the formation of Coenzyme A:

• Coenzyme A is always written as CoA-SH when it is not

esterified.
CoA-SH+ Fatty acid-COOH Fatty Acyl-CoA +H20
 Homocysteine
Not coded by any codon,
Not found in proteins,
Produced in the metabolism
of methionine

Homocysteine

METHIONINE CYSTEINE

CYSTINE
 HOMOCYSTINURIAS

• Increased levels of homocystine in blood.

• Normal levels: 5-15μmol/L
• 50-100 times increased in Homocystinurias
• There is increased excretion of Hcy in urine

• High levels of Hcy in blood Cardiovascular risk

• Homocysteine interacts and interferes with the
collagen of the blood vessels  ENDOTHELIAL
DYSFUNCTION.

• Apart from these there are skeletal deformities and

lens dislocations

• Homocysteine (Hcy) metabolite:

Thioester Hcy-thiolactone, plays an important role in
atherothrombosis.
 HOMOCYSTINURIA-Types

TYPE III
TYPE IV
TYPE II

TYPE I
 CYSTINURIA
• Defect in the transport of amino acids:
Cysteine, Ornithine, Arginine, Lysine
(There is mutation in the amino acid transporter which
transports these amino acids in proximal renal tubules
and Enterocytes)

• Abnormal excretion of cysteine and to a

lesser extent other amino acids.

• This condition is also known as CYSTINE-

LYSINURIA
• Formation of cystine stones especially in acidic
pH of urine.

T/t:
 Plenty of fluids
 Alkalinize the urine to prevent the conversion of
cysteine to cystine
 Summary
• Methionine is ESSENTIAL amino acid. Major
role in transmethylation reactions & formation
of Cysteine.
• Both Methionine & Cysteine are Glucogenic
• SAM and its uses
• Special derivatives from Cysteine: Glutathione,
CoA, Taurine.
• Homocystinuria & Cystinuria
Thank you