Kwame Nkrumah University of

Science & Technology, Kumasi, Ghana

CATABOLISM OF SULFUR
CONTAINING AMINO ACIDS

Dr Max Efui Annani-Akollor

Dept of Molecular Medicine

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 Lecture Outline
• Metabolism of Methionine
Homocysteinuria
Cystathionuria
• Metabolism of Cysteine
• One carbon Metabolism
Biotin
Tetrahydrofolate

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 LECTURE OBJECTIVES

• Identify key intermediates and end products in the catabolism of sulfur

containing amino acids.
• Know some clinical outcomes of errors in catabolism of methionine and
cysteine
• Explain how Biotin and Tetrahydrofolate are involved in one carbon
metabolism

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 METABOLISM OF METHIONINE
•The major metabolic fate of
methionine are:
•Its conversion to S-adenosyl
methionine, the principal methyl
group donor in biosynthetic
reactions
•Its conversion through the trans-
sulfuration pathway leads to
synthesis of cystathionine,
cysteine and other biosynthetic
intermediates
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•These two metabolic fates are
however related since methionine
may be converted sequentially to:
–S-adenosyl methionine
–S-adenosyl homocysteine
–Homocyteine
•Homocysteine is then converted
irreversibly to cystathionine by a PLP
requiring cystathionine-β synthase
•Cystathionine is then converted to
cysteine and α-ketobutyric acid by a
PLP requiring γ-lyase
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• α-ketobutyric acid is then oxidatively
decarboxylated to propionyl CoA
• Cysteine suppresses the synthesis of
cystathionine β synthase
• It is also an allosteric inhibitor of
cystathionine γ lyase
• The net effect of these reactions is the
transfer of the sulfhydryl group of
homocysteine to the carbon chain of serine

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 Homocystinuria
• This condition is characterized by the deficiency of cystathionine β
synthase
• It is associated with the accumulation of homocysteine in the blood
and their excretion in the urine
• There is also the accumulation of methionine in the blood of
affected persons

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• The accumulated homocysteine reacts with lysyl semialdehydes and thus
interferes with cross-linking of collagen
• The accumulated homocysteine may be converted to homocysteinethiolactone
• Homocysteine thiolactone modified LDL leads to their aggregation and
atheroma formation.
• Affected individuals present with severe mental retardation and connective
tissue defects such as:
– Deformation of the spine
– Dimineralisation of bone
– Dislocation of joints
– Aortic aneurysms
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• They may also present with:
• Bilateral dislocation of the lenses
• Fair complexion with blue eyes
• Hepatomegaly

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• Management of this condition entails the
provision of extra cysteine in the diet of
affected individuals
• Restrict the intake of methionine containing
diets but feed with betaine or its precursor
choline
• Some subjects may respond favourably to
pyridoxine therapy

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 Cystathionuria
• This is a rare metabolic defect characterized by
the deficiency of cystathionine γ lyase
• It may also result from an imbalance between
the synthesis and degradation of cystathionine
• The condition may also be associated with
either the reduced affinity of the γ lyase or the
deficiency of PLP
• Affected subjects accumulate cystathionine in
the blood and excrete high levels in their urine

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Most affected subjects are asymptomatic
• Some subjects may present with the following;
• Small liver
• Pale liver
• Fibrotic liver

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 Metabolism of Cysteine
• Cysteine has several metabolic fates
• The pathway of degradation is determined by
the needs of the cell:
• The major route for cysteine catabolism is a
three step pathway leading to pyruvate.

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• It may be converted to hypotaurine and
taurine

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• Taurine appears to play a role in brain
development
• Taurine may form a conjugate with bile acids
to enhance the clearance of cholesterol by the
liver
• Taurine participates in the clearance of
xenobiotics and toxins
• It is probably involved in the regulation of
intracellular [calcium]
• It may be involved in osmoregulation

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• Cysteine may be metabolised to sulfite and
pyruvate

• Sulfite may be converted to sulfate under the

catalysis of mitochondrial sulfite oxidase
• Sulfate, subsequently metabolised to 3’-
phosphoadenosine 5’-phosphosulfate (PAPS),
the source of sulfate groups in biological
systems
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• Deficiency of sulfite oxidase results in the
excretion of large amounts of thiosulfate and
sulfite
• Affected subjects present with neurological
abnormalities at birth which deteriorates
progressively and results in early death

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• Cysteine may be metabolised to thiocysteine
and thiosulfate which may be converted to
thiocyanate

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 One Carbon Metabolism
• One carbon transfers involve one of three
cofactors: biotin, tetrahydrofolate or S-
adenosyl methionine
• These cofactors are used for the transfer of one
carbon groups in different oxidation states

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• The various oxidation states of carbon
encountered in metabolism are:
• Carbon dioxide
• Formyl (-CHO)
• Formimino (-CHNH-)
• Methenyl (-CH=)
• Methylene (-CH2-)
• Methyl (-CH3)

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 Biotin
• This is a human vitamin obtained from the diet
• It is also synthesized by the intestinal flora
• It is involved in the carboxylation reactions
• Biotin may be sequestered by avidin which is
found in uncooked egg white

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 Tetrahydrofolate
• It is otherwise known as tetrahydropteroyl
glutamate
• It consists of a substituted pteridine, para
amino benzoate and glutamate
• It is a human vitamin obtained from the diet
• It may be synthesized by the intestinal flora

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• Tetrahydrofolate is a highly versatile carrier of
activated one carbon units
• The one carbon units may be bonded to its N5,
N10 nitrogen atom or both (N5, N10)
• The one carbon atoms carried by
tetrahydrofolate are interconvertible
• They serve as donors of one carbon units in a
variety of biosynthetic reactions

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• The major source of one carbon units for
tetrahydrofolate is the carbon removed in the
conversion of serine to glycine

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