methionine metabolism
TRANSCRIPT
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The sulfur – containing amino acids are
methionine, cysteine & cystine.
Methionine is glucogenic & essential amino acid.
It serves as a precursor for the synthesis of
cysteine & cystine which are non-essential.
Cysteine & cystine are interconvertible.
Cystine is found exclusively in protein.
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Methionine & cysteine, besides present in
proteins, are involved in many important
metabolic reactions.
Methionine is also required for the initiation
of protein biosynthesis.
The sulfur - containing amino acids are almost
an exclusive dietary source of sulfur to the
body.
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Methionine (or sulfur amino acids)
metabolism may be divided into three parts.
1. Utilization of methionine for
transmethylation reactions.
2. Conversion of methionine to cysteine &
cystine.
3. Degradation of cysteine & its conversion to
specialized products.
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The transfer of methyl group (-CH3) from
active methionine to an acceptor is known
as transmethylation.
Methionine has to be activated to S-
adenosylmethionine (SAM) or active
methionine to donate the methyl group.
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The synthesis of SAM occurs by the transfer of
adenosyl group from ATP to sulfur atom of
methionine.
This reaction is catalysed by methionine S-
adenosyltransferase (MAT).
There are 3 isoenzymes for MAT, out of which 1
& 3 are of hepatic origin.
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Methionine SAM
S-adenosylhomocysteineHomocysteine
ATP 2Pi + Pi
Methionine adenosyltransferase
Acceptor
Methylated product
Methyl transferaseCH3
Adenosylhomocysteinase
H2OAdenosine
THF
N5-Methyl THF
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SAM is the main source of methyl groups in
body.
The activation of methionine is unique as the
sulfur becomes a sulfonium atom (SAM is a
sulfonium compound) by the addition of a
3rd Carbon.
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This reaction is also unusual since all the
three phosphates of ATP are eliminated as
pyrophosphates (PPi) & inorganic
phosphates (Pi).
Three high energy phosphates (3ATP) are
consumed in the formation of SAM.
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Methyl group acceptor Methylated product
Guanidinoacetate Creatine
Norepinephrine Epinephrine
Epinephrine Metanephrine
Ethanolamine Choline
Nicotinamide N-Methylnicotinamide
Acetyl serotonin Melatonin
Phosphatidylethanolamine Phosphatidylcholine
Serine Choline
Carnosine Anserine
t-RNA bases Methylated t-RNA bases
Lysine Methyl lysine
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SAM is highly reactive due to the presence of
a positive charge.
The enzymes involved in the transfer of
methyl group are collectively known as
methyltransferases.
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SAM transfers the methyl group to an
acceptor & gets itself converted to S-
adenosylhomocysteine.
Homocysteine:
S-Adenosylhomocysteine (SAH) is hydrolysed
(adenosyl group is removed) to homocysteine
& adenosine.
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Methionine synthesis:
Homocysteine can be remethylated to
methionine by N5-methyl tetrahydrofolate.
This methyl group is donated from one-
carbon pool, with the help of vitamin B12.
In this manner, methionine can be
regenerated for reuse.
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Homocysteine degradation:
Homocysteine condenses with serine to form
cystathionine.
This is catalysed by PLP dependent
cystathionine-β-synthase.
Absence of this enzyme leads to
homocystinuria.
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Transmethylation is of great biological
significance since many compounds become
functionally active only after methylation.
Protein (amino acid residues) methylation
helps to control protein turnover.
Methylation protects the proteins from
immediate degradation.
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In plants, S-adenosylmethionine is the
precursor for the synthesis of a plant
hormone, ethylene, which regulates plant
growth & development & is involved in the
ripening of fruits.
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Causes of hypermethioninemia:
1. Impaired utilization.
2. Excessive remethylation of homocysteine.
3. Secondary to hepatic dysfunction.
Oasthouse syndrome is due to malabsorption
of methionine.
Such children excrete methionine, aromatic &
branched chain amino acids in urine.
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Textbook of Biochemistry-U Satyanarayana
Textbook of Biochemistry-DM Vasudevan
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