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.

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.

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.

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.

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.

Methionine SAM

S-adenosylhomocysteineHomocysteine

ATP 2Pi + Pi

Methionine adenosyltransferase

Acceptor

Methylated product

Methyl transferaseCH3

Adenosylhomocysteinase

H2OAdenosine

THF

N5-Methyl THF

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

Textbook of Biochemistry-U Satyanarayana

Textbook of Biochemistry-DM Vasudevan