Introduction to Human Nutrition

The Vitamins 173

administration of methotrexate to inhibit tumor
growth, and folate (normally as 5-formyl-tetrahydro-
folate, leucovorin) to replete tissues and avoid folate
defi ciency; this is known as leucovorin rescue.

Methionine synthetase and
the methyl-folate trap
In addition to its role in the synthesis of proteins,
methionine, as the S-adenosyl derivative, acts as a
methyl donor in a wide variety of biosynthetic reac-
tions. As shown in Figure 8.16, the resultant homo-
cysteine may be either metabolized to yield cysteine
or remethylated to yield methionine.
Two enzymes catalyze the methylation of homo-
cysteine to methionine:

● Methionine synthetase is a vitamin B 12 -dependent

enzyme, for which the methyl donor is

methyl-tetrahydrofolate.

● Homocysteine methyltransferase utilizes betaine

(an intermediate in the catabolism of choline) as

the methyl donor, and is not vitamin B 12

dependent.

Both enzymes are found in most tissues, but only the

vitamin B 12 -dependent methionine synthetase is

found in the central nervous system.

The reduction of methylene-tetrahydrofolate to

methyl-tetrahydrofolate is irreversible, and the major

source of folate for tissues is methyl-tetrahydrofolate.

The only metabolic role of methyl-tetrahydrofolate is

the methylation of homocysteine to methionine, and

CH 3

S

CH 2

CH 2

HC NH 3 +

COO–

S-Adenosylmethionine

Methionine

ATP

PPi + Pi

Methionine adenosyltransferase

S-Adenosylhomocysteine

Adenosine

SH

CH 2

CH 2

HC NH 3 +

COO–

Methyl THF Homocysteine

Tetrahydrofolate

Methionine synthetase

Acceptor

Methylated product

Methyltransferases

Cystathionine

Cysteine

Serine

α-Ketobutyrate + NH 4 +

H 2 O

Cystathionine b -synthetase

H 2 O

g -Cystathionase

Homocysteine

Figure 8.16 Methionine metabolism. Methionine synthetase (EC 2.1.1.13), methionine adenosyltransferase (EC 2.5.1.6), cystathionine synthetase
(EC 4.2.1.22), cystathionase (EC 4.4.1.1).