Methylenetetrahydrofolate reductase: A common human polymorphism and its biochemical implications

被引：39

作者：

Matthews, RG ^{[1
]}

机构：

[1] Univ Michigan, Biophys Res Div, Ann Arbor, MI 48109 USA

来源：

CHEMICAL RECORD | 2002年 / 2卷 / 01期

关键词：

flavoprotein; homocysteine; methionine;

D O I：

10.1002/tcr.10006

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Methlenctetrahydrofolate (CH2-H(4)folate) is required for the conversion of homocysteine to methionine and of dUMP to dTMP in support of DNA synthesis, and also serves as a major source of one carbon unit for purine biosynthesis. This review presents biochemical studies of a human polymorphism in methylenetetrahydrofolate reductase,which catalyzes the reaction shown below. The mutation decreases the flux of CH2-H(4)folate into CH3-H(4)folate, and is associated with both beneficial and deleterious effects that can be traced to the molecular effect of the substitution of alanine 222 by valine. (C) 2002 The Japan Chemical Journal Forum and John Wiley Sons, Inc.

引用

页码：4 / 12

页数：9

共 36 条

[21]

MATTHEWS RG, 1984, J BIOL CHEM, V259, P1647

[22] C-13 NMR ANALYSIS OF INTERCOMPARTMENTAL FLOW OF ONE-CARBON UNITS INTO CHOLINE AND PURINES IN SACCHAROMYCES-CEREVISIAE [J].

PASTERNACK, LB ;

LAUDE, DA ;

APPLING, DR .

BIOCHEMISTRY, 1994, 33 (01) :74-82

[23] STRUCTURES OF THYMIDYLATE SYNTHASE WITH A C-TERMINAL DELETION - ROLE OF THE C-TERMINUS IN ALIGNMENT OF 2'-DEOXYURIDINE 5'-MONOPHOSPHATE AND 5,10-METHYLENETETRAHYDROFOLATE [J].

PERRY, KM ;

CARRERAS, CW ;

CHANG, LC ;

SANTI, DV ;

STROUD, RM .

BIOCHEMISTRY, 1993, 32 (28) :7116-7125

[24] Homocysteine and cardiovascular disease [J].

Refsum, H ;

Ueland, PM ;

Nygård, O ;

Vollset, SE .

ANNUAL REVIEW OF MEDICINE, 1998, 49 :31-62

[25] REFINED CRYSTAL-STRUCTURE OF CD, ZN METALLOTHIONEIN AT 2.0 A RESOLUTION [J].

ROBBINS, AH ;

MCREE, DE ;

WILLIAMSON, M ;

COLLETT, SA ;

XUONG, NH ;

FUREY, WF ;

WANG, BC ;

STOUT, CD .

JOURNAL OF MOLECULAR BIOLOGY, 1991, 221 (04) :1269-1293

[26] Purification and properties of NADH-dependent 5,10-methylenetetrahydrofolate reductase (MetF) from Escherichia coli [J].

Sheppard, CA ;

Trimmer, EE ;

Matthews, RG .

JOURNAL OF BACTERIOLOGY, 1999, 181 (03) :718-725

[27]

STEEGERSTHEUNISSEN RPM, 1991, NEW ENGL J MED, V324, P199

[28]

SUMNER J, 1986, J BIOL CHEM, V261, P7697

[29] STEREOCHEMISTRY AND MECHANISM OF HYDROGEN TRANSFER BETWEEN NADPH AND METHYLENETETRAHYDROFOLATE IN THE REACTION CATALYZED BY METHYLENETETRAHYDROFOLATE REDUCTASE FROM PIG-LIVER [J].

SUMNER, JS ;

MATTHEWS, RG .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (18) :6949-6956

[30] Methylenetetrahydrofolate reductase from Escherichia coli:: Elucidation of the kinetic mechanism by steady-state and rapid-reaction studies [J].

Trimmer, EE ;

Ballou, DP ;

Matthews, RG .

BIOCHEMISTRY, 2001, 40 (21) :6205-6215

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