Homocystinuria due to cystathionine β-synthase (CBS) deficiency

doi:10.1017/CBO9780511545054.028

26 - Homocystinuria due to cystathionine β-synthase (CBS) deficiency

Published online by Cambridge University Press: 31 July 2009

Raffaella de Franchis ,

Ennio del Giudice and

Generoso Andria

Edited by

E. Steve Roach and

Van S. Miller

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Raffaella de Franchis: Affiliation:
Federico II University, Department of Pediatrics, Via S. Pansini 5, 80131 Naples, Italy
Ennio del Giudice: Affiliation:
Federico II University, Department of Pediatrics, Via S. Pansini 5, 80131 Naples, Italy
Generoso Andria: Affiliation:
Federico II University, Department of Pediatrics, Via S Pansini 5, 80131 Naples, Italy
E. Steve Roach: Affiliation:
Wake Forest University, North Carolina
Van S. Miller: Affiliation:
University of Texas Southwestern Medical Center, Dallas

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Summary

Introduction

Homocystinuria due to cystathionine β-synthase (CBS) deficiency (MIM # 236200) is the most common inborn error of sulfur amino acid metabolism. It is inherited as an autosomal recessive trait. The frequency of the disease has been estimated between 1 in 200 000 and 1 in 335 000 (Mudd et al., 1989), though several lines of evidence indicate that this frequency might be higher (Mudd et al., 1995).

Sulfur-containing amino acids, homocysteine, methionine and cysteine are linked by the remethylation cycle and the trans-sulfuration pathway (Fig. 26.1). CBS (shape l-serine hydrolyase; EC 4.2.1.22) catalyzes the condensation of homocysteine with serine to form the thioether cystathionine, a reaction requiring pyridoxal-phosphate as cofactor (Fig. 26.1, enzyme 2). Cystathionine is cleaved to cysteine and α-ketobutyrate by another pyridoxal-phosphate-dependent enzyme, γ-cystathionase (enzyme 3). The trans-sulfuration pathway ends converting sulfite to sulfate and is catalyzed by sulfite oxidase (enzyme 4), requiring a molybdenum cofactor. Conversion of methionine into homocysteine proceeds via methionine adenosyltransferase (enzyme 1) yielding S-adenosylmethionine, a methyl-group donor used in several transmethylation reactions, and S-adenosylhomocystein e, which is cleaved to adenosine and homocysteine. About 50% of homocysteine, not entering the trans-sulfuration pathway, is recycled into methionine. This step involves methyl transfer either from 5-methyl-tetrahydrofolate (THF), catalyzed by cobalamin-requiring 5-methyl THF-homocystei ne methyltransferase (methionine synthase, MS, enzyme 5), or from betaine, catalyzed by betaine-homocysteine methyltransferase (enzyme 6).

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Type: Chapter
Information: Neurocutaneous Disorders , pp. 206 - 213

DOI: https://doi.org/10.1017/CBO9780511545054.028 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2004

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