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Inherited disorders in the conversion of methionine to homocysteine

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Journal of Inherited Metabolic Disease

Summary

During the last decade much important new information relating to the metabolic pathway from methionine to homocysteine has been gained. Interest has been stimulated by the discovery of two novel disorders, glycine N-methyltransferase deficiency and S-adenosylhomocysteine hydrolase deficiency. Another disorder in this pathway, methionine adenosyltransferase deficiency, has been increasingly detected, thanks to the expansion of newborn screening programmes by tandem mass spectrometry technology. These significant steps allow important insight into the pathogenesis of these three disorders, as well as into the mechanisms of damage to various organs (liver, brain, muscle) and point to the relevance of these disorders for crucial biological processes such as methylation, transsulfuration or carcinogenesis in mammals, the pathogenesis of numerous pathological conditions, in particular those associated with hyperhomocysteinaemia, the action and possible toxicity of some drugs or consequences of nutritional variations. This review summarizes current knowledge of three inherited disorders in this metabolic pathway and draws attention to their much broader significance for human health and understanding of important biological processes.

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Abbreviations

AdoHcy:

S-adenosylhomocysteine

AdoMet:

S-adenosylmethionine

CBS:

cystathionine beta-synthase

CK:

creatine kinase

GNMT:

glycine N-methyltransferase

HCC:

hepatocellular carcinoma

MAT:

methionine adenosyltransferase

PEMT:

phosphatidylethanolamine N-methyltransferase

SAHH:

S-adenosylhomocysteine hydrolase

tHcy:

total homocysteine

TMS:

tandem mass spectrometry

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Acknowledgements

This work was supported by grant 108-1081870-1885 of the Ministry of Science, Education and Sport of Republic of Croatia. Brian Fowler is gratefully acknowledged for his critical and supporting review of the manuscript and S. Harvey Mudd for his great teaching and motivating contribution to the author’s work in this field. The author is grateful to all his colleagues for their continuous support.

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Authors and Affiliations

  1. Department of Pediatrics, University Hospital Center and School of Medicine, Zagreb, Croatia

    Ivo Barić

  2. Department of Pediatrics, University Hospital Center, Kišpatićeva 12, Rebro, 10000, Zagreb, Croatia

    Ivo Barić

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  1. Ivo Barić
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Correspondence to Ivo Barić.

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Communicating editor: Brian Fowler

Competing interests: None declared

References to electronic databases: OMIM catalogue: http://www.ncbi.nlm.nih.gov/omim/; Enzyme Commission numbers: http://www.chem.qmul.ac.uk/iubmb/enzyme/. MAT I/III deficiency: OMIM 250850; Methionine adenosyltransferase (MAT) EC 2.5.1.6. GNMTdeficiency: OMIM 606664. Glycine N-methyltransferase (GNMT): EC 2.1.1.20. AdoHcy hydrolase deficiency: OMIM 180960. S-Adenosylhomocysteine hydrolase: EC 3.3.1.1.

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Barić, I. Inherited disorders in the conversion of methionine to homocysteine. J Inherit Metab Dis 32, 459–471 (2009). https://doi.org/10.1007/s10545-009-1146-4

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