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Editors: Ralph Carmel, Donald W Jacobsen
510pp. Price £110 ISBN 0-521-65319-3 (h/b)
Cambridge: Cambridge University Press .
‘The study of obscure subjects has a way of generating ultimately important intellectual ideas and practical advances’—thus begins this 500-page tome on homocysteine. Many of us justify some of our more recherché projects with such arguments, and for homocysteine the dream is coming true. This intriguing molecule was discovered over 70 years ago and is important in the methionine cycle which allows methyl group transfers that are essential for life, and because of its participation in redox reactions by dint of its reactive sulphydryl group. In medicine, homocysteine first came to prominence because of inborn errors of metabolism leading to homocystinuria—a disorder characterized by dislocation of the lens, a marfanoid habitus, mental retardation and thromboembolic disease. This latter manifestation is thought to be due to endothelial damage and has led to a much wider interest in the possibility that raised homocysteine levels in the general population may be a marker for excess cardiovascular risk.
It is now clear that there is a relationship between increased homocysteine and certain types of cardiovascular risk, and dietary, environmental and genetic causes (common polymorphic variation) have been implicated as a mechanism of raised homocysteine. What is less clear is why a high homocysteine level should be bad news. Theories abound, from increased oxidant stress to enhanced methyldonation; many are rehearsed in detail in this book, but none is yet conclusive nor do we know whether intervention to lower homocysteine will produce benefit. Elevated homocysteine may also be the mechanism by which folate deficiency enhances risk of neural tube defect, and through a common genetic variant in the 5, 10 methylenetetrahydrofolate reductase gene, about 11% of the UK population need extra folate to keep homocysteine levels down.
This book is impressive in its scope and comes at a time when many have heard of homocysteine but few really understand the molecule. It deals with the chemistry, biology, medical aspects and potential for intervention. It has helpful tips on how to measure homocysteine, how variable measurements are, how to intervene and how to manipulate the pathway experimentally. This is hardly the stuff of core curriculum, but for the increasing number of people, from epidemiologists to vascular biologists and embryologists, who are looking at homocysteine as part of their research this could provide an invaluable handbook. Why do I think this would be useful? The answer is simple—the large number of people who have walked into my office whilst this book has been lying on my desk and said ‘Can I take a look at that when you have finished?’.