Hyperhomocysteinemia - Which body tissues contribute to plasma homocysteine entry and removal?

J.J.G.C. van den Borne, F.A. Wilson, A.G. Calder, N. O'Kennedy, G. Holtrop, W.D. Rees, G.E. Lobley

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Abstract

Impaired transfer of methyl groups, as occurs during folate and choline deficiency, leads to plasma hyperhomocysteinemia and increases the risk for cardiovascular disease. Tissue sources of plasma homocysteine in vivo have not been quantified and it has not been elucidated whether hyperhomocysteinemia is due increased entry into or decreased removal from blood. These issues were addressed in rats offered diets with either adequate or inadequate folate and choline for 5 wk. A new model was used for measuring tissue metabolism based on isotopomer analysis after continuous intravenous infusion with [U-13C]methionine (massþ5) plus [1-13C]homocysteine (massþ1). Folate and choline deficiency led to hyperhomocysteinemia. Decreased clearance from plasma did not contribute to the high plasma homocysteine as most tissues increased the fraction of intracellular homocysteine derived by importation from plasma by 33–106%. Methylation rates were highest in liver and pancreas, but the liver did not play a dominant role as the source of plasma homocysteine. Much of the homocysteine generated within the liver was (re)methylated and the enrichment of hepatic homocysteine derived from demethylation was less than that observed in plasma. In pancreas, the enrichment of massþ4 homocysteine was highest and exceeded that of plasma. Enrichment of massþ1 methionine was highest in the heart, indicating substantial import and methylation of plasma [1-13C]homocysteine. In conclusion, plasma hyperhomocysteinemia results from increased entry rather than decreased removal. The pancreas, rather than liver, is a major exporter of homocysteine, whereas much intracellular homo- cysteine is imported from plasma in tissues such as heart, which may affect cardiovascular function
Original languageEnglish
Pages (from-to)S15 (P25)-S16
JournalEuropean Journal of Clinical Nutrition
Volume63
Issue numberSuppl. 3
DOIs
Publication statusPublished - 2009

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    van den Borne, J. J. G. C., Wilson, F. A., Calder, A. G., O'Kennedy, N., Holtrop, G., Rees, W. D., & Lobley, G. E. (2009). Hyperhomocysteinemia - Which body tissues contribute to plasma homocysteine entry and removal? European Journal of Clinical Nutrition, 63(Suppl. 3), S15 (P25)-S16. https://doi.org/10.1038/ejcn.2009.72