Hyperhomocysteinemia is a Biomarker of Sulfur-Deficiency in HumanMorbidities

摘要

Methionine (Met) is crucially involved in the synthesis of S-compounds endowed with molecular, structuraland functional properties of survival value. Dietary Met may undergo transmethylation processes to release homocysteine(Hcy) which may either be regenerated to Met following remethylation (RM) pathways or catabolized along the transsulfuration(TS) cascade. The activity of enzymes governing RM and TS pathways is depending on pyridoxine, folate andcobalamin bioavailability. Dietary restriction in any of these watersoluble B-vitamins may lead to hyperhomocysteinemia(HHcy) causing a panoply of cardiovascular disorders. Taken together, the vitamin triad only affords partial account ofHcy variance, prompting the search for additional causal factor(s). Body composition studies demonstrate that nitrogen(N) and sulfur (S) maintain tightly correlated concentrations in tissues of both healthy subjects and diseased patients. Anymorbid condition characterized by insufficient N intake or assimilation, as seen in protein malnutrition or intestinalmalabsorption, reduces body S accretion rates. Excessive urinary N-losses, as reported in acute or chronic inflammatorydisorders, entail proportionate obligatory S-losses. As a result, lean body mass (LBM) undergoes downsizing and concomitantdepletion of N and S body stores which depresses the activity of cystathionine--synthase, thereby promotingupstream accumulation of Hcy and overstimulation of RM processes. HHcy thus appears as the dark side of efforts developedby S-deprived patients to safeguard Met homeostasis. Irrespective of vitamin-B status, Hcy values are negativelycorrelated with LBM shrinkage well identified by the serial measurement of plasma transthyretin (TTR). The Sdeprivationtheory fulfills the gap and allows full causal coverage of the metabolic anomaly, hence providing togetherwith vitamin-deficiencies an unifying overview of the main nutritional determinants implicated in HHcy epidemiology.