Hyperhomocysteinemia is a Biomarker of Sulfur-Deficiency in Human Morbidities~!2009-10-03~!2009-11-18~!2009-12-22~!

Abstract

Methionine (Met) is crucially involved in the synthesis of S-compounds endowed with molecular, structural and 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 and cobalamin 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 of Hcy 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. Any morbid condition characterized by insufficient N intake or assimilation, as seen in protein malnutrition or intestinal malabsorption, reduces body S accretion rates. Excessive urinary N-losses, as reported in acute or chronic inflammatory disorders, entail proportionate obligatory S-losses. As a result, lean body mass (LBM) undergoes downsizing and concomitant depletion of N and S body stores which depresses the activity of cystathionine--synthase, thereby promoting upstream accumulation of Hcy and overstimulation of RM processes. HHcy thus appears as the dark side of efforts developed by S-deprived patients to safeguard Met homeostasis. Irrespective of vitamin-B status, Hcy values are negatively correlated with LBM shrinkage well identified by the serial measurement of plasma transthyretin (TTR). The Sdeprivation theory fulfills the gap and allows full causal coverage of the metabolic anomaly, hence providing together with vitamin-deficiencies an unifying overview of the main nutritional determinants implicated in HHcy epidemiology.

Cystathionine β-synthase and cystathionine γ-lyase double gene transfer ameliorate homocysteine-mediated mesangial inflammation through hydrogen sulfide generation

“…None of these pathways are related to protein malnutrition and/or of cytokineinduced stressful disorders. A fifth mechanism of HHcy development has been reported in patients suffering from protein malnutrition and/or intestinal malabsorption characterized by insufficient N intake or assimilation, which also reduces body S accretion rates (19). This is an adaptive mechanism depressing the activity of CBS and allows accumulation of Hcy in biological fluids.…”

“…Accumulated Hcy during this process in turn through remethylation maintain methionine homeostasis. HHcy in this regard considered as (19,49). However, if HHcy is due to pathways involving 1-4 reasons, as stated above, it could be both as a consequence and/or causal factor depending on the source.…”

Nutritional essentiality of sulfur in health and disease

“…Egg white is a notable exception, constituting one of the richest sources of S (S:N ratio, 1:10). The data provided by N and S balance studies indicate that the fate of dietary S is not distinguishable from that of N, implying that the body's capacity to enter into anabolic drive and to generate net tissue protein gain is the requisite determinant of S accretion rate …”

Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging

“…Plasma transthyretin is a sensitive marker of protein energy malnutrition (109). Decreased plasma transthyretin is associated with elevated plasma homocysteine in protein energy malnutrition, which is a biomarker for sulfur deficiency, as shown in Figure 8 (107).…”