The Oxidative Stress of Hyperhomocysteinemia Results from Reduced Bioavailability of Sulfur-Containing Reductants

Abstract

Vegetarian subjects consuming subnormal amounts of methionine (Met) are characterized by subclinical protein malnutrition causing reduction in size of their lean body mass (LBM) best identified by the serial measurement of plasma transthyretin (TTR). As a result, the transsulfuration pathway is depressed at cystathionine--synthase (C S) level triggering the upstream sequestration of homocysteine (Hcy) in biological fluids and promoting its conversion to Met. Maintenance of beneficial Met homeostasis is counterpoised by the drop of cysteine (Cys) and glutathione (GSH) values downstream to C S causing in turn declining generation of hydrogen sulfide (H 2 S) from enzymatic sources. The biogenesis of H 2 S via non-enzymatic reduction is further inhibited in areas where earth's crust is depleted in elemental sulfur (S 8 ) and sulfate oxyanions. Combination of subclinical malnutrition and S 8 -deficiency thus maximizes the defective production of Cys, GSH and H 2 S reductants, explaining persistence of unabated oxidative burden. The clinical entity increases the risk of developing cardiovascular diseases (CVD) and stroke in underprivileged plant-eating populations regardless of Framingham criteria and vitamin-B status. Although unrecognized up to now, the nutritional disorder is one of the commonest worldwide, reaching top prevalence in populated regions of Southeastern Asia. Increased risk of hyperhomocysteinemia and oxidative stress may also affect individuals suffering from intestinal malabsorption or westernized communities having adopted vegan dietary lifestyles.

Growth rate and metabolic parameters in young turkeys fed diets with different inclusion levels of methionine

“…Both the highest and lowest dietary Met levels exerted similar effects on many parameters (concentrations of vitamin C and LOOH, activity of CAT and GPx, FRAP values). Ingenbleek (2011) demonstrated that dietary Met deficiency induced oxidative stress in vegetarian subjects consuming deficient amounts of Met. In another experiment (Castellano et al, 2015), a decrease in blood FRAP values was noted in piglets fed Met-deficient diets.…”

Nutritional essentiality of sulfur in health and disease

“…Decreased enzymatic and nonenzymatic production 39,165,166,293 Increased production cancelled out by tissue overconsumption 79 Abbreviations: CRP, C-reactive protein; LBM, lean body mass; S, sulfur; SAA, S-containing amino acids; SO4 2-, sulfate. a LBM shrinking may be the result of either dysmaturation of body protein tissues as an effect of protracted dietary SAA deprivation or of cytokine-induced depletion of body stores.…”

Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression

“…Homocysteine metabolism involves two pathways, that is, trans-sulfuration pathway and re-methylation pathway [1]. Homocysteine metabolism involves two pathways, that is, trans-sulfuration pathway and re-methylation pathway [1].…”

“…Homocysteine is a nonproteogenic sulfurated amino acid derived from ingested methionine found in cheese, eggs, fish, meat, and poultry. Homocysteine metabolism involves two pathways, that is, trans-sulfuration pathway and re-methylation pathway [1]. Homocysteine is metabolized and detoxified by trans-sulfuration to cysteine, via enzymes (cystathionine-b-synthase and cystathionine-c-lyase) dependent on vitamin B 6 as a cofactor [2,3].…”