The Oxidative Stress of Hyperhomocysteinemia Results from ReducedBioavailability of Sulfur-Containing Reductants

摘要

Vegetarian subjects consuming subnormal amounts of methionine (Met) are characterized by subclinical proteinmalnutrition causing reduction in size of their lean body mass (LBM) best identified by the serial measurement ofplasma transthyretin (TTR). As a result, the transsulfuration pathway is depressed at cystathionine-β-synthase (CβS) leveltriggering 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) valuesdownstream to CβS causing in turn declining generation of hydrogen sulfide (H2S) from enzymatic sources. The biogenesisof H2S via non-enzymatic reduction is further inhibited in areas where earth’s crust is depleted in elemental sulfur (S8)and sulfate oxyanions. Combination of subclinical malnutrition and S8-deficiency thus maximizes the defective productionof Cys, GSH and H2S reductants, explaining persistence of unabated oxidative burden. The clinical entity increasesthe risk of developing cardiovascular diseases (CVD) and stroke in underprivileged plant-eating populations regardless ofFramingham criteria and vitamin-B status. Although unrecognized up to now, the nutritional disorder is one of the commonestworldwide, reaching top prevalence in populated regions of Southeastern Asia. Increased risk of hyperhomocysteinemiaand oxidative stress may also affect individuals suffering from intestinal malabsorption or westernized communitieshaving adopted vegan dietary lifestyles.