The essentiality of sulfur is closely related to nitrogen metabolism: a clue to hyperhomocysteinaemia

Abstract

N and S metabolisms are closely interwoven throughout both the plant and animal kingdoms. The essentiality of S relates to its participation in the structure of S-containing amino acids (SAA), to its inclusion in many sulfonated molecules, and to a myriad of metabolic and catalytic reactions of vital importance. Methionine (Met) is the indispensable SAA supplied by food proteins and its plasma homeostasis is achieved via a number of highly efficient regulatory mechanisms. In all conditions characterised by a negative body protein balance such as in dietary restriction or cytokine-induced hypercatabolic losses, N and S endogenous pools manifest parallel tissue depletion rates. Adaptive conservation of N and S body stores is reached by a functional restraint of the trans-sulfuration cascade, through the depression of cystathionine ␤-synthase activity. As a result, upstream accumulation of homocysteine favours its re-methylation conversion to Met which helps maintain metabolic pathways of survival value. In addition to the measurement of vitamin indices, that of plasma transthyretin, a sensitive marker of protein nutritional status, is proposed to identify the fluctuations of the total body N component accountable for the alterations of homocysteine concentrations in body fluids.

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

“…The concept was clearly counterintuitive in that it was unexpected that high Hcy plasma values might result from low intake of its precursor Met molecule. Despite the low SAA intake of our vegetarian patients [27], plasma Met concentrations disclosed noticeable stability allowing to maintain the synthesis and functioning of myriads of Metdependent molecular, structural and metabolic compounds described in detail elsewhere [30,44]. These clinical investigations have received strong support from recent mouse [45] and rat [46] experiments submitted to Met-restricted regimens.…”

“…We have postulated the existence of an independent sensor mechanism set in motion by TBS pool shrinkage and reduced bioavailability of Met -its main building block -working as an inhibitory feedback loop of C S activity [30]. Such Met-bodystat, likely to be centrallymediated, and aiming at maintaining unaltered Met disposal in conditions of decreased dietary provision implies the fulfillment of high metabolic priorities of survival value [30,44].…”

“…The vegetable kingdom is unable to assimilate S 8 and requires as prior step its natural or bacterial oxidation to SO 4 2-derivatives before launching the synthesis of SAA molecules along narrowly regulated metabolic pathways [30,44]. Distinct anabolic processes are identified in mammalian tissues which lack the enzymatic equipment required to organize sulfate oxyanions but possess the capacity of direct S 8 conversion into H 2 S. S 8 is poorly soluble in tap waters [68] may be taken up and transported to mammalian tissues loosely fastened to serumalbumin (SA) [69].…”

Why should plasma transthyretin become a routine screening tool in elderly persons?

“…This last proportion does not optimally fulfills human body requirements, implying that strict vegans are permanently at risk of incuring N-and S-deficiencies. Moreover, any acute or chronic disorder causes cytokine-induced tissue proteolysis documented by urinary leakage of tightly correlated amounts of N-and S-catabolites (27,28), attesting that total body N (TBN) and total body S (TBS) pools are exhausted concomitantly.…”

“…In contrast to all other IAAs, the preservation of normal methioninemia implies high metabolic priority best explained by the roles played by Met in the synthesis of S-containing molecules of survival importance and in the production of a myriad of S-compounds with significant molecular, structural and functional properties (28). Hyperhomocysteinemia thus appears as the dark side of efforts provided by N-and Sdepleted individuals to maintain Met homeostasis.…”