Effects of protein, methionine, or chloride on acid-base balance and on cysteine catabolism

Abstract

Metabolism of cysteine to sulfate results in production of H+, whereas metabolism of cysteine to taurine does not. Rats were fed a basal low-protein diet or a diet with excess protein, methionine, or chloride for 2-3 wk, and effects of these treatments on acid-base homeostasis and on cysteine metabolism were determined. Hepatocytes from rats fed diets with excess methionine, but not from rats fed diets with excess protein or chloride, catabolized a high proportion of cysteine to taurine (32% vs. 4-7% for other groups), and intact rats fed excess methionine excreted more sulfur as taurine (51% of total sulfur vs. 1-6% for other groups). The formation of taurine vs. sulfate as the end product of cysteine catabolism provides a metabolic compensation that minimizes the acid load in rats fed excess sulfur amino acids. However, increased production of taurine vs. sulfate is not a general adaptive response to acidogenic diets.

Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase

“…In the wild-type animal, hepatic metabolism of cysteine is responsible for the majority of taurine synthesis (3,4,13). In the CDO Ϫ/Ϫ mouse, tissue and plasma taurine concentrations were reduced to less than 10% of wild-type levels (30).…”

Regulation of cysteine dioxygenase and γ-glutamylcysteine synthetase is associated with hepatic cysteine level

“…In addition, the absence of any effect of diet on the polysome profile observed for CDO mRNA [19] and the inability of cycloheximide or emitine, which block protein synthesis, to prevent the accumulation of CDO in response to supplemental sulfur amino acids in primary cultures of rat hepatocytes [31] indicate that CDO is regulated at the level of degradation rather than synthesis.…”

“…A large physiological effect of changes in CDO activity on the capacity of an animal to catabolize cysteine to taurine and sulfate/pyruvate has been demonstrated by differences in rates of product formation by isolated rat hepatocytes from rats adapted to diets that contained various levels of protein or sulfur amino acid and by different tissue and urinary taurine and sulfate levels in intact rats adapted to these same diets [12,13,15]. Similarly, an effect of hepatic GCS activity on the capacity (at a given cysteine level) of the animal to synthesize glutathione has been demonstrated by differences in the rates of glutathione synthesis by isolated rat hepatocytes from rats adapted to diets that contained various levels of protein or sulfur amino acid [13,18,19].…”

Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate

“…Mammalian cysteine dioxygenase (CDO, encoded by the Cdo1 gene) catalyzes the conversion of cysteine to cysteinesulfinate and, thus, initiates a pathway of cysteine catabolism in which its sulfur is oxidized at the first step (Stipanuk 2004; Stipanuk and Ueki 2011; Stipanuk et al 2009). CDO concentration and activity are robustly regulated in response to the sulfur amino acid content of the diet (Bella and Stipanuk 1995; Dominy et al 2006, 2008; Stipanuk et al 2004) and act to maintain cellular cysteine levels within a homeostatic range. One important consequence of CDO’s role in maintenance of low cellular cysteine levels is the prevention of excess metabolism of cysteine to hydrogen sulfide (H 2 S, which exists as an equilibrium mixture of HS − and H 2 S at physiological pH) by the alternative cysteine desulfhydration pathways.…”