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Factors Affecting the Rate of Gluconeogenesis from L-Cysteine in the Perfused Rat Liver^{1, 2,}

Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis, California

It has been shown that the net rate of gluconeogenesis from cysteine was only 10% the rate observed from pyruvate. This suggested that the rate limiting step in gluconeogenesis from cysteine was between cysteine and pyruvate. Evidence is presented showing that the cysteine-sulfinate pathway does not play a regulating role in the conversion of cysteine to glucose. Thus, liver cysteine desulfhydrase (CDS) activity and hydrogen sulfide production were evaluated for their potential effects. Liver CDS activity was increased by a 3 day starvation, by feeding a 90% casein diet or a 4% cysteine + 86% casein diet. In all cases the activity of the enzyme was in excess of that required to account for the rate of conversion of cysteine to glucose observed, thus the potential activity of this enzyme was not a rate limiting factor. The possible effect of H₂S, an end product of the CDS reaction, on gluconeogenesis from cysteine was evaluated. The addition of NaHS abolished the glucogenic response observed from cysteine, but had very little effect on gluconeogenesis from lactate, suggesting that accumulated H₂S may inhibit CDS, making CDS rate limiting in the conversion of cysteine to pyruvate.

KEY WORDS: • cysteine • gluconeogenesis • cysteine desulfhydrase • hydrogen sulfide

¹ Supported by Grant USPHS AM-04732 and Procter and Ganible Fellowship.

² A preliminary report was presented at the 58th Annual Meeting of the Federation of American Societies of Experimental Biology, 13–18 April, 1975, Atlantic City, N.J. Federation Proc. 34, (Abstr.)

Manuscript received 28 August 1975.

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