Relative importance of the two major pathways for the conversion of cysteine to glucose in the perfused rat liver.

The effects of dietary treatments and substrate availability on the rate of gluconeogenesis from L-cysteine has been investigated in the perfused rat liver. At an optimal concentration (10 mM) of [U-14C]cysteine, after 40 minutes, 3.9% of the label appeared in glucose. This corresponded to 90% of the net glucose coming from cysteine. Cysteine was then shown to be converted to glucose at a physiological concentration of substrate (0.1 mM) as well as at the optimal concentration. After 40 minutes of perfusion with 0.1 mM [U-14C]cysteine as the substrate, livers of 72-hour starved rats incorporated 1.7% of the label into glucose, and livers of rats perfused without prior starvation incorporated 0.53% of the label into glucose. This suggested that cysteine was glucogenic at optimal and physiological concentrations of cysteine in both fed and starved rats. To determine which, if either, of the two suggested pathways for the conversion of cysteine to glucose was quantitatively more important, livers were perfused with [U-14C]cysteine alone or with [U-14C]cysteine plus cysteine sulfinic acid. The addition of cysteine sulfinate (10 mM) reduced the incorporation of 14C from cysteine into glucose from 3.9 to 2.7%. This suggested that one-third of the cysteine to glucose proceeded via the cysteine sulfinate-dependent pathway.