Archives of biochemistry and biophysics

The reactions of the phosphorylated pathway of L-serine biosynthesis: thermodynamic relationships in rat liver in vivo.

PMID 3004357


The effect of the induction of the enzymes of the phosphorylated pathway of L-serine biosynthesis on the thermodynamic relationships among the reactions has been determined in rat liver in vivo. The mass action ratios of the reactions involved were calculated from the concentrations of appropriate metabolites in freeze-clamped liver from animals fed normal and low-protein diets for 2 weeks. These ratios were compared with the equilibrium constants of the same reactions previously determined under physiological conditions and the results previously obtained in the rabbit. The thermodynamic relationships in the pathway were different between the normal rat and rabbit as might have been expected, because of the significantly lower activities of the L-serine biosynthetic enzymes in the former animal. Although the delta G for the overall pathway is nearly identical in the rat and rabbit (-5.8 versus -5.5 kcal/mol, respectively), the distribution of delta G among the reactions is different. The disequilibrium in the pathway in rat liver is nearly equally divided between the L-phosphoserine phosphatase (EC step and the other two reactions [D-3-phosphoglycerate dehydrogenase (EC and L-phosphoserine aminotransferase (EC], whereas in rabbit the phosphatase reaction accounts for nearly the entire delta G. Feeding the rat a low protein diet, however, induced the activity of D-3-phosphoglycerate dehydrogenase 12-fold, that of L-phosphoserine aminotransferase 20-fold, and that of L-phosphoserine phosphatase 2-fold. With the induction of the pathway, L-phosphoserine appeared in the tissue, there was a more than 3-fold rise in L-serine in the liver, and the pattern of delta G in the rat liver approached that in the rabbit.