A kinetic study of the isozymes determined by the three human phosphoglucomutase loci PGM1, PGM2, and PGM3.

Abstract

The isozyme products (PGM1, PGM2 and PGM3) of the three human phosphoglucomutase genes (PGM1, PGM2 and PGM3) were separated and compared as phosphoglucomutases, phosphoribomutases and glucose 1,6‐bisphosphatases.The Km values for glucose 1‐phosphate (Glc‐1‐P) were estimated at various glucose 1,6‐bisphosphate concentrations. When the glucose 1,6‐bisphosphate concentration was less than 10 μM, PGM1 was seen to be much more effective at catalysing the phosphoglucomutase reaction than either PGM2 or PGM3. The effect of the coenzyme (glucose 1,6‐bisphosphate) concentration was studied and was found to affect the Km for Glc‐1‐P of PGM2. As the glucose 1,6‐bisphosphate concentration was increased the Km decreased; this effect was particularly noticeable over the concentration range 100 μM to 400 μM where a small alteration in glucose 1,6‐bisphosphate concentration produced a marked fall in the value of the Km for Glc‐1‐P of PGM2. The concentration of glucose 1,6‐bisphosphate in a range of human tissues was estimated and was found to be within the range 10 μM to 600 μM in most tissues.PGM2 was found to be more effective at catalysing the phosphoribomutase reaction than PGM1. The Km for ribose 1‐phosphate for neither the PGM1, nor the PGM2 isoenzymes was affected by the concentration of glucose 1,6‐bisphosphate. The possibility of glucose 1,6‐bisphosphate acting on PGM2 and thereby directing whether it functions as a phosphoribomutase or a phosphoglucomutase has been discussed. Ribose 1‐phosphate inhibited the phosphoglucomutase activity of the products of all three loci. The ribose 1‐phosphate appeared, from Dixon plots, to be competing with glucose 1‐phosphate.The effect of 2,3‐bisphosphoglycerate on the phosphoglucomutase activity of the PGM1 and PGM2 isozymes was examined; this compound was found to inhibit by competing with glucose 1,6‐bisphosphate in both cases.The ability of the isoenzymes of all three genes to catalyse a glucose 1,6‐bisphosphatase reaction has been reported. The Km values for glucose 1,6‐bisphosphate for this reaction were estimated as being of the order of 1000 μM.