A Kinetic Study of the Isozymes Determined by the Three Human Phosphoglucomutase Loci PGM₁, PGM₂ and PGM₃

The isozyme products (PGM 1 , PGM 2 and PGM 3 ) of the three human phosphoglucomutase genes ( PGM 1 , PGM 2 and PGM 3 ) were separated and compared as phosphoglucomutases, phosphoribomutases and glucose 1,6‐bisphosphatases. The K m 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, PGM 1 was seen to be much more effective at catalysing the phosphoglucomutase reaction than either PGM 2 or PGM 3 . The effect of the coenzyme (glucose 1,6‐bisphosphate) concentration was studied and was found to affect the K m for Glc‐1‐ P of PGM 2 . As the glucose 1,6‐bisphosphate concentration was increased the K m 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 K m for Glc‐1‐ P of PGM 2 . 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. PGM 2 was found to be more effective at catalysing the phosphoribomutase reaction than PGM 1 . The K m for ribose 1‐phosphate for neither the PGM 1 , nor the PGM 2 isoenzymes was affected by the concentration of glucose 1,6‐bisphosphate. The possibility of glucose 1,6‐bisphosphate acting on PGM 2 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 PGM 1 and PGM 2 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 K m values for glucose 1,6‐bisphosphate for this reaction were estimated as being of the order of 1000 μM.