The phosphogluconate pathway and synthesis of 5-phosphoribosyl-1-pyrophosphate in human fibroblasts.
The phosphogluconate pathway (pentose phosphate cycle) of normal fibroblasts was stimulated 20-fold by methylene blue and inhibited to 14% of the baseline rate by 6-aminonicotinamide. In fibroblasts deficient in glucose-6-phosphate dehydrogenase activity (an average of 1.5% of normal mean), the pentose phosphate cycle was unaffected by either methylene blue or 6-aminonicotinamide. In normal cells, neither the intracellular concentration nor the rate of generation of 5-phosphoribosyl-1-pyrophosphate was altered by the marked and opposite changes in the rate of the phosphogluconate pathway caused by methylene blue and 6-aminonicotinamide. Intracellular ribose 5-phosphate concentration was increase by methylene blue (an average increase of 83%) but not significantly altered by 6-aminonicotinamide. In fibroblasts deficient in glucose-6-phosphate dehydrogenase activity, the 5-phosphoribosyl-1-pyrophosphate concentration and rate of generation were higher rather than lower in comparison to normal cells under all conditions studied. The data suggest a predominant role for the nonoxidative branch of the phosphogluconate pathway in supplying ribose 5-phosphate for nucleotide biosynthesis. Pentose phosphate supply cannot be considered an essential function of the oxidative branch in fibroblasts.
D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D005942:Gluconates / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010428:Pentosephosphates / Q000096:biosynthesis* / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis*; D012267:Ribosemonophosphates / Q000378:metabolism; D012867:Skin; D013403:Sugar Phosphates / Q000378:metabolism
D005942:Gluconates; D010428:Pentosephosphates; D012267:Ribosemonophosphates; D013403:Sugar Phosphates; D010754:Phosphoribosyl Pyrophosphate; C008884:6-phosphogluconic acid