title: Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Control of pentose phosphate-cycle activity by cellular requirement for reduced nicotinamide adenine dinucleotide phosphate.
abstract: By using inhibitors and stimulators of different metabolic pathways the interdependence of the pentose phosphate cycle and lipogenesis in isolated fat-cells was studied. Rotenone, which is known to inhibit electron transport in the respiratory chain, blocked glucose breakdown at the site of pyruvate dehydrogenase. Consequently, because of the lack of acetyl-CoA, fatty acid synthesis was almost abolished. A concomitant decrease in pentose phosphate-cycle activity was observed. Phenazine methosulphate stimulated pentose phosphate-cycle activity about five- to ten-fold without a considerable effect on fatty acid synthesis. The influence of rotenone on both the pentose phosphate cycle and lipogenesis could be overcome by addition of phenazine methosulphate, indicating that rotenone has no direct effect on these pathways. The decreased rate of the pentose phosphate cycle in the presence of rotenone therefore has to be considered as a consequence of decreased fatty acid synthesis. The rate of glucose catabolism via the pentose phosphate cycle in adipocytes appears to be determined by the requirement of NADPH for lipogenesis. Treatment of cells with 6-aminonicotinamide caused an accumulation of 6-phosphogluconate, indicating an inhibition of 6-phosphogluconate dehydrogenase. The rate of glucose metabolism via the pentose phosphate cycle as well as the rate of fatty acid synthesis, however, was not affected by 6-aminonicotinamide treatment and could still be stimulated by addition of insulin. Since even in cells from starved animals, in which the pentose phosphate-cycle activity is extremely low, no accumulation of 6-phosphogluconate was observed, it is concluded that the control of this pathway is achieved by the rate of regeneration of NADP at the site of glucose 6-phosphate dehydrogenase.
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks; D002245:Carbon Dioxide; D002247:Carbon Isotopes; D005227:Fatty Acids / Q000096:biosynthesis; D005942:Gluconates; D005947:Glucose / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase; D066298:In Vitro Techniques; D007658:Ketone Oxidoreductases; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D009249:NADP / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D010428:Pentosephosphates / Q000378:metabolism*; D010619:Phenazines; D011773:Pyruvates; D051381:Rats; D012402:Rotenone / Q000494:pharmacology
chemical_list: D002247:Carbon Isotopes; D005227:Fatty Acids; D005942:Gluconates; D008055:Lipids; D010428:Pentosephosphates; D010619:Phenazines; D011773:Pyruvates; D012402:Rotenone; D002245:Carbon Dioxide; D009536:Niacinamide; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D007658:Ketone Oxidoreductases; D005947:Glucose