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.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BRIN M., YONEMOTO R. H. Stimulation of the glucose oxidative pathway in human erythrocytes by methylene blue. J Biol Chem. 1958 Jan;230(1):307–317. [PubMed] [Google Scholar]
- BRUNNEMANN A., COPER H., NEUBERT D. BIOSYNTHESE UND WIRKUNG DES 6-AMINONICOTINAMIDE-ADENINDINUCLEOTIDS (6-ANAD) Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1964 Feb 13;246:437–451. [PubMed] [Google Scholar]
- Brand K., Arese P., Rivera M. Bedeutung und Regulation des Pentosephosphat-Weges in menschilichen Erythrozyten, I. Hoppe Seylers Z Physiol Chem. 1970 Apr;351(4):501–508. [PubMed] [Google Scholar]
- Del Boca J., Flatt J. P. Fatty acid synthesis from glucose and acetate and the control of lipogenesis in adipose tissue. Eur J Biochem. 1969 Nov;11(1):127–134. doi: 10.1111/j.1432-1033.1969.tb00749.x. [DOI] [PubMed] [Google Scholar]
- Greenbaum A. L., Gumaa K. A., McLean P. The distribution of hepatic metabolites and the control of the pathways of carbohydrate metabolism in animals of different dietary and hormonal status. Arch Biochem Biophys. 1971 Apr;143(2):617–663. doi: 10.1016/0003-9861(71)90247-5. [DOI] [PubMed] [Google Scholar]
- Gumaa K. A., McLean P. The pentose phosphate pathway of glucose metabolism. Enzyme profiles and transient and steady-state content of intermediates of alternative pathways of glucose metabolism in Krebs ascites cells. Biochem J. 1969 Dec;115(5):1009–1029. doi: 10.1042/bj1151009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herken H., Lange K., Kolbe H. Brain disorders induced by pharmacological blockade of the pentose phosphate pathway. Biochem Biophys Res Commun. 1969 Jul 7;36(1):93–100. doi: 10.1016/0006-291x(69)90654-8. [DOI] [PubMed] [Google Scholar]
- Kather H., Rivera M., Brand K. Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Effect of the amount of glucose uptake on the rates of the pentose phosphate cycle and of fatty acid synthesis. Biochem J. 1972 Aug;128(5):1089–1096. doi: 10.1042/bj1281089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz J., Landau B. R., Bartsch G. E. The pentose cycle, triose phosphate isomerization, and lipogenesis in rat adipose tissue. J Biol Chem. 1966 Feb 10;241(3):727–740. [PubMed] [Google Scholar]
- Katz J., Wals P. A. Effect of phenazine methosulfate on lipogenesis. J Biol Chem. 1970 May 25;245(10):2546–2548. [PubMed] [Google Scholar]
- Katz J., Wals P. A. Effects of phenazine methosulfate on glucose metabolism in rat adipose tissue. Arch Biochem Biophys. 1971 Dec;147(2):405–418. doi: 10.1016/0003-9861(71)90396-1. [DOI] [PubMed] [Google Scholar]
- Köhler E., Barrach H. -J., Neubert D. Inhibition of NADP dependent oxidoreductases by the 6-aminonicotinamide analogue of NADP. FEBS Lett. 1970 Feb 16;6(3):225–228. doi: 10.1016/0014-5793(70)80063-1. [DOI] [PubMed] [Google Scholar]
- Lange K., Kolbe H., Keller K., Herken H. Der Kohlenhydratstoffwechsel des Gehirns nach Blockade des Pentose-Phosphat-Weges durch 6-Aminoicotinsäureamid. Hoppe Seylers Z Physiol Chem. 1970 Oct;351(10):1241–1252. [PubMed] [Google Scholar]
- Lange K., Proft E. R. Inhibition of the 6-phosphogluconate dehydrogenase in the rat kidney by 6-aminonicotinamide. Naunyn Schmiedebergs Arch Pharmakol. 1970;267(2):177–180. doi: 10.1007/BF00999399. [DOI] [PubMed] [Google Scholar]
- Roigas H., Zoellner E., Jacobasch G., Schultze M., Rapoport S. Regulierende Faktoren der Methylenblaukatalyse in erythrocyten. Eur J Biochem. 1970 Jan;12(1):24–30. doi: 10.1111/j.1432-1033.1970.tb00816.x. [DOI] [PubMed] [Google Scholar]
- Saggerson E. D., Greenbaum A. L. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Biochem J. 1970 Sep;119(2):193–219. doi: 10.1042/bj1190193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Bruchhausen F., Herken H. Wirkung des 6-Aminonicotinsäureamids auf die Insulinabhängige Glucoseaufnahme in das epidiymale Fettgewebe. Naunyn Schmiedebergs Arch Pharmakol Exp Pathol. 1966;254(4):388–400. [PubMed] [Google Scholar]