Skip to main content
SpringerLink
Log in

Glucose-6-phosphate: A key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia

  • Treatment and complications in GSD type Ib
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The glycogen storage disorders (GSD)-I,-III,-VI and VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for atherosclerosis. The atherogenicity of triglycerides has remained controversial, while increased plasma cholesterol levels are generally accepted as a significant risk factor for coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where triglycerides are atherogenic and those which are not significantly related to early onset of atherosclerosis but may cause other disorders such as pancreatitis. Among the disorders of carbohydrate metabolism patients with diabetes mellitus frequently have enhanced plasma triglycerides associated with a higher risk for coronary heart disease, while patients with certain types of glycogen storage disease have high triglyceride levels but do not seem to have an enhanced risk for atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of glucose metabolism including GSD-I (glucose-6-phosphatase deficiency), favism (glucose-6-phosphate dehydrogenase deficiency), and diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that glucose-6-phosphate (Glc-6-P) is a central molecule in cellular glucose metabolism which critically influences pentose phosphate cycle activity and, via NADPH2-generation, regulates glutathione peroxidase activity for radical detoxification and also cholesterol and triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of membrane lipids may protect against the development of atherosclerosis. In GSD-I, the accumulation of Glc-6-P leads to enhanced radical detoxification and thereby increases the generation of “reducing”-equivalents. In contrast in both glucose-6-phosphate dehydrogenase deficiency and diabetes mellitus there is an impaired activity of the glutathione-peroxidase system and the NADPH2-generation pentose phosphate cycle which might predispose these patients for membrane damage thus leading to haemolysis, platelet activation and atherosclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

GSD:

glycogen storage disease

Glc-6-P:

glucose-6-phosphate

HDL:

high density lipoproteins

LDL:

low density lipoproteins

VLDL:

very low density lipoproteins

PDGF:

platelet derived growth factor

References

  1. Alaupovic P, Fernandes J (1985) The serum apolipoprotein profile of patients with glucose-6-phosphatase-deficiency. Pediatr Res 19:380–384

    PubMed  Google Scholar 

  2. Austin MA (1988) Epidemiologic associations between hypertriglyceridemia and coronary heart disease. Semin Thromb Hemost 14: 137–142

    Google Scholar 

  3. Block LH, Knorr W, Vogt E, Lochner R, Vetter W, Groscurth P, Quiao BY, Pometta D, James R, Regenass M, Pletscher A (1988) Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism. Proc Natl Acad Sci USA 85:885–889

    PubMed  Google Scholar 

  4. Bradley WA, Hwang SC, Karlin JB, Lin AHY, Prasad SC, Gotte AM Jr, Gianturco SH (1984) Low density lipoprotein receptor binding determinants switch from apolipoprotein E to apolipoprotein B during conversion of hypertriglyceridemic very low density lipoprotein to low density lipoprotein. J Biol Chem 259:14728–14735

    PubMed  Google Scholar 

  5. Brown SA, Via DP, Gotto AM Jr, Bradley WA, Gianturco SH (1986) Apolipoprotein E mediated binding of hypertriglyceridemic very low density lipoproteins to isolated low density lipoprotein receptors detected by ligand blotting. Biochem Biophys Res Commun 139:333–340

    PubMed  Google Scholar 

  6. Collier A, Wilson R, Bradley H, Thomson JA, Small M (1990) Free radical activity in type 2 diabetes. Diabetic Med 7:27–30

    PubMed  Google Scholar 

  7. Dessi S, Laconi E, Batetta B, Pani P (1983) Effect of 3-MC on cholesterolemia and hepatic G-6-PD. Res Commun Chem Pathol Pharmacol 41: 333–336

    PubMed  Google Scholar 

  8. Dessi S, Batetta B, Laconi E, Ennas C, Pani P (1984) Hepatic cholesterol in lead nitrate induced liver hyperplasia. Chem Biol Interact 48:271–279

    PubMed  Google Scholar 

  9. Dessi S, Chiodino C, Batetta B, Laconi E, Ennas C, Pani P (1986) Hepatic glucose-6-phosphate dehydrogenase, cholesterologenesis, and serum lipoproteins in liver regeneration after partial hepatectomy. Exp Mol Pathol 44:169–176

    PubMed  Google Scholar 

  10. Esterbauer H, Benedetti A, Lang J, Fulceri F, Fauler G, Comporti M (1986) Studies on the mechanism of formation of 4-hydroxynonenal during microsomal lipid peroxidation. Biochem Biophys Acta 876:154–166

    PubMed  Google Scholar 

  11. Fernandes J, Pikaar NA (1969) Hyperlipidemia in children with liver glycogen disease. Am J Clin Nutr 22:617–627

    PubMed  Google Scholar 

  12. Forget PP, Fernandes J, Haverkamp-Begemann P (1974) Triglyceride clearing in glycogen storage disease. Pediatr Res 8:114–119

    PubMed  Google Scholar 

  13. Foster DW (1989) Diabetes mellitus. In: Scriver CR, Beaudet A, Sly W, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 375–397

    Google Scholar 

  14. Garnier M, Attali JR, Valensi P, Delatour-Hanss E, Gaudey F, Koutsouris D (1990) Erythrocyte deformability in diabetes and erythrocyte membrane lipid composition. Metabolism 39:794–798

    PubMed  Google Scholar 

  15. Gianturco SH, Eskin SG, Navarro LT, Lahart CJ, Smith LC, Gotto jr AM (1980) Abnormal effects of hypertriacylglycerolemic very low density lipoproteins on 3-hydroxy-3-methylglutaryl-CoA reductase activity and viability of cultured bovine aortic endothelial cells. Biochem Biophys Acta 618:143:152

    Google Scholar 

  16. Gianturco SH, Bradley WA, Gotto jr AM, Morrisett JD, Peavy DL (1982) Hypertriglyceridemic very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages. J Clin Invest 70:168–178

    PubMed  Google Scholar 

  17. Gianturco SH, Lin AHY, Hwang SL, Young J, Brown SA, Via DP, Bradley WA (1988) Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins. J Clin Invest 82:1633–1643

    PubMed  Google Scholar 

  18. Gillery P, Monboisse JC, Maquart FX, Borel JP (1989) Does oxygen free radical increased formation explain long term complications of diabetes mellitus? Med Hypotheses 29:47–50

    PubMed  Google Scholar 

  19. Hayakawa M, Kuzuya F (1990) Free radicals and diabetes mellitus. Nippon Ronen Igakkai Zasshi 27:149–54

    PubMed  Google Scholar 

  20. Hers HG, Hoof F van, Barsy T de (1989) Glycogen storage disease. In: Scriver CR, Beaudet A, Sly W, Valle D (eds) The metabolic basis of inherited disease. 6th edn. McGraw-Hill, New York, pp 425–452

    Google Scholar 

  21. Hülsman WC, Eijkenboom WHM, Koster JF, Fernandes J (1970) Glucose-6-phosphatase-deficiency and hyperlipidemia. Clin Chem Acta 36:775–778

    Google Scholar 

  22. Kelley DS, Kletzien RF (1984) Ethanol modulation of the hormonal and nutritional regulation of glucose-6-phosphate dehydrogenase activity in primary cultures of rat hepatocytes. Biochem J 217:543–549

    PubMed  Google Scholar 

  23. Levy E, Thibault L, Roy CC, Letarte J, Lambert M, Seidman EG (1990) Mechanisms of hypercholesterolemia in glycogen storage disease type I: defective metabolism of low density lipoproteins in cultured skin fibroblasts. Eur J Clin Invest 20: 253–260

    PubMed  Google Scholar 

  24. Long WK, Wilson SW, Frenkel EP (1967) Associations between red cell glucose-6-phosphate dehydrogenase variants and vascular diseases. Am J Hum Genet 19:35–39

    PubMed  Google Scholar 

  25. Luzzatto L, Mehta A (1989) Glucose-6-phosphate dehydrogenase deficiency. In: Scriver CR, Beaudet A, Sly W, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2237–2266

    Google Scholar 

  26. Mahley RW, Rall SC Jr (1989) Type III hyperlipoproteinemia (dysbetalipoproteinemia). The role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In: Scriver CR, Beaudet A, Sly W, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 1195–1213

    Google Scholar 

  27. Muntoni S (1989) On behalf of the ATS-Sardegna research group. Serum lipoprotein levels in G-6-PD deficient Sardinians (abstract). Xth International Symposium on drugs affecting lipid metabolism, Houston, Texas, Nov 8–11. 1989. Abstract Book, p 108

  28. Muntoni S, Pintus F, Mascia P, Pintus P, Ganga E, Menotti A (1989) Lipidi plasmitici nella condizione di carenza di glucosio-6-fosfato deidrogenasi. Giorn Arterioscl 14:123–129

    Google Scholar 

  29. Quinn MT, Parthasarathy S, Steinberg D (1985) Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effect of modified forms of low density lipoprotein. Proc Natl Acad Sci USA 82:5949–5953

    PubMed  Google Scholar 

  30. Rao KN (1986) Regulatory aspects of cholesterol metabolism in cells with different degrees of replication. Toxicol Pathology 14:430–437

    Google Scholar 

  31. Srivastava SK, Ansari NH, Liu S, Izban A, Das B, Szabo G, Bhatnagar A (1989) The effect of oxidants on biomembranes and cellular metabolism. Mol Cell Biochem 91:149–157

    PubMed  Google Scholar 

  32. Steinberg D, Parthasarthy S, Carew TE, Khoo JC, Witzum JL (1989) Beyond cholesterol. Modification of low density lipoprotein that increases its atherogenecity. N Engl J Med 320: 915–924

    PubMed  Google Scholar 

  33. Welt SI, Jackson EH, Kirkman HN, Parker JC (1979) The effects of certain drugs on the hexose monophosphate shunt of human red cells. Ann NY Acad Sci 179:625–636

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität, Albert-Schweitzer-Strasse 33, W-4400, Münster, Federal Republic of Germany

    G. Schmitz & H. Hohage

  2. Klinik und Poliklinik für Pädiatrie, Westfälische Wilhelms-Universität, Albert-Schweitzer-Strasse 33, W-4400, Münster, Federal Republic of Germany

    K. Ullrich

Authors
  1. G. Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Hohage
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Ullrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmitz, G., Hohage, H. & Ullrich, K. Glucose-6-phosphate: A key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia. Eur J Pediatr 152 (Suppl 1), 77–84 (1993). https://doi.org/10.1007/BF02072094

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02072094

Key words

Search

Navigation