Methylglyoxal is a test for biological dysfunctions of homeostasis and endoecology, low cytosolic glucose level, and gluconeogenesis from fatty acids


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Abstract

If a lot of carbohydrates cannot be in vivo stored as glycogen, the synthesis of palmitic fatty acid (FA) from glucose and its adipocyte deposition as triglycerides are under way in phylogenesis. With impaired biological function of exotrophy (fasting, early postnatality, hibernation), the cells perform a reverse process - the synthesis of glucose from FA. Physiologically, the substrate of gluconeogenesis is acetyl-CoA that is converted by the malate → piruvate → glucose pathway in the glyoxalate cycle. Under the pathological conditions of hypoxia and energy deficiency, gluconeogenesis occurs without ATP consumption via the methylglyoxalate pathway (MGP) while using as a substrate of ketone bodies: butyric acid (butyrate) → β-hydroxybutyrate → acetoacetate → acetone → acetol → methylglyoxal (MG) → S-D-lactolglutathione → D-lactate → piruvate → D-lactate. Under physiological conditions, this pathway of gluconeogenesis does not work. The authors hold that gene expression and gluconeogenesis occur via the MGP when glucose levels are low in the cell cytosol (glycopenia) and FA cannot be oxidized in the mitochondria. Cytosol, intercellular medium, plasma show elevated levels of MG and D-lactate, to which it converts under the action of glyoxalases I and II. Glycopenia develops in fasting, diabetes mellitus, metabolic syndrome, renal failure, phenofibrate therapy, impaired function of exotrophy - excessive dietary intake of saturated and trans fatty acids. The chemical interaction of MG with amino acid residues of lysine and arginine leads to protein denaturation during carbonylation - glycosylation and impaired biological function of endoecology. The determination of plasma MG and D-lactate may be a test for glycopenia, compensatory activation of gluconeogenesis from FA or for the evaluation of endogenous intoxication.

References

  1. Титов В. Н. C-реактивный белок - вектор переноса жирных кислот к клеткам, которые непосредственно реализуют синдром системного воспалительного ответа. Клин. лаб. диагн. 2008; 6: 3-13.
  2. Лебкова Н. П. Современные представления о внутриклеточных механизмах обеспечения энергетического гомеостаза в норме и при патологии. Вестн. РАМН 2000; 9: 16- 22.
  3. Kosugi K., Scofield R. F., Chandramouli V. et al. Pathways of acetone's metabolism in the rat. J. Biol. Chem. 1986; 261: 3952-3957.
  4. Лейтес С. М., Лаптева Н. Н. Очерки по патофизиологии обмена веществ и эндокринной системы. М.: Изд-во "Медицина"; 1967.
  5. Титов В. Н., Пицин Д. Г. Влияние однократного введения этанола на синтез липидов и липопротеинов в печени крыс. Биохимия 1978; 43 (1): 83-88.
  6. Келдыш И. Н. Регуляция углеводного обмена. М.: Медицина; 1985. С. 271.
  7. Girard J. Metabolic adaptations to change of nutrition at birth. Biol. Neonat. 1990; 1 (1): 3-15.
  8. Wang W., Ballatori N. Endogenous glutathione conjugates occurrence and biological functions. Pharmacol. Rev. 1998; 50: 335-354.
  9. Akadi S., Ohmori S. Threonine is the best substrate for D-lactate formation in octopus rentacle. Amino Acids 2004; 26: 169-174.
  10. Ultsch G. R., Reese S. A., Stewart E. R. Physiology of hibernation in Rana pipiens: metabolic rate, critical oxygen tension, and the effect of hypoxia on several on plasma variables. J. Exp. Zool. A. Comp. Exp. Biol. 2004; 301: 169-176.
  11. Okamoto I., Kayano T., Hanaya T. et al. Up-regulation of an extracellular superoxidedismutase-like activity in hibernating hamsters subjected to oxidative stress in midto late arousal from torpor. Biochem. Physiol C. Toxicol. Pharmacol. 2006; 144: 47-56.
  12. John D. Annual lipid cycles in hibernation: integration of physiology and behavior. Annu. Rev. Nutr. 2005; 25: 468-497.
  13. Andrews M. T., Russeth K. P., Drewes L. R., Henry P. G. Adaptive mechanism regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009; 296: 383-393.
  14. Frerichs K. U., Dienel G. A., Cruz N. F. et al. Rates of glucose utilization in brain of active and hibernating ground squirrels. Am. J. Physiol. 1995; 268: 445-453.
  15. Kondrashov P. A., Koonin E. V., Morgunov I. G. et al. Evolution of glyoxylate cycle enzymes in Metazoa: evidence of multiple horizontal transfer events and pseudogene formation. Biol. Direct. 2006; 1: 31-42.
  16. Creilghton D. J., Hamilton D. S. Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations. Arch. Biochem. Biophys. 2001; 387: 10-18.
  17. Mannervik B. Molecular enzymology of the glyoxalase system. Drug. Metab. Drug. Interact. 2008; 23: 13-27.
  18. Голубев А. Г. Изнанка метаболизма. Биохимия 1996; 6 (1): 2018-2028.
  19. Thornalley P. J. The potential role of thiamine (vitamin B1) in diabetic complications. Curr. Diabet. Rev. 2005; 1: 287-298.
  20. Aronsson A. C., Marmstal E., Mannervik B. Glyoxalase I., a zinc metalloenzyme of mammals and yeast. Biochem. Biophys. Res. Commun. 1978; 81: 1235-1240.
  21. Casazza J. P., Felver M. E., Veech R. L. The metabolism of acetone in rat. J. Biol. Chem. 1984; 259: 231-236.
  22. Kalapos M. P. The tandem of free radicals and methylglyoxal. Chem. Biol. Interact. 2008; 171: 251-271.
  23. Chang W. C., Hsieh Y. Y., Cheng T. C. et al. Effect of methylglyoxal on mouse embryogenesis. Chang. Gung. Med. J. 2001; 24: 251-257.
  24. Fasanmade O. A., Odeniyi I. A., Ogbera A. O. Diabetic ketoacidosis: diagnosis and management. Afr. J. Med. Sci. 2008; 37: 99-105.
  25. Eledrisi M. S., Alshanti M. S., Shah M. F. et al. Overview of the diagnosis and management of diabetic ketoacidosis. Am. J. Med. Sci. 2006; 331: 243-251.
  26. Turk Z., Nemet I., Varga-Defteardarovic L., Car N. Elevated level of methylglyoxal during diabetic ketoacidosis and its recovery phase. Diabet. et Metab. 2006; 32: 176-180.
  27. Thorpe S. R., Lyons T. J., Baynes J. W. Glycation and glycoxidation in vascular disease. In: Keaney J. F. ed. Oxidative stress and vascular disease. Norwell: Kluwer Academic Publishers; 2000. 259-285.
  28. Singh R., Barden A., Von T., Belin L. Advanced glycation end-products: a review. Diabetologia 2002; 44: 129-146.
  29. Nemet I., Turk Z., Duvnjak L. et al. Humoral methylglyoxal level reflects glycemic fluctuation. Clin. Biochem. 2005; 38: 379-383.
  30. Reichard G. A., Skutches C. L., Hoeldke R. D., Owen O. E. Acetone metabolism in humans during diabetic ketoacidosis. Diabetes 1986; 35: 668-674.
  31. Phillips S. A., Thornalley P. J. The formation of methylglyoxal from triosephosphates. Investigation using a specific assay for methylglyoxal. Eur. J. Biochem. 1993; 212: 101-105.
  32. Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabet. Metab. Res. Rev. 1999; 15: 412-426.
  33. Александровский Я. А. Молекулярные механизмы взаимовлияния патологических процессов при совместном протекании сахарного диабета и рака. Биохимия. 2002; 67 (12): 1611-1631.
  34. Beisswenger B. G., Delucla E. M., Lapont N. et al. Ketosis leads to increased methylglyoxal production on the Atkins diet. Ann. N. Y. Acad. Sci. 2005; 1043: 201-210.
  35. Thornalley P. J. Clyoxalase I - structure, function and a critical role in the enxymatic defence against glycation. Biochem. Soc. Trans. 2003; 31: 1343-1348.
  36. Vantyghem M. C., Baiduck M., Zerimech F. Oxidative markers in diabetic ketoacidosis. J. Endocrinol. Invest. 2000; 23: 732- 736.
  37. Caprio S., Ray T. K., Boden G. et al. Improvement of metabolic control in diabetic patients during mebendazole administration: preliminary studies. Diabetologia 1984; 27: 52-55.
  38. Desai K. M., Wu L. Free radical generation by methylglyoxal in tissues. Drug. Metab. Drug. Interact. 2008; 23: 151-173.
  39. Kalapos M. P. Methylglyoxal in living organisms. Chemistry, biochemistry, toxicology and biological implications. Toxicol. Lett. 1999; 110: 145-175.
  40. Beisswenger P., Howell S. K., Nelson R. G. et al. Alpha-oxoaldehyde metabolism and diabetic complications. Biochem. Soc. Trans. 2003; 31: 1358-1363.
  41. Скулачев В. П. H2O2 - сенсоры легких и кровеносных сосудов и их роль в антиоксидантной защите организма. Биохимия 2001; 66 (10): 1425-1434.
  42. Бернштейн Л. М. Гормональный канцерогенез. СПб.: Наука, 2000.
  43. Dmitriev L. F., Dugin S. F. Aldehydes and disturbance of carbohydrate metabolism: some consequences and possible approaches to its normalization. Arch. Physiol. Biochem. 2007; 113: 87-95.
  44. Barski O. A., Tipparaju S. M., Bhatnagar A. The aldo-keto reductase superfamily and its role in drug metabolism and detoxification. Drug Metab. Rev. 2008; 40: 553-624.
  45. Thornalley P. J., Jahan I., Ng R. Suppression of the accumulation of triosephosphates and increased formation of methylglyoxal in human red blood cells during hyperglycaemia by thiamine in vitro. J. Biochem. (Tokyo) 2001; 129; 543-549.
  46. Miyata T., van Ypersele de Strihou C., Imasawa T. et al. Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient. Kidney Int. 2001; 60: 2351-2359.
  47. Miyata T., van Ypersele de Strihou C., Kurokawa K., Baynes J. W. Alterations in nonenzymatic biochemistry in uremia: origin and significance of "carbonyl stress" in long-term uremic complications. Kidney Int. 1999; 55: 389-399.
  48. Uribarri J., Cai W., Peppa M. et al. Circulating glycotoxins and dietary advanced glycation end producta: two links to inflammatory response, oxidative stress, and aging. J. Gerontol. A. Biol. Sci. Med. Sci. 2007; 62: 427-433.
  49. Migliore L., Barale R., Bosco E. et al. Genotoxicity of methylglyoxal: cytogenetic damage in human lymphocytes in vitro and in intestinal cells of mice. Carcinogenesis 1990; 11: 1503- 1507.
  50. Farah R., Shurtz-Swirski R., Lapin O. Intensification of oxidative stress and inflammation in type 2 diabetes despite antihyperglycemic treatment. Cardiovasc. Diabetol. 2008; 7: 20-28.
  51. Kondoh Y., Kawase M., Kawakami Y., Ohmori S. Concentrations of D-lactate and its related metabolic intermediates in liver, blood, and muscle of diabetic and starved rats. Res. Exp. Med. 1992; 192: 407-414.

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