The dysfunction of anaplerotic pathway of energy metabolism from amino acids to succinate in the elderly
https://doi.org/10.18705/1607-419X-2011--1 -
Abstract
Mitochondrial dysfunction is shown to develop progressively in people older than 55 years due to anaplerotic pathway disturbances accompanied by methylmalonic acidemia. Hyperhomocysteinemia and methylmalonic acidemia are accompanied by decrease of valine and leucine, and methionine elevation. Systemic manifestations of mitochondrial dysfunction depend on the methylmalonyl-CoA-mutase activity, and the adenosylcobalamine, as a cofactor and the others proteins defi ned, as transporters of the cofactor. This metabolic state was defi ned as an anaplerotic dysfunction in the paper. The discussed metabolic dysfunction in elderly people differs from the one in adults with Vitamin B12 functional defi ciency. The elevation of branched chain amino acids is usually observed in methylmalonic acidemia. We conclude that anaplerotic dysfunction should be considered a possible factor of initiation and progression of arterial hypertension.
About the Authors
A. A. Zhloba
Pavlov St Petersburg State Medical University, Biochemistry Department;
Almazov Federal Heart, Blood and Endocrinology Centre, St Petersburg
Russian Federation
Russian Federation
E. G. Mayevskaya
Pavlov St Petersburg State Medical University, Biochemistry Department,
St Petersburg
Russian Federation
Russian Federation
References
1. Постнов Ю.В., Орлов С.Н., Будников Е.Ю. и др. Нарушение преобразования энергии в митохондриях клеток с уменьшением синтеза АТФ как причина стационарного повышения уровня системного артериального давления // Кардиология. - 2008. - Т. 48, № 8. -С. 49-59.
2.
3. Буйкин С.В., Голубенко М.В., Пузырев В.П. Участие «митохондриальных генов» в формировании гипертрофии левого желудочка при артериальной гипертонии // Мол. биол. - 2010. - Т. 44, № 1. -С. 28-32.
4.
5. Owen O.E., Kalhan S.C., Hanson R.W. The key role of anaplerosis and cataplerosis for citric acid cycle function // J. Biol. Chem. - 2002. -Vol. 277, № 34. - P. 30409-30412.
6.
7. Frenkel E.P. Abnormal fatty acid metabolism in peripheral nerves of patients with pernicious anemia // J. Clin. Invest. - 1973. - Vol. 52, № 5. - P. 1237-1245.
8.
9. Kasumov T., Cendrowski A.V., David F., Jobbins K.A., Anderson V.E., Brunengraber H. Mass isotopomer study of anaplerosis from propionate in the perfused rat heart // Arch. Biochem. Biophys. - 2007. -Vol. 463, № 1. - P. 110-117.
10.
11. Ostergaard E., Hansen F.J., Sorensen N. et al. Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations // Brain. - 2007. - Vol. 130, Pt. 3. - P. 853-861.
12.
13. Lamers Y., Williamson J., Gilbert L.R., Stacpoole P.W., Gregory J.F. 3rd. Glycine turnover and decarboxylation rate quantifi ed in healthy men and women using primed, constant infusions of [1,2-(13)C2]glycine and [(2)H3] leucine // J. Nutr. - 2007. - Vol. 137, № 12. - P. 2647-2652.
14.
15. Babidge P.J., Babidge W.J. Determination of methylmalonic acid by high-performance liquid chromatography // Anal. Biochem. - 1994. -Vol. 216, № 2. - P. 424-426.
16.
17. Gratzfeld-Huesgen A. Sensitive and reliable amino acid analysis in protein hydrolysaty using the HP 1100C series HPLC // Agielent technical note. - 1998-1999. URL: <http://ftp.neurop.ruhr-uni-bochum.de/pub/>HPLC/OPA-Methode.pdf
18.
19. Zhloba A.A., Blashko E.L. Liquid chromatographic determination of total homocysteine in blood plasma with photometric detection // J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. - 2004. - Vol. 800, № 1-2. - P. 275-280.
20.
21. Tиц Н.У. Клиническая оценка лабораторных тестов. - М.: Медицина, 1986. - С. 41-57.
22.
23. Gitlitz P.H., Sunderman F.W., Hohnadel D.C. Ion-exchange chromatography of amino acids in sweat collected from healthy subjects during sauna bathing // Clin. Chem. - 1974. - Vol. 20, № 10. -P. 1305-1312.
24.
25. Polge A., Bancel E., Bellex H. et al. Plasma amino acid concentrations in elderly patients with protein energy malnutrition // Age Ageing. -1997. - Vol. 26, № 6. - P. 457-462.
26.
27. Светлицкая С.Г. Мегалобластические анемии // Медицина (Минск). - 2004. - № 1. - C. 30-32.
28.
29. Heil S.G., Lievers K.J.A., Boers G.H. et al. Betaine-homocysteine methyltransferase (BHMT): Genomic sequencing and relevance to hyperhomocysteinemia and vascular disease in humans // Mol. Genet. Metab. -2000. - Vol. 71, № 3. - P. 511-519.
30.
31. Allen R.H., Stabler S.P., Savage D.G., Lindenbaum J. Metabolic abnormalities in cobalamin (vitamin B12) and folate defi ciency // Faseb J. -1993. - Vol. 7, № 14. - P. 1344-1353.
32.
33. Puddu P., Puddu G.M., Cravero E. et al. The putative role of mitochondrial dysfunction in hypertension // Clin. Exp. Hypertens. - 2007. -Vol. 29, № 7. - P. 427-434.
Review
For citations:
Zhloba A.A., Mayevskaya E.G. The dysfunction of anaplerotic pathway of energy metabolism from amino acids to succinate in the elderly. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2011;17(1):74-78. (In Russ.) https://doi.org/10.18705/1607-419X-2011--1 -
Views:
665
Email this article 