Mitochondrial aldehyde dehydrogenase

A recent publication from Stamler and colleagues [95, 96] identified mitochondrial aldehyde dehydrogenase (mtALDH) as a key enzyme in GTN metabolism. The au- 

Regarding the vasculature, treatment of aortic rings with mtALDH inhibitors attenuated GTN-dependent relaxation, formation of 1,2-GDN and accumulation of cGMP. Moreover, when tolerance was induced by pre-treatment with GTN, generation of 1,2-GDN and cGMP were again decreased, as was the activity of mtALDH. In whole animals, ALDH inhibitors were shown to attenuate the hypotensive effects of GTN in rabbits and rats. 

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In some Asian populations and Native Americans, alcohol consumption results in increased adverse reactions to acetaldehyde owing to a genetic defect of mitochondrial aldehyde dehydrogenase. 

Steinmetz CG, Xie P, Weiner H, Hurley TD. Structure of mitochondrial aldehyde dehydrogenase The genetic component of alcohol aversion. Structure 1997 5 701-711. 

Zhou J, Weiner H. Basis for half-of-the-sites reactivity and the dominance of the K487 oriental subunit over the E487 subunit in heterotetrameric human liver mitochondrial aldehyde dehydrogenase. Biochemistry 2000 39 12019-12024... 

Hsu LC, Bendel RE, Yoshida A. Genomic structure of the human mitochondrial aldehyde dehydrogenase gene. Genomics 1988 2 57-65. 

Chou W-Y, Stewart MJ, Carr LG, Zheng D, Stewart TR, Williams A, Pinaire J, Crabb DW. An A/G polymorphism in the promoter of mitochondrial aldehyde dehydrogenase (ALDH2) effects of the sequence variant on transcription factor binding and promoter strength. Alcohol Clin Exp Res 1999 26 963-968. 

N. Mukerjee, R. Peitruszko, Human Mitochondrial Aldehyde Dehydrogenase Substrate Specificity-Comparison of Esterase with Dehydrogenase Reaction , Arch. Biochem. Biophys. 1992, 299, 23-29. 

A very high activity of mitochondrial aldehyde dehydrogenases (together with its low ensures very efficient oxidation in the liver so that the concentration of acetaldehyde in blood remains very low. Nonetheless, it is possible that some of the pathological effects of ethanol are due to acetaldehyde (ethanal). In contrast, a large proportion of the acetate escapes from the liver and is converted to acetyl-CoA by acetyl-CoA synthetase in other tissues ... 

Cytoplasmic and mitochondrial aldehyde dehydrogenases (from beef liver) have also been inactivated by the hydrate 21 [21]. 

After 2- days of repeated NG exposure, tolerance to the vasodilatory activity occurs, probably as a result of compensatory vasoconstriction. Tolerance may be lost during periods without NG exposure, such as weekends and holidays. Recent smdies have suggested that tolerance may be mediated by a mitochondrial aldehyde dehydrogenase that catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from NG, leading to production of cGMP and relaxation of vascular smooth muscle. ... 

Chen Z, Stamler, JS Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase. Trends Cardiovasc Med 2006 16 259. [PMID 17055381]... 

Goedde and Agarwal (96) list test results from 29 different populations and a total of 3248 subjects. The data can be summarized by the statements that Central Asian, East Asian, and South-East Asian populations showed deficiencies in the order of 30%. The deficiency was absent in European, Near-East, and African populations. North American Indians showed deficiency rates of 2-5%, South American Indians of 40-45%. O Dowd et al. (101) have shown that the functional enzyme deficiency in South American Indians must be due to a different mutation than the deficiency in Asians. This observation raises interesting questions regarding the biological significance of the mitochondrial aldehyde dehydrogenase. 

Hempel J, Kaiser R, Jdmvall H. Mitochondrial aldehyde dehydrogenase from human liver primary structure, differences in relation to the cytosolic enzyme and functional correlations. Eur J Biochem 1985 153 13-28. 

O Dowd BF, Rothhammer F, Israel Y. Genotyping of mitochondrial aldehyde dehydrogenase locus of native American Indians. Alcohol Clin Exp Res 1990 14 531-533. 

Novoradovsky A, Tsai SJ, Goldfarb L, Peterson R, Long JC, Goldman D. Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations detection of new ALDH2 alleles. Alcohol Clin Exp Res 1999 19 1105-1110. 

Retrive nucleotide sequence encoding mRNA of human mitochondrial aldehyde dehydrogenase 2 (ALDH 2 gil 1436532) and carry out gene identification with GeneMark. 

The enzymatic mechanisms of nitrate bioactivation have long been the subject of debate. The glutathione-S-transferase and cytochrome P-450 systems were thought to be involved [8], while recently a nitrate reductase that specifically catalyzes the formation of 1,2-glyceryl dinitrate from glyceryl trinitrate was purified and identified as a mitochondrial aldehyde dehydrogenase [46]. Interestingly, this... 

Hexogen (RDX) was first prepared in 1899 by Henning for medicinal use. (N.B. NG and PETN are also used in medicine to treat angina pectoris. The principal action of these nitrate esters is vasodilation (i.e. widening of the blood vessels). This effect arises because in the body the nitrate esters are converted to nitric oxide (NO) by mitochondrial aldehyde dehydrogenase, and nitric oxide is a natural vasodilator.) In 1920 Herz prepared RDX for the first time by the direct nitration of hexamethylene tetramine. Shortly afterwards Hale (Picatinny Arsenal, NJ) developed a process that formed RDX in 68 % yield. The two processes most widely used in WW II were... 

Kamino K, Nagasaka K, Imagawa M, Yamamoto H, Yoneda H, Held A, Kitamura S, Ntimekata K, Miki T, Ohta S (2000) Deficiency in mitochondrial aldehyde dehydrogenase increases the risk for late-onset Alzheimer s disease in the Japanese population. Biochem Biophys Res Commun 273 192-196... 

Alcohol dehydrogenase, a cytosolic enzyme, catalyzes the oxidation of ethanol to acetaldehyde with the generation of NADH. The energy from this NADH is transferred to mitochondria, primarily by means of the malate-aspartate shuttle. When an alcoholic consumes over 50% of his or her energy in the form of alcohol, this shuttle becomes vastly important. Most of the acetaldehyde is oxidized in the mitochondria by mitochondrial aldehyde dehydrogenase, though a cytosolic version of the enzyme also exists. These reactions are shown in Figure 4.69. 

Biotransformations of nitroglycerin, (a) Normal mechanism of aldehyde reductase (b) production of nitrite by mitochondrial aldehyde dehydrogenase. 

KlyosovAA, Rashkovetsky LG, Tahir MK, KeungW-M (1996) Possible role of liver cytosolic and mitochondrial aldehyde dehydrogenases in acetaldehyde metabolism. Biochemistry 35 4445-4456... 

TSUJI, H., TSUTSUMI, N., SASAKI, T., HIRAI, A., NAKAZONO, M., Organ-specific expressions and chromosomal locations of two mitochondrial aldehyde dehydrogenase genes from rice Oryza sativa L.), ALDH2a and ALDH2b, Gene, 2003,305, 195-204. 

Keung WM, Klyosov AA, Vallee BL. Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters. Proc Natl Acad Sci USA 1997 94 1675-9. 

S. Stamler, Pwc. Nat. Acad. Sci, 102, 2005, 12159-12164. (Mitochondrial aldehyde dehydrogenase activates nitroglycerine)... 

K. Sydow, A. Daiber, M. Oelze, Z. Chen, M. August, M. Wendt, V. Ullrich, A. Mnelsch, E. Schulz, J. F. Keaney Jr., J. S. Stamler and T. Muenzel. Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance. J. Clin. Invest. 113, 2004,482—489. 

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