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ALDH

Aldehyde dehydrogenases (ALDHs) belong to a superfamily of enzymes that play a key role in the metabolism of aldehydes of both endogenous and exogenous derivation. The aldehyde dehydrogenases (ALDHs) have a surprisingly broad spectrum of biological activities. ALDH activity is crucial to the biosynthesis of retinoic acid, an important regulator of vertebrate development, and to the metabolism of the neurotransmitter GABA.The human ALDH superfamily comprises 19 known NAD(P+)-dependent enzymes that irreversibly catalyze the oxidation of both endogenously and exogenously produced aldehydes to their respective carboxylic acids.ALDH2, as a key enzyme that oxidizes acetaldehyde, is crucial for alcohol metabolism. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissues. Only three ALDH isozymes, ALDH1A1, ALDH2, and ALDH3A1, have been studied for vulnerability to pharmacological inhibition. No antagonists have been developed that inhibit each ALDH isozyme without affecting the others. This lack of selectivity of available antagonists for specific ALDH isozymes has not prevented clinical usage, so the emergence of ALDH isozymes as potentially important therapeutic targets serves as an impetus for the need for the development of selective inhibitors.

References

1.Vindhya Koppaka,et al. Pharmacol Rev. 2012 Jul; 64(3): 520–539.

Metabolic Enzyme/Protease

11β-HSD(15) 15-PGDH(1) ACC(10) ACE(9) AChE(29) Adenylate Cyclase(10) ALDH(14) Aldose Reductase(5) Aminopeptidase(17) BACE(18) Casein Kinase(41) CAT(5) Cathepsin(8) CETP(10) COMT(2) CPG2(1) CYPs(6) Decarboxylase(3) Dehydrogenase(87) DGAT(4) Dopamine beta-hydroxylase(2) DPP(28) Elastase(6) FAAH(19) Factor Xa(22) Fatty Acid Synthase(16) Ftase(2) FXR(22) Glucokinase(1) GSNOR(2) Guanylate Cyclase(9) HMGCR(17) IDH(7) IDO(20) IMPDH(2) LDH(2) LDL(5) Lipase(13) Lipid(9) MAGL(3) MAO(51) MMP(48) NAMPT(7) Neprilysin(6) Other Targets(9) P450(87) PAI-1(7) Phosphatase(49) Phospholipase(43) PPAR(86) Protein Phosphatase/PTP(6) Renin(7) Retinoid Receptor(23) SCD(6) Steroid Sulfatase (STS)(2) Thioredoxin(1) TPH(5) Transferase(24) Vitamin(39) Xanthine Oxidase (XAO)(6)