2-ketoglutaric dehydrogenase

Vitamin Bi (thiamine) Mainly acts as Thpp (thiamine py-rc hosphate), a prosthetic group for 2-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase. Examples ... 

KD (K2) PDH El from eukaryotes and Gram-positive bacteria, branched-chain 2-ketoacid dehydrogenase El from human, 2-ketoglutarate dehydrogenase El, and acetoin dehydrogenase... 

Methy Icroto nylglydnur ia 3-Methylglutaconic aciduria, other types 3-Hydroxy-3 methylglutanyl CoA synthase def. 3-Hydroxy-3-methylglutanyl-CoA lyase def. HIHA-syndrome (hyper insulin ism + hyperammonemia) Methylmalonic acidemia 2-Ketoglutarate dehydrogenase complex def. 

Hydroxyisobutyric aciduria 2-Ketoglutarate dehydrogenase complex def. Fumarase def. 

The 2-ketoglutarate dehydrogenase (2-KGD) complex is composed of three separate enzymes 2-ketoglutarate decarboxylase, or El lipoate succi-nyltransferase, or E2 and lipoamide dehydrogenase, or E3. The complex catalyses the oxidation of 2-ketoglutarate to yield succinyl-CoA and NADH. 2-KGD deficiency together with pyruvate dehydrogenase deficiency and branched chain ketoacid decarboxylase deficiency has been ascribed to E3 deficiency because the three enzyme complexes have the E3 component in common. E3 deficiency will not be discussed. 

Fig. 8.1. Pathways of 2-ketoglutarate, fumarate, malonate and N-acetylaspartate metabolism and proposed pathways of D- and L-2-hydroxyglutarate metabolism. 8.1, 2-Ketoglutarate dehydrogenase complex (El or E2) 8.2, fumarase 8.3, malonyl-CoA decarboxylase 8.6, aspartoacylase...

Guffon N, Lopez-Mediavilla C, Dumoulin R et al. 2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia report of a new case. / Inker Metab Dis 1993 16 821-830... 

Mode of Action. The fundamental biochemical lesion produced by arsenicals is the result of reaction between As " and the sulfhydryl groups of key respiratory enzymes such as pymvate and a-ketoglutarate dehydrogenases. 

Lipoic acid is an acyl group carrier. It is found in pyruvate dehydrogenase zard a-ketoglutarate dehydrogenase, two multienzyme complexes involved in carbohydrate metabolism (Figure 18.34). Lipoie acid functions to couple acyl-group transfer and electron transfer during oxidation and decarboxylation of a-keto adds. 

Lsocitrate Dehydrogenase—The First Oxidadon in die Cycle m-Ketoglutarate Dehydrogenase—A Second Decarboxylation Succinyl-CoA Synthetase—A Substrate-Level Phosphoryladon Succinate Dehydrogenase—An Oxidadon Involving FAD... 

AceCyl-CoA + oxaloacetate + HgO. CoASH + citrate 2. Citrate. isocitrate 3. Isocitrate + NAD. a-ketoglntarate + NADH + CO, + 4. a-Ketoglntarate + CoASH + NAD. snccinyl-CoA + NADH + CO, + H Citrate synthase Aconitase Isocitrate dehydrogenase u-Ketoglutarate dehydrogenase complex... 

Composition of the n-Ketoglutarate Dehydrogenase Complex from E. coli ... 

Several enzymes of the intermediary metabolism require thiaminpyrophosphate (TPP, Fig. 1) as coenzyme, e.g., enzymes of the pyruvate dehydrogenase complex, a-ketoglutarate dehydrogenase complex, or pentose phosphate pathway. 

Pyruvate and a-ketoglutarate dehydrogenase have complex systems involving lipoate and FAD prior to the passage of electrons to NAD, while electron trans-... 

Four of the B vitamins are essential in the citric acid cycle and therefore in energy-yielding metabolism (1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor in the a-ketoglutarate dehydrogenase complex and in succinate dehydrogenase (2) niacin, in the form of nicotinamide adenine dinucleotide (NAD),... 

B, Thiamin Coenzyme in pyruvate and a-ketoglutarate, dehydrogenases, and transketolase poorly defined function in nerve conduction Peripheral nerve damage (beriberi) or central nervous system lesions (Wernicke-Korsakoff syndrome)... 

Diaz, F. and Komuniecki, R.W. (1996) Characterization of the alpha-ketoglutarate dehydrogenase complex from Fasciola hepatica potential implications for the role of calcium in the regulation of helminth mitochondrial metabolism. Molecular and Biochemical Parasitology 81,243—246. 

A somewhat more trivial thing to remember about the HMP pathway is that this is one of the places you ve seen the vitamin thiamin pyrophosphate. This cofactor is necessary for the transketolase reaction that is in the middle of the HMP pathway. The transketolase reaction converts two C-5 sugars to a C-7 and a C-3. The other place you ve seen thiamin pyrophosphate as a cofactor is in the pyruvate dehydrogenase and a-ketoglutarate dehydrogenase reactions. 

Thiamine deficiency results in early decreases in activity of the mitochondrial enzyme a-ketoglutarate dehydrogenase in brain. Wernicke s encephalopathy, also known as the Wernicke-Korsakoff syndrome is a neuropsychiatric disorder characterized by ophthalmoplegia, ataxia and memory loss. Wernicke s encephalopathy is encountered in chronic alcoholism, in patients with HIV-AIDS and in other disorders associated with grossly impaired nutritional status. The condition results from thiamine deficiency. 

This is not the only example of Nature inventing the assembly line a long time before Henry Ford—both pyru-vate dehydrogenase and a-ketoglutarate dehydrogenase, mentioned earlier in the chapter, are also multi-enzyme complexes. 

There are some very interesting questions of stereospecificity posed by the structure and mode of operation of multienzyme complexes. Reed and Cox 35> have summarized available information on the pyruvate and a-ketoglutarate dehydrogenase complexes, and the fatty add synthetase. The mechanism of synthesis of the peptide antibiotics likewise presents interesting stereochemical problems 36>. 

Pantothenic acid CoA i Fatty acid synthase Fatty acyl CoA synthetase Pyruvate dehydrogenase ci-Ketoglutarate dehydrogenase Fatty acid metabolism PDH TCA cycle Rare... 

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