Pyruvate dehydrogenase complex, function

Mitochondria from body wall muscle and probably the pharynx lack a functional TCA cycle and their novel anaerobic pathways rely on reduced organic acids as terminal electron acceptors, instead of oxygen (Saz, 1971 Ma et al, 1993 Duran et al, 1998). Malate and pyruvate are oxidized intramitochondrially by malic enzyme and the pyruvate dehydrogenase complex, respectively, and excess reducing power in the form of NADH drives Complex II and [3-oxidation in the direction opposite to that observed in aerobic organelles (Kita, 1992 Duran et al, 1993 Ma et al,... 

In summary, it is clear that A. suum undergoes a number of metabolic transitions during development and, in the case of the pyruvate dehydrogenase complex at least, is constantly fine-tuning the subunit-specific expression and function of the PDC during the course of development. 

Lipoic acid (the other names are a-lipoic acid or thioctic acid) (Figure 29.9) is a natural compound, which presents in most kinds of cells. Lipoic acid (LA) is contained in many food products, in particular in meat, but it is also synthesized in human organism from fatty acids. Earlier, it has been shown that in humans lipoic acid functions as a component of the pyruvate dehydrogenase complex. However, later on, attention has been drawn to the possible antioxidant activity of the reduced form of lipoic acid, dihydrolipoic acid (DHLA) (Figure 29.9). 

Coenzymes The pyruvate dehydrogenase complex contains five coenzymes that act as carriers or oxidants for the intermediates of the reactions shown in Figure 9.3. Ei requires thiamine pyrophosphate, Ep requires lipoic acid and coenzyme A, and E3 requires FAD and NAD+. [Note Deficiencies of thiamine or niacin can cause serious central nervous system problems. This is because brain cells are unable to produce sufficient ATP (via the TCA cycle) for proper function if pyruvate dehydrogenase is inactive.]... 

Zhou ZH, McCarthy DB, O Connor CM, et al. The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes.Proc Natl Acad Sci USA 98 14802-14807, 2001. 

Czerniecki J and Czygier M (2001) Cooperation of divalent ions and thiamin diphosphate in regulation of the function of pig heart pyruvate dehydrogenase complex. Joumai of Nutritionai Scence and Vitaminoiogy (Tokyo) 47,385-6. 

Pyruvate must first be transported into mitochondria by a specific carrier that cotransports a proton to maintain electrical neutrality. Inside mitochondria pyruvate undergoes oxidative decarboxylation by three enzymes that function sequentially and are present as a complex known as the pyruvate dehydrogenase complex. The overall reaction is physiologically irreversible, has a high negative AG° (—8.0 kcal/mol, or —33.5 kJ/mol), and commits pyruvate to the formation of acetyl-CoA ... 

E2 is a catalytic activity found in the pyruvate dehydrogenase complex. It forms the core of the complex. 24 copies of E2 are found in the complex isolated from Azotobacter. E2 is covalently bound to lipoic acid, forming lipoamide. Lipoamide functions to oxidize the aldehyde moiety transferred to it from El to an acetyl group and to subsequently transfer it to coenzyme A, forming acetyl-CoA. 

Kozak, B.U., van Rossum, H.M., Lutdk, M.A.H., Akeroyd, M. et al. (2014) Engineering acetyl coenzyme A supply functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae. MBio, 5, e01696-14. 

Pyruvate Dehydrogenase Complex (PDHc) 1,2,1 Function of PDHc... 

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. 

In the oxidative branch of malate dismutation, malic enzyme oxidizes malate to pyruvate, which is then further oxidized to acetyl-CoA by pyruvate dehydrogenase, an enzyme complex specially adapted to anaerobic functioning in Ascaris suum and possibly in other parasitic helminths like the trematode F. hepatica and the cestode Dipylidium caninum (Diaz and Komuniecki, 1994 Klingbeil et al., 1996). Parasitic helminths like F. hepatica use an acetate succinate CoA-transferase (ASCT) for... 

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