Acyl CoA dehydrogenase and electron-transferring flavoprotein

Hall, C.L., Lamheth, ID. Kamin, H. (1979)7. Biol. Chem. 254, 2023-2031. Acyl-CoA complexes of general acyl-CoA dehydrogenase and electron transferring flavoprotein. 

FIGURE 9.2 Physiology of ABE fermentation metabolism of Clostridium acetobutylicum with the respective enzymes and products. CoA, coenzyme A Ldh, lactate dehydrogenase Pdc, pyruvate decarboxylase Pfor, pyruvate ferredoxin oxidoreductase Fdred, ferredoxin reduced Thl, thiolase Hbd, p-hydroxybutyryl-CoA dehydrogenase Crt, crotonase Bed, butyryl-CoA dehydrogenase Etf, electron transfer flavoprotein Pta, phosphotransacetylase Ack, acetate kinase Ptb, phosphotransbutyrylase Buk, butyrate kinase Ctf A/B, acetoacetyl-CoA acyl-CoA transferase Adc, acetoacetate decarboxylase AdhE, aldehyde/alcohol dehydrogenase Bdh, butanol dehydrogenase. 

Nishida, N., Sugimoto, T., Araki, A., Woo, M., Sakane, Y. Kobayashi, Y. (1981) Pediatr. Res. 22, 500-503. Carnitine metabolism in valproate-treated rats The effect of L-Camitine supplementation. Nagao, M., Parimoo, B. Tanaka, K. (1993) J. Biol Chem 268, 24114-24124. Developmental, nutritional, and hormonal regulation of tissue-specific expression of the genes encoding various acyl-CoA dehydrogenases and a-subunit of electron transfer flavoprotein in rat. 

Figure 37.2 Cartoon depicting enzymes participating in mitochondrial P-oxidation and part of the respiratory chain. Acyl-CoA substrates derived from fatty acid and amino acid metabolism are oxidized by several flavin-containing acyl-CoA dehydrogenases (ACAD). Electrons obtained from this reaction are shuttled to the respiratory chain via the ETF/ETF QO hub (electron-transfer flavoprotein and electron-transfer flavoprotein ubiquinone oxidoreductase). ETF QO is able to transfer electrons to ubiquinone (Q) (such as respiratory complexes I and II) whose subsequent transfer down to complex IV will result in energy conservation and ATP production. See list of abbreviations for definitions.

Nagao, M., and Tanaka, K., 1992. FAD-dependent regulation of transcription, translation, post-translational processing, and post-processing stability of various mitochondrial acyl-CoA dehydrogenases and of electron transfer flavoprotein and the site of holoenzyme formation. The Journal of Biological Chemistry. 267 17925-17932. 

A distinct electron transfer flavoprotein (ETF) is the single-electron acceptor for a variety of flavoprotein dehydrogenases, including acyl CoA, glutaryl CoA, sarcosine, and dimethylglycine dehydrogenases. It then transfers the electrons to ETF-ubiquinone reductase, the iron-sulfur flavoprotein that reduces ubiquinone in the mitochondrial electron transport chain. 

Electrons from succinate are transferred to FAD in complex n and several Fe-S centers and then to UQ. Electrons from cytoplasmic NADH are transferred to UQ via a pathway involving glycerol-3-phosphate and the flavoprotein glycerol-3-phosphate dehydrogenase (see p. 316). Fatty acids are oxidized as coenzyme A derivatives. Acyl-CoA dehydrogenase, one of several enzymes in fatty acid oxidation, transfers 2 electrons to FAD. They are then donated to UQ. 

Like the FAD in all flavoproteins, FAD(2H) bound to the acyl CoA dehydrogenases is oxidized back to FAD without dissociating from the protein (Fig. 23.8). Electron transfer flavoproteins (RTF) in the mitochondrial matrix accept electrons from the enzyme-bound FAD(2H) and transfer these electrons to ETF-QO (electron transfer flavoprotein -CoQ oxidoreductase) in the inner mitochondrial membrane. ETF-QO, also a flavoprotein, transfers the electrons to CoQ in the electron transport chain. Oxidative phosphorylation thus generates approximately 1.5 ATP for each FAD(2H) produced in the (3-oxidation spiral. 

Fig. 13.1.1. Schematic overview of mitochondrial oxidative phosphorylation. A part of the mitochondrion is represented, showing the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM) and crista (an invagination of the inner membrane). Substrates for oxidation enter the mitochondrion through specific carrier proteins, e.g., the pyruvate transporter, (PyrT). Reducing equivalents from fatty acyl CoA dehydrogenases, pyruvate dehydrogenase and the TCA cycle are delivered to the electron transport chain through NADH, succinate ubiquinol oxidoreductase (SQO), electron transfer flavoprotein (ETF) and its ubiquinol-...

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