Flavin adenine dinucleotide fatty acid oxidation

A saturated acyl CoA is degraded by a recurring sequence of four reactions oxidation by flavin adenine dinucleotide (FAD), hydration, oxidation by NAI), and thiolysis by coenzyme A (Figure 22.9). "Fhe fatty acid chain is shortened by two carbon atoms as a result of these reactions, and FADII., NADH, and acetyl CoA are generated. Because oxidation takes place at the P carbon, this series of reactions is called the oxidation pathway. 

Oxidation of pyruvate and fatty acids to CO2 coupled to reduction of NAD to NADH and of flavin adenine dinucleotide (FAD), another oxidized electron carrier, to its reduced form, FADH2 (see Figure 2-26). These electron carriers are often referred to as coenzymes. NAD, NADH, FAD, and FADH2 are diffusible and not permanently bound to proteins. Most of the reactions occur in the matrix two are catalyzed by inner-membrane enzymes that face the matrix. 

Step 1 of Figure 29.3 Introduction of a Double Bond The /3-oxidation pathway begins when a fait)7 acid forms a thioester with coenzyme A to give a fatty acyl Co A. Two hydrogen atoms are then removed from C2 and C3 of the fatty acyl CoA by one of a family of acyl-CoA dehydrogenases to yield an a,/3-unsaturated acyl CoA. This kind of oxidation—the introduction of a conjugated double bond into a carbonyl compound—occurs frequently jn biochemical pathways and usually involves the coenzyme flavin adenine dinucleotide (FAD). Reduced FADH2 is the by-product. 

Table 3.1.1 Disorders of organic acid metabolism (in alphabetical order). This table does not include disorders with primary accumulation of amino acids, disorders of mitochondrial fatty acid oxidation, or primary lactic acidemias. Co A Coenzyme A, FAD flavin adenine dinucleotide...

F26BP, fructose-2,6-bisphosphate FA, fatty acid FAD, fatty acid desaturase FADH2/FAD, reduced/oxidized flavin adenine dinucleotide F -ATPase, ATP synthetase F complex FGF, fibroblast growth factor FGF-RTK, fibroblast growth factor receptor tyrosine kinase Fmet, formylmethionine FMNH2/FMN, reduced/oxidized flavin mononucleotide... 

Subsequently, the functions of the vitamin were better established and requirements for the vitamin were set. Riboflavin is an Integral part of two coenzymes, flavin-5 -phosphate (FMN) and flavin adenine dinucleotide (FAD), which function in oxidation/reductlon reactions. Indeed, riboflavin is an enzyme cofactor which is necessary in metabolic processes in which oxidation of glucose or fatty acid is used for production of adenosine triphosphate (ATP) as well as in reactions in which oxidation of amino acids is accomplished. The minimum requirement for riboflavin has been established as that amount which actually prevents the signs of deficiency. A range of intakes varying from 0.55 to 0.75 mg/day of riboflavin has been established as the minimum amount which is required to prevent appearance of deficiency signs. 

The oxidation reactions involved are catalyzed by a series of nicotinamide adenine dinucleotide (NAD+) or flavin adenine dinucleotide (FAD) dependent dehydrogenases in the highly conserved metabolic pathways of glycolysis, fatty acid oxidation and the tricarboxylic acid cycle, the latter two of which are localized to the mitochondrion, as is the bulk of coupled ATP synthesis. Reoxidation of the reduced cofactors (NADH and FADH2) requires molecular oxygen and is carried out by protein complexes integral to the inner mitochondrial membrane, collectively known as the respiratory, electron transport, or cytochrome, chain. Ubiquinone (UQ), and the small soluble protein cytochrome c, act as carriers of electrons between the complexes (Fig. 13.1.1). 

Fatty acid beta-oxidation is depicted in Fig. 22.2. hi the first step, the acyl-CoA is oxidized by acyl-CoA dehydrogenase removing two hydrogens and transferring them to FAD (flavin adenine dinucleotide) resulting in 2,3-enoyl-CoA. The unsaturated bond is between atoms 2 and 3 on the beta-carbon. There are several different acyl-CoA dehydrogenases, which differ in the chain length specificity of their substrates. Short-chain... 

Riboflavin, commonly known as vitamin B2, is metabolized inside cells to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), two very important enzyme cofactors. These molecules possess rather unique and versatile chemical properties, which confer on them the ability to be among the most important redox cofactors found in a broad range of enzymes. In this chapter we provide a brief description of riboflavin metabolism and chemistry, overview the different flavoenzymes engaged in fatty acid p-oxidation and their respective roles. We also highlight recent studies shedding light on the cellular processes and biological effects of riboflavin supplementation in the context of metabolic disease. 

It is, however, better known that flavoenzymes (i.e., enzymes utilizing the flavin adenine dinucleotide [FAD FADH2] redox system) mediate the introduction of a,P carbon-carbon double bonds into carboxylic acids and into acetyl Coenzyme A (acetyl CoA) thioesters of long-, medium-, and short-chain fatty acids. In carboxylic acids, such as those of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11) the oxidation is affected by the enzyme sucdnate dehydrogenase (fumerate reductase— EC 1.3.99.1), which utilizes the cofactor flavin adenine dinucleotide (FAD) The latter is reduced to FADH2 and an ( )-double bond is introduced. The process shown in Scheme 9.105, for the conversion of succinate (1,4-butanedioic acid) to fumerate [(E)-l,4-butenedioic acid], is a fragment of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11), which is the pathway commonly utilized for oxidative degradation of acetate to carbon dioxide. 

FA, fatty acid FADHj, reduced form of flavine adenine dinucleotide GTP, guanosine triphosphate NADH, reduced form of nicotinamide adenine dinucleotide ATP, adenosine triphosphate NAD3 oxidized form of nicotinamide adenine dinucleotide FAD, flavine adenine dinucleotide TAG, triacylglycerol... 

Fig. 4.9. The fatty acid (/3-oxidation) spiral. Fatty acids are degraded to reduced NAD and FAD (flavin adenine dinucleotide) which can transfer electrons to the respiratory electron transport system, and acetyl-CoA which...

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