Flavin adenine dinucleotide metabolism

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),... 

Riboflavin fulfills its role in metabolism as the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) (Figure 45-10). FMN is formed by ATP-dependent phosphorylation of riboflavin, whereas FAD is synthesized by further reaction of FMN with ATP in which its AMP moiety is transferred to the... 

Xun L, ER Sandvik (2000) Characterization of 4-hydroxyphenylactate 3-hydroxylase (HpaB) of Escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase. Appl Environ Microbiol 66 481-486. Zaar A, J Gescher, W Eisenreich, A Bacher, G Fuchs (2004) New enzymes involved in aerobic benzoate metabolism m Azoarcus evansii. Mol Microbiol 54 223-238. 

FIGURE 32-7 Sources of free radical formation which may contribute to injury during ischemia-reperfusion. Nitric oxide synthase, the mitochondrial electron-transport chain and metabolism of arachidonic acid are among the likely contributors. CaM, calcium/calmodulin FAD, flavin adenine dinucleotide FMN, flavin mononucleotide HtT, tetrahydrobiopterin HETES, hydroxyeicosatetraenoic acids L, lipid alkoxyl radical LOO, lipid peroxyl radical NO, nitric oxide 0 "2, superoxide radical. 

Disulfoton causes neurological effects in humans and animals. The mechanism of action on the nervous system depends on the metabolism of disulfoton to active metabolites. The liver is the major site of metabolic oxidation of disulfoton to disulfoton sulfoxide, disulfoton sulfone, demeton S-sulfoxide and demeton S-sulfone, which inhibit acetylcholinesterase in nervous tissue. These four active metabolites are more potent inhibitors of acetylcholinesterase than disulfoton. Cytochrome P-450 monooxygenase and flavin adenine dinucleotide monooxygenase are involved in this metabolic activation. The active metabolites ultimately undergo nonenzymatic and/or enzymatic hydrolysis to more polar metabolites that are not toxic and are excreted in the urine. 

In the second stage, the building blocks are degraded by various pathways in tissues to a common metabolic intermediate, acetyl CoA. Most of the energy contained in metabolic fuels is conserved in the chemical bonds (electrons) of acetyl CoA. A smaller portion is conserved in reducing nicotinamide adenine dinucleotide (NAD) to NADH or flavin adenine dinucleotide (FAD) to FADH. Reduction indicates the addition of electrons that may be free, part of a hydrogen atom (H), or a hydride ion (H ). 

So what does riboflavin do As such riboflavin does nothing. Like thiamine, riboflavin must undergo metabolic change to become effective as a coenzyme. It fact, it undergoes two reactions. The first converts riboflavin to riboflavin-5-phosphate (commonly known as flavin adenine mononucleotide, FMN), about which we will say no more, and the second converts it to flavin adenine dinucleotide, FAD. The flavins are a class of redox agents of very general importance in biochemistry. FAD is the oxidized form and FADH2 is the reduced form. ... 

Figure 9.6 Sequence of electron carriers in the electron transfer chain. The positions of entry into the chain from metabolism of glucose, glutamine, fatty acyl-CoA, glycerol 3-phosphate and others that are oxidised by the Krebs cycle are shown. The chain is usually considered to start with NADH and finish with cytochrome oxidase. FMN is flavin mononucleotide FAD is flavin adenine dinucleotide.

Riboflavin (vitamin B2) is a component of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), coenzymes that play a major role in oxidation-reduction reactions (see Section 15.1.1). Many key enzymes involved in metabolic pathways are actually covalently bound to riboflavin, and are thus termed flavoproteins. 

Riboflavin (from the Latin flavus, yellow) serves in the metabolism as a component of the redox coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD see p. 104). As prosthetic groups, FMN and FAD are cofactors for various oxidoreductases (see p. 32). No specific disease due to a deficiency of this vitamin is known. 

Riboflavin (B2) Flavin adenine dinucleotide flavin mononucleotide Carbohydrate metabolism... 

Fig. 1. Energy metabolism in the normal myocardium (ATP adenosine-5 -triphosphate, ADP adenosine-5 -diphosphate, P phosphate, PDH pyruvate dehydrogenase complex, acetyl-CoA acetyl-coenzyme A, NADH and NAD" nicotinamide adenine dinucleotide (reduced and oxidized), FADH2 and FAD flavin adenine dinucleotide (reduced and oxidized).

Vitamin Bj (8.44, riboflavin) is a benzopteridine derivative carrying a ribityl (reduced ribose) side chain. It occurs in almost all foods, the largest amounts being found in eggs, meat, spinach, liver, yeast, and milk. Riboflavin is one of the major electron carriers as a component of flavine-adenine dinucleotide (FAD), which is involved in carbohydrate and fatty acid metabolism. A hydride ion and a proton are added to the pyrazine ring of... 

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...

Riboflavin (vitamin B2 6.18) consists of an isoalloxazine ring linked to an alcohol derived from ribose. The ribose side chain of riboflavin can be modified by the formation of a phosphoester (forming flavin mononucleotide, FMN, 6.19). FMN can be joined to adenine monophosphate to form flavin adenine dinucleotide (FAD, 6.20). FMN and FAD act as co-enzymes by accepting or donating two hydrogen atoms and thus are involved in redox reactions. Flavoprotein enzymes are involved in many metabolic pathways. Riboflavin is a yellow-green fluorescent compound and, in addition to its role as a vitamin, it is responsible for the colour of milk serum (Chapter 11). 

Figure 21-2. Metabolism of homocysteine. BHMT, betaineihomocysteine methyl-transferase CBS, cystathionine P-synthase Cob, cobalamin CTH, cystathionine y-lyase DHF, dihydrofolate DMG, dimethylglycine FAD, flavin adenine dinucleotide MAT, methionine adenosyltransferase 5-MTHF, 5-methyltetrahydrofolate 5,10-MTHF, 5,10-methylenetetrahydrofolate MTHFR, methylenetetrahydrofolate reductase MS, methionine synthase MTRR, methionine synthase reductase MTs, methyl transferases PLE pyridoxal phosphate SAH, S-adenosylhomocysteine SAHH, SAH hydrolase SAM, 5-adenosylmethionine SHMT, serine hydroxymethyltransferase THF, tetrahydrofolate Zn, zinc.

Nucleotides are stmctural units of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and cofactors such as coenzyme A (CoA), flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), with important roles in energy transfer, metabolism and intracellular signalling. 

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. 

As shown in Figure 7.1, riboflavin consists of a tricyclic dimethyl-isoalloxazine ring conjugated to the sugar alcohol ribitol. The metabolically active coenzymes are riboflavin 5 -phosphate and flavin adenine dinucleotide (FAD). In some enzymes the prosthetic group is riboflavin, bound covalently at the catalytic site. 

Most of the electrons removed from fuels during energy metabolism are transferred via nicotinamide adenine dinucleotide (NAD). NAD collects electrons from many different energy fuels in reactions catalyzed by specific enzymes. These enzymes are dehydrogenases. Reduced NAD, in turn, shuttles the electrons to the respiratory chain. Flavin adenine dinucleotide (FAD) also acts as an electron shuttle. In each reaction involving NAD (or FAD), two electrons are transferred that is, two electrons are carried or shuttled. NAD and FAD are small molecules with molecular weights of 663 and 785 and are manufactured in the body from the vitamins niacin and riboflavin, respectively. These molecules are called N.A.D. and F.A.D., not nad" or Jad. ... 

In higher mammals, riboflavin is absorbed readily from the intestines and distributed to all tis.sues. It is the precursor in the biosynthesis of the cocnzyme.s flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The metabolic functions of this vitamin involve these Iwocoenzymes. which participate in numerous vital oxidation-reduction proces.ses. FMN (riboflavin 5 -phosphate) is produced from the vitamin and ATP by flavokinasc catalysis. This step con be inhibited by phcnothiazincs and the tricyclic antidepressants. FAD originates from an FMN and ATP reaction that involves reversible dinucicotide formation catalyzed by flavin nucleotide pyrophosphorylase. The.se coenzymes function in combination with several enzymes as coenzyme-en-zyme complexes, often characterized as, flavoproteins. 

Vitamin B complex is the collective term for a number of water-soluble vitamins found particularly in dairy products, cereals and liver.Vitamin B (thiamine) is used by mouth for dietary supplement purposes and by injection in emergency treatment of Wernicke-Korsakoff syndrome. Vitamin B2 (riboflavin) is a constituent of the coenzyme FAD (flavine adenine dinucleotide) and FMN (flavine mononucleotide) and is therefore important in cellular respiration. Vitamin Be (pyridoxine) is a coenzyme for decarboxylases and transamination, and is concerned with many metabolic processes. Overdose causes peripheral neuropathy. It may be used medically for vomiting and radiation sickness and for premenstrual tension. Pyridoxine has a negative interaction with the therapeutic use of levodopa in parkinsonism by enhancing levodopa decarboxylation to dopamine in the periphery, which does not then reach the brain. The antitubercular drug isoniazid interferes with pyridoxine, and causes a deficiency leading to peripheral neuritis that may need to be corrected with dietary supplements. Vitamin B ... 

Coenzymes - Many enzymes require nonprotein coenzymes for catalytic activity.8 These are cosubstrates, and must be constantly reconverted into their active form for catalysis to continue. This is not a problem for growing microorganisms since the normal metabolic processes ensure an adequate supply of coenzymes. However, with purified, or immobilized enzymes, maintaining a sufficient concentration of coenzyme can pose a major problem. Coenzymes are expensive and it is seldom economically feasible to add them in stoichiometric amounts. This is often undesirable for chemical reasons, e.g., the coenzyme may be unstable, or the eventual build-up of high concentrations of its inactive form may Induce displacement of an equilibrium reaction in the opposite direction to that desired.3 It is therefore necessary to use catalytic amounts of coenzymes and to ensure that the active forms are continuously regenerated. Some coenzymes present little or no problem in this regard since they are automatically reformed under the normal aqueous reaction conditions or in the presence of oxygen. These include biotin, pyrldoxal phosphate (PLP), thiamine pyrophosphate, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).1 ... 

Whereas redox reactions on metal centres usually only involve electron transfers, many oxidation/reduction reactions in intermediary metabolism, as in the case above, involve not only electron transfer, but hydrogen transfer as well — hence the frequently used denomination dehydrogenase . Note that most of these dehydrogenase reactions are reversible. Redox reactions in biosynthetic pathways usually use NADPH as their source of electrons. In addition to NAD and NADP+, which intervene in redox reactions involving oxygen functions, other cofactors like riboflavin (in the form of flavin mononucleotide, FMN, and flavin adenine dinucleotide, FAD) (Figure 5.3) participate in the conversion of [—CH2—CH2— to —CH=CH—], as well as in electron transfer chains. In addition, a number of other redox factors are found, e.g., lipoate in a-ketoacid dehydrogenases, and ubiquinone and its derivatives, in electron transfer chains. 

BMR Basal metabolic rate FAD Flavin adenine dinucleotide (oxidized)... 

Flavin adenine dinucleotide (FAD) and its reduced form dihydroflavin (FADHj) participate in a large number of oxidation/reduction reactions in metabolism . The structure of the reduced form has a distinct enamine feature that has been hypothesized to participate in covalent bonds with a number of substrates. 

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