Flavins nucleotides

Coemymes effecting transfer of hydrogen. These include the pyridine nucleotides, nicotinamide-adenine dinucleolide and nicotinamide-adenine dinucleolide phosphate the flavin nucleotides such as flavin-adenine dinucleotide and lipoic acid. 

Hydrolases represent a significant class of therapeutic enzymes [Enzyme Commission (EC) 3.1—3.11] (14) (Table 1). Another group of enzymes with pharmacological uses has budt-ia cofactors, eg, in the form of pyridoxal phosphate, flavin nucleotides, or zinc (15). The synthases, and other multisubstrate enzymes that require high energy phosphates, are seldom available for use as dmgs because the required co-substrates are either absent from the extracellular space or are present ia prohibitively low coaceatratioas. 

The flavin nucleotides are typically involved in the oxidations creating double bonds from single bonds. The flavin takes up two hydrogen atoms, represented in the figure as being derived by transfer of hydride from the substrate and a proton from the medium. 

Selected entries from Methods in Enzymology [vol, page(s)] Determination of FMN and FAD by fluorescence titration with apoflavodoxin, 66, 217 purification of flavin-adenine dinucleotide and coenzyme A on p-acetoxymercurianiline-agarose, 66, 221 a convenient biosynthetic method for the preparation of radioactive flavin nucleotides using Clostridium kluyveri, 66, 227 isolation, chemical synthesis, and properties of roseoflavin, 66, 235 isolation, synthesis, and properties of 8-hydroxyflavins, 66, 241 structure, properties and determination of covalently bound flavins, 66, 253 a two-step chemical synthesis of lumiflavin, 66, 265 syntheses of 5-deazaflavins, 66, 267 preparation, characterization, and coenzymic properties of 5-carba-5-deaza and 1-... 

Like the nicotinamide coenzymes (Fig. 13-15), the flavin nucleotides undergo a shift in a major absorption band on reduction. Flavoproteins that are fully reduced (two electrons accepted) generally have an absorption maximum near 360 nm. When partially reduced (one electron), they acquire another absorption maximum at about 450 nm when fully oxidized, the flavin has maxima at 370 and 440 nm. The intermediate radical form, reduced by one electron, has absorption maxima at 380, 480, 580, and 625 nm. These changes can be used to assay reactions involving a flavoprotein. 

FMN consists of the structure above the dashed line on the FAD (oxidized form). The flavin nucleotides accept two hydrogen atoms (two electrons and two protons), both of which appear in the flavin ring system. When FAD or FMN accepts only one hydrogen atom, the semiquinone, a stable free radical, forms... 

Flavoproteins are often very complex some have, in addition to a flavin nucleotide, tightly bound inorganic ions (iron or molybdenum, for example) capable of participating in electron transfers. 

FAD and FMN, the flavin nucleotides, serve as tightly bound prosthetic groups of... 

Oxidative phosphorylation begins with the entiy of electrons into the respiratory chain. Most of these electrons arise from the action of dehydrogenases that collect electrons from catabolic pathways and funnel them into universal electron acceptors—nicotinamide nucleotides (NAD+ or NADP+) or flavin nucleotides (FMN or FAD). 

B Entsch, RG Sim. The purification and identification of flavin nucleotides by high-performance liquid chromatography. Anal Biochem 133 401-408, 1983. 

Answer The flavin nucleotides, FMN and FAD, would not be synthesized. Because FAD is required by the citric acid cycle enzyme succinate dehydrogenase, flavin deficiency would strongly inhibit the cycle. 

The study of bioenergetics involves the study of (1) the processes by which reduced nicotinamide and flavin nucleotides, generated primarily from the oxidation of carbohydrates (Chap. 11) and lipids (Chap. 13), are oxidized ultimately by molecular oxygen via the mitochondrial electron-transport chain, and (2) the mechanism by which this oxidation is coupled to ATP synthesis. The synthesis of ATP in this way is referred to as oxidative phosphorylation, in contrast to phosphorylation of ADP via soluble enzymes. The latter involves intermediate phosphate derivatives of the substrate and is known as substrate-level phosphorylation (Chap. 11). 

Muscle tissue contains two glycerol-3-phosphate dehydrogenases a cytosolic enzyme, which uses NADH, and a flavin-nucleotide-dependent mitochondrial enzyme. What is the metabolic significance of these two enzymes ... 

Nevertheless, several problems exist larger equipment is usually required, since relatively low productivities are generally achieved, although there are significant exceptions. But the main problem is that most biochemical oxidations require stoichiometric amounts of co-factors which are quite complex and expensive chemicals, such as flavins, nucleotides, etc, that Nature has developed. This is why it is usually easier to carry out oxidations not with isolated enzymes but rather with entire microorganisms able to produce by themselves the cofactors they need. 

Mizuno N, Nakayama F, Morita E. Photodecomposition of pyridoxine accelerated by flavine nucleotide. Vitamin 1979 53(5-6) 213-219. 

Typical biochemical hydrogenation (reduction) reactions are catalyzed by prosthetic enzymes with nicotinamide or flavin nucleotide as coenzyme. Model asymmetric hydrogenation of these types, however, await future stu s. 

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. 

The hydrogens are accepted by FAD, which is covalently bound to the apoprotein via a histidine residue. In many flavoproteins, the flavin nucleotide is bound to the apoprotein not covalently but rather via ionic linkages with the phosphate group. The reducing equivalents of FADH2 are passed on to coenzyme Q (CoQ or Q) via the iron-sulfur centers. Thus, the overall reaction catalyzed by complex II is... 

The tricarboxylic acid (TCA) cycle and yd-oxidation (Chapter 14) are tightly coupled to electron transport via the nicotinamide and flavin nucleotides and by ADP and ATP. The TCA cycle in cells functions only when ADP is present (i.e., when ATP is being utilized). Thus,... 

Conversion of dihydroorotate to orotate is catalyzed by dihydroorotate dehydrogenase, a metalloflavoprotein that contains nonheme-iron atoms and flavin adenine nucleotides (FMN and FAD). In this reaction, the electrons are probably transported via iron atoms and flavin nucleotides that are reoxidized by NAD+. 

The formation of succinate from fumarate by fumarate reductase (FR) and anaerobic phosphorylation of ADP to ATP are amongst the important reactions taking place in the mitochondria to provide energy to the helminths. The FR system of helminths differs from succinate dehydrogenase (SDH) of mammalian tissues in several ways. For example (a) FR requires NAD while SDH utilizes flavin nucleotide (FAD) as the coenzyme (b) FR acts only in one direction but SDH is a reversible enzyme (c) FR acts as the terminal electron acceptor under anaerobic conditions while SDH has no such property. Levamisole was shown to inhibit the FR in Ascaris [43]. 

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