Coenzyme Activity
Nicotinamide is the form in which the vitamin is found in its physiologically active combinations. Two well-defined coenzymes contain nicotinamide. These act with a large group of hydrogen-transport enzymes and arc discussed specifically. The first is diphosphopyridine nucleotide (DPN), coenzyme I (Co!), or NAD for nicotinamide adenine dinucleotide. It contains nicotinamide-ribose-phosphate-phosphate-ribose-adenine. Preiss and Handler consider the following reactions involved in the biosynthesis of DPN by enzymes in yeast, erythrocytes, or liver.
Nicotinic acid + 5-phosphoribosylpyrophosphate ---> nicotinic acid nucleotide + PP
Nicotinic acid nucleotide + ATP ---> desamido-DPN + PP
3. Desamido-DPN + glutamine + ATP + HP ---> DPN + glutamate + AMP + PP
It should be noticed that amide formation (-NH2 from glutamine) occurs following the completion of the dinucleotide structure. No enzyme capable of direct conversion of nicotinic acid to the amide has been found.
The other coenzyme containing niacin is triphosphopyridjne nucleotide (TPN), also called coenzyme II (Coll) or NADP for nicotinamide adenine dinucleotide phosphate. This is composed of nicotinamide-ribose-phosphate-phosphate-ribose-2' -phosphate adenine: It differs from DPN only in the presence of a third phosphate group on carbon 2 of the ribose attached to adenine. It is synthesized from DPN and ATP. The DPN kinase enzyme mediating the reaction was isolated from pigeon liver by Wang and others:
DPN + ATP MgH ---Mg--> TPN + ADP
The primary action of the two coenzymes is to remove hydrogen from substrates as part of dehydrogenase enzymes and transfer hydrogen and/or electrons to the next coenzyme in the chain or to another substrate which then becomes reduced. These enzymeS' are thus alternately oxidized and reduced. DPNH represents the reduced form. Many metabolic processes utilize one or other of these coenzymes. Discussion of the mechanism by which they operate can be found. The structure ofDPN and TPN are shown herewith: