1. Metabolic functions of niacin
Domina Petric, MD

2. Coenzyme functions
Niacin functions metabolically as the essential component of the enzyme co-substrates NAD(H) and NADP(H).
The most central electron transport carriers of cells, each acts as an intermediate in most of the hydrogen transfers in metabolism, including more than 200 reactions in the metabolism of carbohydrates, fatty acids and amino acids according to the general reaction:
substrate + NAD(P)+ → product + NAD(P)H + H+
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

3. Coenzyme functions
The hydrogen transport by the pyridine nucleotides is accomplished by two-electron transfers in which the hydride ion (H-) serves as a carrier for both electrons.
The transfer is stereospecific, involving C-4 of the pyridine ring.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

4. Coenzyme functions
The two hydrogen atoms at C-4 of NAD(H) and NADP(H) are not equivalent.
Each is stereospecifically transferred by the enzymes to the corresponding substrates.
Stereospecificity is independent of the nature of the substrate and the source of the enzyme.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5. Coenzyme functions
The reactions catalyzed by the pyridine nucleotide dependent dehydrogenases occur by:
abstraction of the proton from the alcoholic hydroxyl group of the donor substrate
transfer of hydride ion from the same carbon atom to the C-4 of NAm
In many cases, this reaction is coupled to a further reaction, such as phosphorylation or decarboxylation.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

6. Metabolic roles
Despite their similarities of mechanism and structure, NAD(H) and NADP(H) have quite different metabolic roles and most dehydrogenases have specificity for one or the other.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

7. NAD in redox reactions
The oxidized form NAD+ serves as a hydrogen acceptor at the C-4 position of the pyridine ring, forming NAD(H) which, in turn, functions as a hydrogen donor to the mitochondrial respiratory chain (TCA cycle) for ATP production.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

8. NAD in redox reactions Glycolytic reactions
Oxidative decarboxylations of pyruvate
Oxidation of acetate in the TCA cycle
Oxidation of ethanol
ß-oxidation of fatty acids
Other cellular oxidations
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

9. NADP(H) in reduction reactions
The phosphorylation of NAD+ facilitates the separation of oxidation and reduction pathways of niacin cofactors by allowing NADP(H) to serve as a co-dehydrogenase in the oxidation of physiological fuels.
NADP(H) is maintained in the reduced state, NADPH by the pentose phosphate pathway such that reduction reactions are favored.
Many of these also involve flavoproteins.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

10. NADP(H) in reduction reactions
These reactions involve reductive biosyntheses, such as those of fatty acids and steroids.
NADPH also serves as a co-dehydrogenase for the oxidation of glucose 6-phosphate in the pentose phosphate pathway.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. Genomic stability
The niacin metabolite NAD(H) functions in the post-translational modification of nuclear proteins by poly(ADP-ribose) polymerase.
This enzyme uses NAD+ as a direct substrate to provide the ribosyl moiety that is added to the receptor protein.
Poly-ADP-ribosylated proteins function in signal transduction by modulating the activities of G protein and p53: role in DNA repair and replication, in cell differentiation and apoptosis.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

12. Glucose tolerance factor
Niacin has been identified as part of the chromium containing glucose tolerance factor of yeast, which enhances the response to insulin.
It is possible that this activity involves a metal-chelating capacity of nicotinic acid such as has been reported for zinc and iron.
November 22, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13. Literature
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc
November 22, 2018