Metabolic functions of niacin in the human body and role in health

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+
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. NAD in redox reactions
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

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
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 16, 2018 13