Nicotinamide

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Introduction
Nicotinamide adenine dinucleotide(NAD) is
acoenzyme found in all livingcells. The compound
is a dinucleotide, because it consists of
twonucleotidesjoined through their phosphate
groups. One nucleotide contains anadeninebase
and the othernicotinamide. Nicotinamide adenine
dinucleotide exists in two forms, anoxidizedand
reducedform abbreviated
asNAD+andNADHrespectively.

NADH, short for nicotinamide adenine

dinucleotide, is an important pyridine
nucleotide that functions as an oxidative
cofactor in eukaryotic cells.
NADH plays a key role in the production of
energy through redox reactions.
NAD serves as a cofactor for
dehydrogenases, reductases and
hydroxylases, making it a major carrier of
H+and e- in major metabolic pathways
such as glycolic acid, fatty acid synthesis,
steroid synthesis.

Fig: Nicotinamide adenine dinucleoti

Concept
Involved in redox reactions
Takes part in cellular processes, DNA repair, signal transduction,
etc.
Also involved in de novo biosynthesis, slavage pathway
Used for discovery & development of novel treatments of
medical conditions like cancer, aging

 NAD is oxidized form and become reduced this forms NADH

which can be used as reducing agent to donate electrons.
At physiological PH NAD is singly charged anion while NADH is
doubly charged anion
In organisms, NAD is synthesized by de-novo pathway from
amino acids tryptophan or aspartic acid.
Alternately it can also be taken from food as vitamin known as
niacin

History

 In early 19th century over consumption of corn or corn meal caused a disease
Pellagra in Europe, U.S, Italy.
Dr. Joseph Goldberger of U.S Public Health Services demonstrated that
Pellagra was a dietary disease. In the late 1930s, studies by Dr. Tom Spies
and Clark Cooper established that niacin cured pellagra in humans.
Pellagra is a vitamin deficiency disease most frequently caused by a chronic
lack of niacin in the diet. Pellagra developed classically as a result of niacin
(vitamin B3) deficiency, tryptophan deficiency which resulted in decreased
NAD (nicotinamide adenine dinucleotide) production leading to most of the
pathology since NAD and its phosphorylated NADP form are cofactors
required in many body processes.
The human body converts tryptophan to nicotinic acid.
It was proven correct with the isolation of nicotinic acid which cured
pellagra.

 Niacin is involved metabolic reactions of FA, amino acids &

carbohydrates.
Niacin serves as a component of cosubtsrates NAD & NADP which
are key components of redox reactions & participate in many
cellular processes.
The body readily converts nicotinic acid to nicotinamide but a little
of it is stored as NAD n NADP in body.
Thus, niacin deficiency was produced in humans fed with corn meal
which consisted of low niacin & tryptophan levels.
Nicotinic acid & nicotinamide are major forms of niacin & exert
their physiological functions as precursors of nicotinamide adenine
dinucleotide (NAD).

Reactions
NAD + and NADP + play an essential role in many biochemical reactions, especially
redox reactions in which oxidoreductase enzymes transfer hydrogen
NAD + and NADP + act as electron acceptors in oxidoreductase catalyzed
reactions; NADH and NADPH act as electron donors.
Reactions catalyzed by Nucleotide containing enzymes:
1) The redox reaction shown in Figure below is catalyzed by the
oxidoreductase enzyme alcohol dehydrogenase.

Fig:Reduction of NAD to NADH

Mechanism: Hydride mechanism

2)Conversion of Imine of alpha-ketoglutrate to a-ketoglutrate.The reaction

is catalyzed by glutamate dehydrogenase.

3)Conversion of Glyceraldehyde-3-Phosphate to 1,3-Biphosphoglycerate

catalyzed by enzyme Glyceraldehyde-3-phosphate dehydrogenase.One
of the most important step in Glycolysis pathway.

4)Glucose-6-phosphate catalyzes oxidation of

aldehyde(hemiacetal),atC1of glucose-6-phophate,to a carboxylic
acid in ester linkage(lactone).NADP servers as electron
acceptor.This is a step involved in pentose phosphate pathway.

One electron mechanism

ADVANTAGES
Effectively treat acne by its anti inflammatory action and
reducing sebum.
Improve skin barrier function through decreasing water loss
through the epidermis,thus increasing skin hydration.
Reduce actinic keratoses and possibly reduce the risk of skin
cancer.
Extends replicative lifespan of human cells.

DISADVANTAGES
Avoided in patients with active peptic ulcer disease.
At high doses causes nausea, diarrhoa,bleeding, updet stomach.
Loss of appetite
Avoided in patients with severe hypotension.

APPLICATIO
N

 NAD+ is direct target of the drug isoniazid, which is used in the

treatment of tuberculosis, an infection caused by mycobacerium
tuberculosis.Isoniazid is a prodrug and once it has entered the bacteria,
it is activated by a peroxidase enzyme, which oxidizes the compound
into a free radical form, this radical then reacts with NADH, to
produce adducts that are very potent inhibitors of the enzymes enoylacyl carrier protein reductase and dihydrofolate reductase.
Nicotinamide, also known as niacinamide or nicotinic acid amide
active form of vitamin B3. It is essential for good health; deficiency
leads to a serious illness, pellagra. Oral nicotinamide can be used
effectively to treat pellagra.

 NADH stands for "nicotinamide adenine dinucleotide (NAD) +

hydrogen (H)." This chemical occurs naturally in the body and
plays a role in the chemical process that generates energy.
People use NADH supplements as medicine.
NADH is used for improving mental clarity, alertness,
concentration, and memory; as well as for treating Alzheimers
disease. Because of its role in energy production, NADH is also
used for improving athletic endurance and treating chronic
fatigue syndrome (CFS).