Question

NAD+ & NADP+ are derived from which vitamin? Briefly describe their metabolic roles and account for the fact that they are only required in very small quantities (~20mg) within our diet.

Answer 1

Niacin or Nicotinic acid or vitamin b3 is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position.

Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters. The terms niacin, nicotinamide, and vitamin B3 are often used interchangeably to refer to any member of this family of compounds, since they have the same biochemical activity.

Food Sources

Endogenous synthesis

The liver can synthesize niacin from the essential amino acid tryptophan, requiring 60 mg of tryptophan to make one mg of niacin.

The actual daily requirement of vitamin B3 (niacin) depends on the quantity of the amino acid ‘tryptophan’ in the diet and the efficiency of tryptophan to niacin conversion. The conversion factor is 60 mg tryptophan to 1 mg niacin, which is referred to as 1 niacin equivalent (NE). This conversion factor is used for calculating both dietary contributions from tryptophan and recommended allowances of niacin.

However it's dietary requirements should be less than 20mg.

Niacin Functions

It is the precursor of NAD , NADP.

NAD and NADP roles

NAD:

NAD has various essential roles in metabolism:
1. Cofactor in redox reactions
2. Donor of ADP-ribose moieties in ADP-ribosylation reactions
3. Precursor of the second messenger molecule cyclic ADP-ribose
4. As Adenine Dinucleotide, it has important extracellular roles.

These roles are involved in energy metabolism, mitochondrial functions, calcium homeostasis, generation of oxidative stress, gene expression, immunological functions, aging, and cell death.

NAD is also related to bone marrow's health and cancer progression , and has a benefical role in preventing neurological degeneration.

NAD and Niacin deficiency induce the enzyme Nicotinamide-N-Methyltransferase. High activity of this enzyme is related to Parkinson's Disease and cancer.

NAD, and mostly NAM (Nicotinamide), have a particular role in regulation of mesenchimal stem cells. NAM is converted in NAD by the enzyme Nicotinamide phosphoribosyltransferase (Nampt). The activity of this enzyme determines the NAD/NAM ratio.
A good NAD supply increases bone mineralization and stimulates osteocyte proliferation.
A bad NAD supply, represented by an high concentration of NAM, induces adipocyte proliferation and blocks osteocyte growth, potentially leading to osteoporosis.

A NAD deficiency can then cause:
1. Deceleration of glycoliosis, Kreb's cycle and most of all electron transport chain
2. An increased susceptibility to ROS damage
3. Bone marrow and brain sufference
4. An increased adipocyte proliferation
5. An increased risk of osteoporosis.

NADP:

NADP has various roles in metabolism:
1. Coenzyme in anabolic reactions
2. Regenerator of reduced glutathione (GSH)
3. Source of reducing equivalents for Cytocrome P450 hydroxilations

NADP deficiency leads to higher sensibility to oxydative damage and higher sensibility to the toxic substrates of Cytocrome P450 (about 75% of drugs, ethanol).