Overview of Niacin and Derived Cofactors

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(Last Updated On: April 23, 2017)
The structure of niacin and nicotinamide

The structure of niacin and nicotinamide

What is niacin?

Niacin is an organic acid the IUPAC name of which is pyrimidine-3-carboxylic acid. It is also called as nicotinic acid or vitamin B3. However, the biologically active form is nicotinamide, not the niacin which is formed during the formation of niacin-derived cofactors nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Niacin is one of the main essential nutrients of human beings and is taken through the food source and as a supplement.

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What is niacin used for and derived cofactors?

Niacin is the precursor of cofactors; NAD+ and NADP+. These cofactors are important for the metabolism of glucose, lipid, and lipid metabolism. These cofactors are also important for the synthesis of some of the important steroid hormones derived from cholesterol and cholesterol biosynthesis.

Niacin derived cofactors; NAD+ and NADP+ are one of the important cofactors required by oxidoreductase enzymes. these oxidoreductase enzymes catalyze redox reactions. These two cofactors are interconvertible. NAD+ is converted to the NADP+ catalyzed by NAD+ kinase while NADP+ is converted back to the NAD+ catalyzed by the NADP+ phosphorylase. They act as reducing agents in their hydrogenated (reduced) forms NADH and NADPH respectively.

Interconversion of NAD+ and NADP+

Interconversion of NAD+ and NADP+

They act on separate pathways and their roles are not interchangeable. NAD+/NADH are involved in the oxidative catabolic pathways such as glycolysis, TCA cycles, and amino acid catabolism while NADP+/NADPH are involved in the reductive biosynthetic pathways such as cholesterol biosynthesis, hormone biosynthesis, lipid biosynthesis, etc.

non-redox reaction catalyzed by NAD+ Dependent DNA ligase that ligates the nicked DNA.`

A non-redox reaction catalyzed by NAD+ Dependent DNA ligase that ligates the nicked DNA. Foster et al. 1980

However, some enzymes requiring aforementioned enzymes are not oxidoreductase and catalyze non-redox reactions such as DNA ligase participating in the ligation of two DNA fragments. DNA ligase is an important enzyme that plays an important role in the DNA repair. It joins the nicked DNA and helps the cell to repair damaged DNA.

Other non-redox reaction catalyzing enzymes  include ADP-ribosyltransferase that catalyzes the ADP-ribose transfer reaction in which ADP-ribose unit is added to the target protein during the posttranslational modification. Similarly, poly(ADP-ribose)polymerases that involve in the DNA repair and apoptosis also require NAD+ for their catalysis. 

Niacin is primarily used to the treatment of cholesterol. It promotes the increase of HDL cholesterols while lowers the LDL than any other prescribed medicines. Niacin inhibits the diacylglycerol acyltransferase-2 preventing Triacyl Glycerol (TAG) biosynthesis that leads to the decreased production of LDL. Niacin also inhibits the hepatocyte HDL catabolism receptor preventing the catabolism of HDL. This way, the blood level of HDL increases while LDL level decreases.

Sometimes it is prescribed to the lower the risk of heart  attack in the people with high cholesterol however peoples with allergic to this compound are not recommended to use niacin.

Niacin deficiency

It has been found that people with chronic alcoholism are deficient of niacin because alcohol is metabolized by two enzymes; alcohol dehydrogenase and aldehyde dehydrogenase. These enzymes are NAD-dependent and excessive expression of those enzymes requires an excess of niacin for the production of NAD+.

Niacin deficiency is a common problem seen in the people suffering from poverty and malnutrition. These people do also suffer from pandemic deficiency disease that means they are deficient of five different vitamins; niacin, vitamin C, thiamine, vitamin D and vitamin A. Niacin deficiency may lead to some health problems such as nausea, mouth and skin lesions, anemia and headache etc.

Side effect of niacin

Excess of niacin (more than a recommended dose) may cause severe liver damage and stomach ulcer. Other side effects of niacin include warmth, itching, redness and can be worse if taken after a hot beverage or alcoholic drinks.

Taking niacin along with medicines such as colestipol and cholestyramine is not recommended because these medicines might cause an adverse reaction. So, you have to take them at a different time, at least with an interval of 4 to 6 hours. Pregnant women are not recommended to use niacin to treat their high blood cholesterol level because niacin may harm unborn babies.

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