lecture 10: niacin

Question 1

pellagra

Answer 1

niacin deficiency
melancholia, crusty skin, weakness

Question 2

niacin (vitamin B3) is a precursor to…

Answer 2

NAD - coenzyme for hundreds of redox reactions, substrate in DNA repair rxns, etc

3 forms of B3 (all from diet) that are converted to NAD

Question 3

niacin and schizophrenia

Answer 3

theorized schizophrenics might have a genetic disorder requiring greater dietary niacin, experiments revealed therapeutic effect of niacin supplementation
only helps with certain subset

Question 4

Why might niacin supplementation help with a subset of schizophrenia? What type of genetic disorder may be the cause?

Answer 4

if it is a disorder for decreased affinity of niacin, increased concentration can offset these effects
not all schizophrenia is caused by increased Km/decreased affinity for niacin

Question 5

associated risk factors of pellagra

Answer 5

poverty and corn consumption

poverty: staple foods are not nutritious, all calories/diet from one food

Question 6

redox reaction and niacin

Answer 6

NADH and NADPH are used as coenzymes for many reactions, often as proton/electron acceptor/donor

generally NAD(H) in catabolic, NADP(H) in anabolic

Question 7

4 classes of enzymes play dominant roles in controlling NAD levels

Answer 7

PARP, Sirtuin, CD38, IDO

first 3 use NAD as a substrate, produce nicotinamide as a side product, which is recycled back to NAD via salvage pathway

Question 8

PARP

Answer 8

PARP uses NAD as substrate to generate polyADP ribose for DNA repair

PARP activation directly proportional to degree of DNA damage

roles in arrest of cell division, DNA repair

Question 9

sirtuins

Answer 9

NAD dependent acetylases
use NAD as substrate to couple lysine deacetylation to NAD hydrolysis

Question 10

CD38

Answer 10

NAD as substrate to generate activators of intracellular calcium release, surface of immune cells

CD38-deficient mice have persistant elevated NAD levels

Question 11

NAD salvage and NAD de novo pathway

Answer 11

NAD salvage pathway: nicotinamide and nicotinamide riboside
de novo: nicotinic acid (niacin)

nicotinamide and nicotinic acid require addition of phosphoribose and AMP

nicotinamide ribose becomes phosphorylated, then bound to AMP

Question 12

IDO

Answer 12

uses tryptophan as a substrate, catalyzes first step in de novo synthesis of NAD

Question 13

niacin and heart health

Answer 13

nicotonic acid form can result in lipid metabolism and therefore benefits for heart disease

Question 14

What are the two general roles of niacin-derived NAD(H)? By which mechanisms are they recycled within the cell for continued use in metabolic processes?

Answer 14

1) coenzyme for redox reactions
2) substrate in reactions for DNA repair, transcriptional regulation
recycled via NAD de novo and NAD salvage pathways