Niacinussy

Question 1

Active form

Answer 1

Pyridine nucleotide coenzymes - NAD and NADP

Active site at double bond on top (allows H+ transfer)

Question 2

Main role of Niacin

Answer 2

NAD and NADP donate or accept H+

Involved in oxidation/reduction reactions

Question 3

Metabolic role

Answer 3

Catabolism of glucose, fatty acids, ketones (alcohols to ketones), amino acids (to keto acids)

Question 4

What types of reactions are NAD and NADP involved in?

Answer 4

NAD - catabolic (ketone oxidation, catabolism of AA, etc.)
NADP - biosynthetic (anabolic - PPP, fat and steroid synthesis HMG-CoA reductase, synthesis of glutamate and deoxyribonucleotides)

Question 5

4 B vitamins involved in pyruvate dehydrogenase:

Answer 5

• Thiamin
• Riboflavin
• Niacin
• Pantothenic acid (B3)

Question 6

What carbohydrate metabolism reactions are niacin involved in?

Answer 6

• TCA cycle
• Pyruvate dehydrogenase
• ETC

Question 7

Non-cofactor role

Answer 7

Serves as a substrate in ADP-ribosylation
- ADP-ribose part of NAD is transferred to acceptor protein and releases free nicotinamide
- involved in cell signalling: calcium mobilization – protein modifications: gene silencing, bacterial toxins, DNA damage and repair

Reduction of cholesterol and TG
- Pharmalogical doses of NICOTINIC ACID (not nicotinamide) of up to 6g/d
- Anti-lipolytic effect - triggers HSL, reducing VLDL and LDL
- Causes “flushing” - histamine, prostaglandins, vasodilation

Question 8

De-novo synthesis of niacin

Answer 8

Synthesized from oxidatively cleaving tryptophan
- 60mg Trp = 1mg niacin
- NE: niacin + 1/60
- Normal intake of Trp adequate to meet niacin req

Question 9

What nutrients are required in the conversion of Trp to Nicotinic acid?

Answer 9

Vitamin C, Riboflavin, B6. B6 is also required for oxidation to kynurenate.

Question 10

Niacin absorption

Answer 10

• Coenzyme (NAD) hydrolyzed to nicotinamide (NMN) in intestinal lumen
• Absorved in SI by facilitated and passive diffusion
• Nicotinic acid also absorbed in stomach via passive diffusion
• Cell trapping to NAD/NADP

Question 11

Transport of niacin

Answer 11

Goes to liver where converted to NAD. Surplus NAD hydrolyzed and circulated in plasma as unbound acid and amide forms; enters tissues via facilitated and passive diffusion; metabolic trapping/formation of nucleotides.

Question 12

Storage

Answer 12

Trapped as NAD/NADP in tissues; most in cytoplasm bound to PRO

Question 13

Excretion

Answer 13

Little lost in urine; reabsorbed via Na-dependent mech.; excess niacin converted to methylated derivatives in liver and excreted in urine
- Continuous turnover and little storage

Question 14

Food sources

Answer 14

High protein foods (Trp): meat, poultry, fish, legumes, nuts, some cereals, enriched grain products, dairy, eggs
- present as trigonelline in some foods

Question 15

Bioavailability

Answer 15

Usually unavailable from cereals (bran) - present as nicotinic acid bound to complex CHO and PRO; milling removes bran/germ.

Question 16

Requirements

Answer 16

• NE - 7mg NE/1000kcal (minimum 14mg/day)
• Male - 16; Female: 14; more in pregnancy and lactation
• UL = 35mg/day causing liver damage; seen at >100mg/day

Question 17

Determination of status

Answer 17

• Whole blood NAD/NADP
• breakdown metabolites in urine

Question 18

Deficiency - form, who’s at risk, signs

Answer 18

• Pellegra: assoc. with corn/sorghum based diets (most niacin unavailable and Trp is low) - alkaline substances like limewater/woodash liverates nicotinic acid (corn can be soaked in limewater to prevent deficiency in these diets)
• At risk: poor diet and inc energy req, drugs, alcoholism, cancer, genetic disorders (Hartnup’s Trp transporter deficiency)
• 3 Ds: dermatitis, diarrhea, dementia – skin: Casal’s collar, lesions, cracking, hyperpigmentation – GI: impaired absorption, anorexia, indigestion – Nervous system: tremor, anxiety, depression