Niacin Flashcards
properties of niacin
- White crystal
- Water & alcohol soluble
- has a few different molecules which can all be consumed
What is the vitamin form of niacin?
nicotinamide
What is the active form niacin
pyridine nucleotide coenzymes
* NAD = nicotinamide adenine dinucleotide
* NADP = nicotinamide adenine dinucleotide phosphate (phosphate replaces one of the hydroxyls on the ribose)
Mode of action for NAD(H) and NADP(H)
acts as a co-factor for dehydrogenases in accepting and donating H+
* NAD and NADP are similar in mechanism of action, but different metabolic roles and most dehydrogenases are specific for one or the other
metabolic role of niacin
NAD/NADPfunctioninhundredsofoxidoreductase systems ( with H-transfer)
* Act as H-acceptors in oxidation and H-donors in reduction reactions
* catabolism of glucose, fatty acids, ketones, amino acids (Alcohols to aldehydes/ketones, aldehydes to acids, amino acids to keto acids)
metabolic role of NAD-dependant enzymes
involved in catabolic reactions
* e.g. β-oxidation of fatty acyl CoA’s, oxidation of ketones, degradation of CHO, catabolism of amino acids, ETC
metabolic role of NADP-dependent systems
involved in biosynthetic reactions
* e.g. pentose phosphate pathway, synthesis of fats & steroids (HMG-CoA reductase), synthesis of glutamate & deoxyribonucleotides
Niacin role in PDH
As NAD+ it accepts 2 H+ from the FADH2 to become NADH+H and carries the H+ to the ETC
* oxidizes FADH2 to FAD
NAD(H) role in the CAC
Accepts H+ from substrates in multiple steps of the CAC and carries H+ to ETC necessary for energy metabolism
* PDH
* IDH
* 𝝰-KGDH
* MDH
NAD(H) role in ETC
contribute to intracellular respiratory mechanisms in all cells
* NADH+H is reduced at complex I and the H+ are pumped through the
niacin role in fat synthesis
Anabolic reactions require NADP(H)
* involved in the synthesis of cholesterol, TAG, PL, SFA, MUFA
niacin role in redox status regulation
NADPH+H is required for glutathione reductase whereby it donates the H+ to FAD and becomes NAD+. The FADH2 can then reduce GSSG back to GSH
niacin non-cofactor roles
- ADP-ribosylation
- Reduction of cholesterol & TG
niacin role in ADP-ribosylation
NAD serves as substrate not coenzyme
* The ADP-ribose moiety of NAD is transferred to an acceptor protein & releases free nicotinamide
* Binding of ATP-ribose to protein changes the function of the protein
* The transfers are important for cell signalling and protein modifications
niacin role in reducing cholesterol & TG
nicotinic acid consumed in large pharmacological doses (up to 6g/d) has been shown to dramatically reduce lipids in plasma. It can bind a receptor on white adipose tissue and regulate hormone sensitive lipase.
* Only nicotinic acid can bind it, NOT nicotinamide
* Not widely used because this receptor is also on macrophages and other cells similar so get release of inflammation effect
* “flushing” = histamine, prostaglandins, vasodilation
de novo synthesis of niacin
Synthesized from tryptophan
* Trp is oxidatively cleaved
* Need 60 mg Trp to produce 1 mg niacin
* NE (niacin equivalents): preformed niacin + 1/60 Trp
* normal intakes of Trp adequate to meet niacin requirements without need for preformed niacin
What other nutrients are required for niacin synthesis?
conversion of Trp to nicotinic acid, NAD etc. require vitamin C, riboflavin and vit6
* deficiency in one of these can result in functional deficiency of niacin
absorption of niacin
- Usually dietary niacin is in NAD form so it is hydrolyzed to nicotinamide in intestinal lumen
- absorbed in SI by facilitated and passive diffusion
- nicotinic acid can also be absorbed in stomach by passive diffusion
- once inside cell metabolized to NAD(P) (metabolic trapping) or absorbed into portal vein
How is NAD+ hydrolyzed to nicotinamide?
NAD
↓ pyrophosphatase
nicotinamide mononucleotide (NMN)
↓ alkaline phosphatase
nicotinamide ribose
↓ glycohydrolase
nicotinamide
transport of niacin
- goes to liver first = converted to NAD
- surplus NAD hydrolyzed and released into circulation
- circulates in plasma as unbound forms of acid & amide
- enters peripheral tissues by facilitated & passive diffusion
- formation & metabolic trapping of nucleotides
Storage of niacin
- niacin gets trapped in tissues by conversion to NAD & NADP
- most stored in cytoplasm bound to protein
- some in circulation
continuous turnover & little storage
excretion of niacin
- little loss of niacin in urine with modest intake
- reabsorbed by active Na-dependent mechanism
- excess niacin converted in liver to methylated derivatives and excreted in urine
continuous turnover & little storage
Food sources of preformed niacin
- meat, poultry, fish
- legumes, peanuts
- some cereals, enriched grain products
- dairy, eggs (Trp)
Good food sources of trp
eggs
other sources of niacin
- Some foods have niacin present as trigonelline which is a methylated niacin form and if removed get the niacin
- in coffee, nicotinic acid is liberated by roasting
bioavailability of niacin in grain products
most niacin in cereals (in bran) not available
* present as nicotinic acid bound to complex CHO & proteins
* milling removes bran/germ
How are Niacin DRIs measured?
measured in Niacin Equivalents which takes into account the niacin and tryptophan that is in food
What are the niacin DRIs?
7 mg NE/1000 kcal and minimum 14 mg/day
* RDA M=16 mg/d & F=14 mg/d
* increases with pregnancy and lactation
niacin UL
UL = 35 mg/day with long-term intake
* risk of liver damage
* effects seen at >100mg/day nicotinic acid
determination of niacin status
- whole blood NAD/NADP (good measure of status)
- can look at Tryptophan, Pyridoxine, or Leucine (indirect measures)
- Breakdown metabolites in urine
Main disease of niacin deficiency
pellagra
* multi-factorial dietary deficiency
What is pellagra associated with?
associated with corn & sorghum based diets where most niacin is unavailable & Trp content low
What can be done liberate niacin in corn based diets?
using alkaline substance (limewater or wood ash) liberates nicotinic acid
* Central America = cooking in lime & consumption of coffee
Who is at risk for niacin deficiency?
- poor diet & ↑ energy requirements
- certain drugs
- alcoholism
- cancer
- genetic disorders = Hartnup’s (Trp transporter deficiency)
3 Ds of niacin deficiency
dermatitis: skin = Casal’s collar; lesions, cracking, hyperpigmentation
diarrhea: GI = impaired absorption; anorexia, indigestion
dementia: nervous system = tremor; anxiety, depression
