Niacin (B3)

Free form niacin form - 2 compound families

acid form (-COOH): nicotinic acid

amide form (-NH2): nicotinamide

how convert between acid free form and amide free form?

enzyme

NAD and NADP are most often positively charged - true or false?

TRUE - bc they are electron donors.

animal sources - what are best examples to get nicatinimide?

fish and meats. 

when you slaughter an animal, what happens to the niacin source?

still get niacin, but not getting the natural form found in the animal. Niacin gets broken down.hydrolyzed. 

richest plant sources

enriched gains.

processing of grains causes what to happen?

niacin break down

why are animal sources are preferred?

bc it has immediate use functions.

NAD and NADP with oxidized forms (NAD+ and NADP+)

niacin is also found bound to what?

carbodhydrates and small peptides

aside from dietary sources, niacin can be synthesized by the liver via amino acid what?

tryptophan

in the formation of niacin from tryptophan, how many rate limiting enzymes are there?

2 rate limiting enzymes.

similar to how thiazole in thiamin is the reactive site (reactive carbon), where is the reactive site for niacin?

nicotinamide (hydride ion)

compared to nicotinamide, how his NAD and NADP different?

A + D = adenosine and ribose

have non-coenzyme roles

NADP

NAD plus phosphate

what type of niacin found in animal & plants

animals - NAD or NADP structure

plants - nicotinic acid (free form)

what happens when NADP is ingested (especially present in animal forms)?

where is NADP hydrolyzed?

By what enzyme NADP hydrolyzed?

NADP is hydrolyzes within the intestine cells by the enzymes PYROPHOSPHATASE to NAD and glycohydrosylase to free nicotinamide.

two enzymes to bring all the way to nicotinamide. 

NADP to NAD

PYROphosphaTASE

NAD to free form nicotinamide.

glycohydroslyase

how is riboflavin similar to niacin in this manner?

riboflavin FAD → (FAD pyrophosphatase) to FMN, FMN (FMN phosphtaste) to free riboflavin

niacin NADP → (pyrophosphtase) to NAD, NAD to free by (glycohydrosylase)

very low absorption capacity starts to occur where?

the stomach

most of niacin absorption occurs WHERE?

small intestine

transporters in the small intestine - are they sodium dependent?

YES sodium dependent.

transport for niacin active or passive transport? require energy?

transporters are energy dependent (active transport). High concentration could be passive diffusion (3-4grams).

transport from the liver to all the tissues are convereted back to what?

coenzyme forms

NADP → NAD (what enzyme)

pyrophosphatase

NAD → nicotinamide (what enzyme)

glycohydrolase

in plasma, niacin is found in what form?

nicotinamide (some nicotinic acid)

primary precursor to convert to NAD and NADP

nicotinamide. 

nicotinic acid cannot covert into the two, so has to first convert to nicotinamide. 

liver is the major metabolic organ to convert nicotinic acid to nicotinamide. True or false.

true

Is the conversion between nicotinamide, NAD, and NADPH reversible?

Yes

Can the conversion between nicotinamide, NAD, and NADPH reversible happen in the tissues?

no, only possible in the LIVERRRR

do tissues have the conversion capacity to go from NADP/NAD to nicotinamide?

No!!!

WHAT has the conversion capacity to go from NADP/NAD to nicotinamide?

the LIVERRRR

what is the starting animo acid to create niacin?

tryptophan

how does the tryptophan pathway compare to serotonion synthesis and niacin?

serotonin synthesis - tryoptophan monooxygenase

niacin - tryptophan dioxygenase

NAD & NADP hydrolyzed?

nicotinamide free form.

nicotinic acid to nicotinimide exlusive ot what?

enzymes in the liver.

Tissues cannot efficiently convert nicotinic acid → nicotinamide.

what is the first rate limiting enzyme (tryptophan to niacin)

kynurenine MONOOXIGENASE

what COENZYME is required for kynurenine MONOOXIGENASE (first rate limiting step?)

riboflavin dependent

what is the second rate limiting step? That converts 3-OH kynurenine to 3-OH anthranilic acid. 

KynureninASE

what is the COENZYME in the second rate limiting step?

PLP/Vitamin B6

what are the two rate limiting enzymes?

kynurenine monooxigenase (riboflavin dependent) & kynureninase (PLP/B6 dependent)

nicotinic acid adeninie dinucleotide → nicotinamide adenine dincuelotide (NAD+)

NAD synthetase

what cobsubstrate is requied for NAD synthetase (amino acid)

glutamine (converts into glutamate) + ATP

NAD+ → NADP+

NAD kinase (addition of a phosphate) + ATP

every 60mg of tryptophan, how many mg of niacin produced?

1mg

niacin equivalent

based on protein intake

t or f nad and nadp function in oxidaion and reduction?

true

Both NAD and NADP are trapped intracellular with _____ being predominant form..

NAD

In liver cells, excessive niacin and tryptophan are converted to ______ and stored ________________. 

NAD; stored non-enzyme bound. 

NAD is predominant in the oxidized form of what in cells?

NAD+

NADP if found in cells is mainly found in the reduced form of what?

NADPH

What are the main functions of niacin?

• COENZYME ROLE

  • oxidation

  • reduction (new compounds synthesized)

  • folate metabolism (riboflavin, niacin, pantothenic acid)

• non CONEZYME

  • ADP-ribose (WITHOUT nicotinamide) - involved in PTM of proteins and formation of cyclic ADP ribose. 

Thiamin was involved with a lot of WHAT enzymes?

Decarboxylase & Hydroxylase enzymes

Niacin is similar to thiamin, because it also uses WHAT enzymes?

DEHYDROGENASES.

NAD and NADP act as an electron donor or hydrogen acceptor

How many chemical reactions do NAD and NADP participate in?

More than 200 chemical rxns

In oxidized forms, both NAD and NADP posses what charge?

positive

NAD is involved in what type of reactions?

OXIDATION rxns

what are some examples of oxidation reactions NAD is involved in? (5)

• oxidative decarboxylation of pyruvate (4 enzymes: niacin, riboflavin, thiamin, pathothenic acid)

• oxidation of acetyl-CoA - already in Krebs cycle, so getting utilized

• beta oxidation of fatty acids - similar to riboflavin acyl-CoA dehydrogenase (requires FAD) *****in thiamin and transketolase, in HMP shunt other than pentose sugar, made NADPH. NADPH role is synthesis of fatty acids*****

• oxidation of alcohol (alcohol dehydrogenase and acetylaldehyde dehydrogenase)

• vitamin B6 metabolism

NADPH and functions (8)

BIOSYNTHESIS ROLE

• FATTY ACID SYNTHESIS

• cholesterol synthesis

• steroid hormone synthesis - cyclic/aromatic compounds (come from cholesterol derived compounds - reproductive and non estrogen, corticosteroids, aldosterone, progesterone)

• DNA synthesis (thioredoxin - riboflavin FAD also plays a role)

• oxidation of glutamate (utilization of glutamate after glutamine is utilized as a cosubstrate to form NAD)

• dehydroascobrate to ascorbate (glutathione reductase is an NADPH dependent)

• nucleic acid synthesis (in combo with folate)

Nonredox/noncoenzyme role of Niacin.

Structure that is not nicotinamide. RIBOSE SUGAR AND ADENOSINE.

what part of the niacin structural functions in the non-redox/non-coenzyme role?

ADP-ribose (adenosine diphosphate ribose)

Which compound/coenzyme is the DONOR of ADP-ribose? Only ONE compound?

NAD

how is ADP ribose utilized (KNOW 2 WAYS)?

1. ribosylation

2. forming cyclic ADP

PTM

in Vitamin C - amidation was a form of PTM that allowed protein structures to undergo another change in shape of structure to make it more functional. How hormones and pepetides where produced. How aldosterone, oxytocin, growth homrone, CCK, etc were made. 

ribosylation

ADP-ribose from NAD → involved in ribosylation (example of a PTM)

used in cellular and molecular reactions. (DNA repair, replication, transcription, G protein activity, calcium signaling). 

ADP ribose when it is cyclic can act how?

second messageer system → carries enzyme activity such as movement and moibilzation of CALCIUM. 

How is niacin synthesized?

start - tryptophan

rate limiting T COFACTOR IN THIS PATHWAY!!

Metabolism & Exrected

niacin BREAKDOWNS.

NAD - can separate into ADP ribose

NAD hydrozyled

nictotinamide + ADPribose

what happens ot the nicotinamide?

it is methylated and oxidized in the liver into other metabolites.

MOst important structure metabolite of niacine?

N-methyl nicotinamide (can be measured in urine and give accurate of BODY STORES!!)

What are the two major metbaolites of niacin?

N-methyl-nicotinmide & N-methyl 2-pyridone carboxamide.

N-methyl-nicotinamde is correlated with ur9ine asseesment of body stores. 

What is the major excretion route for niacin?

URINE!!

What are food sources of niacin?

more animal based, but can also get form plant based.

chicken, turkey, and tuna best sources. 

RDA for niacin

16 NE for men

14 NE for woman

Deficiency of NIACIN

pellagra

what is another name of pellagra?

4Ds

what are the 4Ds

dematitis, dementia, diarrhea, and death.

which is the only dietary deficinecy disease to reach epidemic proprtions in the US?

NIACIN

Pharmacological benefits of niacin?

niacin considered a medicine. was used as a treatment for HIgh BP in 1970s and 1980s. 

large doses treated HYPERCHOLESTEROLEMIA (high blood cholesterol)

niacin is a hepatoxin at high doses?

Yes hepatoxin. canot take too much.

potent vasodilator - rush blood AWAY form HEART.

Above 1 gram toxic effects.

statins combine with niacin (modified form)

modified form does not have vasodilator effects. fake one that does not have flushing of skin, itching, nauserea, or liver damage.

How to assess NIACIN?

N-methyl nicotinamide in URINE (not just once, 24-48 hours, creatitine levels kidney function normal)

RBC cells to see NAD concentration OR NADP:NADP ratio in RBC