Niacin (4 questions) Flashcards
What are the oxidized forms of niacin?
NAD/NADP
What are the reduced forms of niacin?
NADH/NADPH
The term niacin is a generic term for?
Nicotinic acid and Nicotinamide
(T/F) The adequate intake for infants is based solely on niacin intake, because from birth to 6 months, the tryptophan that is going to be consumed by an infant is going to be used strictly for protein synthesis. They will not be converting tryptophan to niacin, as we see in older children and adults.
TRUE
How is NE defined?
NE = niacin equivalents.
FNB defines 1 NB as 1 mg niacin or 60 mg of the AA tryptophan (secondary source, which the body can convert to niacin)
What are food sources of niacin?
- Beef liver
- Chicken breast
- Marinara sauce
- Turkey
- Salmon
- Tuna
…fortified breakfast cereals, pasta
Poultry, beef, and fish provide XXXX mg niacin per serving, primarily in what form?
5-10 mg niacin
in the highly bioavailable forms of NAD and NADP
Plant-based foods, such as nuts, legumes, and grains provide XXX mg niacin per serving, in what form?
2-5 mg niacin, mainly as nicotinic acid
In some grain products, naturally present niacin is largely bound to polysaccharides and glycopeptides which makes it only about X% bioavailable.
30%
What form of niacin is provided in fortified foods?
NICOTINAMIDE; therefore, highly bioavailable bc its the free form
What organ can synthesize niacin from tryptophan?
The liver
How much tryptophan is converted to niacin?
~3%
60 mg of tryptophan yields 1 mg of niacin
What is Hartnup disease?
Autosomal recessive; individuals have defects in their ability to convert tryptophan to niacin; shown to have niacin deficiencies
How is niacin absorbed?
Once in nicotinamide form, it can be absorbed in the S.I. via sodium-dependent carrier-mediated diffusion
For pharmacological doses, it is absorbed by passive diffusion
In the colon, some can be absorbed via sodium-independent, high affinity carrier
How is niacin transported in the blood?
Majority is free niacin form
15-30% is bound to proteins
How does nicotinamide/nicotinic acid move across cell membranes?
Simple diffusion
EXCEPT for kidney tubules and RBCs require carrier transport; Brain uptake requires ATP
Where is the majority of excess niacin stored?
In the liver, excess tryptophan is converted to niacin and then to NAD, and very limited amounts are stored here.
Over 200 enzymes, primarily XXXX, require the coenzymes NAD and NADP.
Dehydrogenases
Act as hydrogen donors or electron acceptors, and enable nutrient metabolism and energy production
What is the major role of NADH?
NADH = Reduced form of NAD
To transfer its electrons from metabolic intermediates through the ETC to produce ATP; at Complex I
What is the major role for NADPH?
NADPH acts as a reducing agent in many biosynthetic pathways
—–Pentose Phosphate Pathway
—–Mito membrane malate aspartate shuttle
What are 3 nonredox activities of NAD derivatives?
- DNA repair of strand breaks
- Acts as second messengers involved in control of mobilization of calcium from intracellular stores, especially in neurons (one-way cells communicate via calcium-flux in and out of the cell)
- SIRTUINS (enzyme deactylases), catalyze the removal of acetyl groups from the target proteins containing actylated lysine residues
Explain how SIRTUINS affect the function of many enzymes. What are some of the functions affected?
Sirtuins (enzyme deactylases) catalyze the removal of acteyl groups from proteins. Typically, these proteins are actylated on lysine residues. The removal of the acetyled lysine residues is going to affect numerous functions of many enzymes including:
—enzyme activity
—cell signaling
—gene expression (DNA deacetylation)
What role does NADH have in the ETC?
NADH acts as a vehicle for getting electrons to the ETC; donated electrons at complex I
What happens once NADH drops off it’s electrons at XXXXXX?
Complex I.
The electrons will be passed from complex I and enter the intermembrane, this energy is going to pump 4 protons into the intermembrane space; and again in complex III; and 2 protons are pumped in Complex IV.
The pumping of protons in the ETC, generates….?
IONIC GRADIENT; which will power the enzymes that is embedded in the membrane, allowing it to make ATP from ADP + phosphate.
What enzyme is embedded in the membrane of the ETC? What is its function?
ATP synthase; takes protons generated from ETC, and generates ATP from ADP + phosphate
What is glutathione? Which form is the active form?
An endogenous antioxidant; important in terms of neutralizing pro-oxidic compounds, such as hydrogen peroxide.
The reduced form is the active form that is able to act as an antioxidant
What needs to happen so glutathione can carry out its functions?
NADPH will donate it’s electrons to RIBOFLAVIN (FAD —> FADH), then those electrons will be passed to glutathione. This will convert the oxidized form of glutathione to the reduced (active) form.
What enzyme does glutathione use for neutralizing pro-oxidants?
Glutathione peroxidase enzyme
For folate metabolism, NADP/NADPH is required for which 5 reactions?
- 5, 10-methylene THF —-> 5-methyl THF
- 5, 10-methenyl THF —-> 5, 10-methylene THF
- 10-formyl THF —-> THF
- THF —-> DHF
- Folic acid —–> DHF
What form of niacin has been used to treat hyperlipidemia?
NICOTINIC ACID; large doses up to 6g/day in divided doses has been shown to:
—lower total cholesterol
—lower LDLs
—increase HDLs
—reduce lipoprotein A concentrations
(T/F) Nicotinamide in large doses also reduces blood lipids.
FALSE; only nicotinic acid form
What form of niacin (in large doses) can be used topically to reduce inflammation associated with acne vulgaris?
NICOTINAMIDE
What dose of nicotinamide can reduce the rates of new nonmelanoma skin cancers and actinic keratosis?
500 mg doses BID
Niacin Deficiency
Pellagra, is characterized by the 4 D’s:
D: Dermatitis (similar to sunburn; hyperpigmented and scaly; changes in oral cavities)
D: Diarrhea (can lead to a reduced absorption of other nutrients)
D: Dementia
D: Death
What is the treatment for niacin deficiency?
Treatment requires oral intakes of ~300 mg of NICOTINAMIDE daily (usually divided into 3 doses), for about 1 month
What is the upper tolerable limit of niacin?
35 mg/day in adults for the general population
Toxicity presents as flushing of the skin
How is niacin status assessed, in clinical settings?
Urinary excretion of methyl nicotinamide (~0.8 mg/day)
2-pyridone in plasma
