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B3 Flashcards

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1
Q

First produced

A

From the oxidation of nicotine, isolated from the tobacco plant Nicotiana tabacum

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2
Q

Funk

A

Isolates nicotinic acid from yeast; suggests that it is related to vitamins B1 and B3

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3
Q

Goldberger

A

Demonstrates that pellagra is a dietary deficiency disease.

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4
Q

Elvehjem

A

Isolates substance from liver called “pellagra preventing factor”; identifies it as nicotinic acid

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5
Q

Spies

A

Cures human pellagra using nicotinamide

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6
Q

Renamed

A

Niacin (NIcotinic ACid + vitamIN)

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7
Q

Nicotinic acid

A

Contains COOH

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8
Q

Nicotinamide

A

CONH2

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9
Q

Nicotine

A

another nitrogen base

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10
Q

Food Sources

A

Meat, lima beans, lentils, pasta, cereal

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11
Q

Niacin food forms

A

Nicotinic acid and nicotinamide

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12
Q

Nicotinic acid food form

A

usual form in plants (protein-bound form)

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13
Q

Nicotinamide food form

A

usual form in animal tissue (from NAD(H), NADP(H))

usual form in supplements (as niacinamide)

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14
Q

Pharmacological dose absorption

A

Passive diffusion

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15
Q

Low concentration absorption

A

Appears to be a high-affinity acidic ph-dependent, carried-mediated mechanism, but not yet identified.

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16
Q

Main circulating form

A

Nicotinic acid and nicotinamide. Free form. Also bound to immunoglobulins IgA, IgG, IgM.

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17
Q

Tissue uptake

A

taken up by most tissues by passive diffusion

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18
Q

Cell/ tissues that use transporters

A

Erythocytes, kidney, brain.

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19
Q

Excreted

A

In urine. 1-mthylnicotinamide and free NAM

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20
Q

Functions

A

Metabolically as the essential component of coenzymes nicotinamide adenine dinucleotide NAD(H) and NADP(H)

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21
Q

NAD(H) and NADP(H)

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A

soluble electron carriers that move readily from one enzyme to another

22
Q

Coenzymes for…

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A

> 200 enzymes, primarily dehydrogenases

23
Q

Goes through the liver to make NAD+

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A

nicotinic acid

24
Q

Does not have to go through the liver to make NAD+

25
One of the most important mechanisms...
Glycolysis... Glyceraldehyde 3-phosphate
26
NAD+ and NADP+ function
serve as the most central electron carriers of cells, acting as intermediates in >200 reactions in metabolism.... Glycolytic reactions, oxidative decarboxylation of pyruvate, oxidation of acetate in TCA cycle, oxidation of ethanol, beta-oxidation of fatty acids.
27
NAD+ serves as...
A hydrogen (electron) acceptor forming NADH, which donates electrons to electron transport chain.
28
In the enzyme complex...
the reduced flavo (FADH2) protein is oxidized by NAD+ which then transfers reducing equivalents to the respiratory chain.
29
Non-redox function of NAD
Serves as a substrate for ADP ribosylation, a type of post-translational modification that adds an ADP ribosyl group to enzymes, modulating their activity
30
ADP ribosylation
Catalzyzed by the enzymes: Mono ADP ribosyl transferase (1 ADP ribosyl) and Poly ADP ribosyl polymerase ( >200 ADP ribosyl groups)
31
Poly ADP-ribose polymerases
Family of proteins involved in DNA repair, cell differentiation and apoptosis
32
Poly (ADP-ribose) polymerase-1 (PARP-1)
Modifies nuclear proteins by poly ADP- ribosylation. Involved in DNA repair. Activated in response to UVB radiation.
33
Impaired function of PARP-1
Contributes to the skin's sensitivity to sun in pellagra
34
Biosynthesis of Niacin
Nearly all animal species can synthesize niacin, NAD (H) and NADP(H) from tryptophan.
35
Mg of tryptophan to produce 1 mg of niacin
60 mg
36
Status Assessment
Urinary excretion of methyl nicotinamide.
37
Deficiency
Pellagra (Italian, "rough skin"). Pellagra was endemic in US in early 1900s. Rare in US today. Seen in malnourished (alcoholics, poor, elderly). Pellagra still observed in developing countries with a dependence on corn.
38
Pellagra
Most severe nutritional deficiency in US history. Nearly 100,000 deaths between 1900-1940. Mostly in rural south, mainly blacks and women.
39
What caused pellagra?
Infectious disease or dietary deficiency? Dr. Joseph Goldberger sent to investigate... occurred where corn was dominant crop. 1915 Goldberger induces pellagra in prisoners by feeding them a corn-only diet. Corn is a poor source of niacin, as well as tryptophan.
40
Dermatological changes
most prominent in face, neck, back of hands and forearms. Skin cracking, desquamation, hyperkeratinosis.
41
GI Lesions
Angular stomatitis, glossitis, achlorhydria
42
Neurological symptoms
Anxiety, depression, fatigue
43
Other
Anemia almost always observed in pellagra
44
Short Term toxicity
vasodilation, burning sensation on skin, nausea, vomiting, diarrhea
45
Long term toxicity
hyperpigmentation of skin, abnormal glucose tolerance, hyperuricemia, peptic ulcers, hepatomegaly, jaundice
46
Toxicity
Methyl deficiency-methylation to form urinary metabolites- increased homocysteine... Larger doses ~10g/ day-- liver damage
47
Pharmacologic Uses (nicotinic acid)
used to treat hyperlipidemia (up to 6mg/ day)
48
Mechanisms of lipid lowering
Inhibits lipolysis in adipose tissue. Decreases hepatic VLDL secretion and LDL production. Decreases hepatic triglyceride synthesis. Increases HDL concentration in blood.
49
Study results
3214 total subjects (1718 received niacin; 1696 placebo).... At 2 years, Niacin significantly: Increased HDL (35 to 42 mg/ dL), decreased LDL (74 to 62 mg/ dL), and decreased triglyceride (164 to 122 mg/dL)
50
How does vitamin B1 function in the pyruvate dehydrogenase complex?
Transfers a hydroxyethyl group

Metabolism (8 decks)

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