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Metabolism > B3 > Flashcards

B3 Flashcards

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)

A

soluble electron carriers that move readily from one enzyme to another

22
Q

Coenzymes for…

A

> 200 enzymes, primarily dehydrogenases

23
Q

Goes through the liver to make NAD+

A

nicotinic acid

24
Q

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

A

Nicotinamide

25
Q

One of the most important mechanisms…

A

Glycolysis… Glyceraldehyde 3-phosphate

26
Q

NAD+ and NADP+ function

A

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
Q

NAD+ serves as…

A

A hydrogen (electron) acceptor forming NADH, which donates electrons to electron transport chain.

28
Q

In the enzyme complex…

A

the reduced flavo (FADH2) protein is oxidized by NAD+ which then transfers reducing equivalents to the respiratory chain.

29
Q

Non-redox function of NAD

A

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
Q

ADP ribosylation

A

Catalzyzed by the enzymes: Mono ADP ribosyl transferase (1 ADP ribosyl) and Poly ADP ribosyl polymerase ( >200 ADP ribosyl groups)

31
Q

Poly ADP-ribose polymerases

A

Family of proteins involved in DNA repair, cell differentiation and apoptosis

32
Q

Poly (ADP-ribose) polymerase-1 (PARP-1)

A

Modifies nuclear proteins by poly ADP- ribosylation. Involved in DNA repair. Activated in response to UVB radiation.

33
Q

Impaired function of PARP-1

A

Contributes to the skin’s sensitivity to sun in pellagra

34
Q

Biosynthesis of Niacin

A

Nearly all animal species can synthesize niacin, NAD (H) and NADP(H) from tryptophan.

35
Q

Mg of tryptophan to produce 1 mg of niacin

A

60 mg

36
Q

Status Assessment

A

Urinary excretion of methyl nicotinamide.

37
Q

Deficiency

A

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
Q

Pellagra

A

Most severe nutritional deficiency in US history. Nearly 100,000 deaths between 1900-1940. Mostly in rural south, mainly blacks and women.

39
Q

What caused pellagra?

A

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
Q

Dermatological changes

A

most prominent in face, neck, back of hands and forearms. Skin cracking, desquamation, hyperkeratinosis.

41
Q

GI Lesions

A

Angular stomatitis, glossitis, achlorhydria

42
Q

Neurological symptoms

A

Anxiety, depression, fatigue

43
Q

Other

A

Anemia almost always observed in pellagra

44
Q

Short Term toxicity

A

vasodilation, burning sensation on skin, nausea, vomiting, diarrhea

45
Q

Long term toxicity

A

hyperpigmentation of skin, abnormal glucose tolerance, hyperuricemia, peptic ulcers, hepatomegaly, jaundice

46
Q

Toxicity

A

Methyl deficiency-methylation to form urinary metabolites- increased homocysteine… Larger doses ~10g/ day– liver damage

47
Q

Pharmacologic Uses (nicotinic acid)

A

used to treat hyperlipidemia (up to 6mg/ day)

48
Q

Mechanisms of lipid lowering

A

Inhibits lipolysis in adipose tissue. Decreases hepatic VLDL secretion and LDL production. Decreases hepatic triglyceride synthesis. Increases HDL concentration in blood.

49
Q

Study results

A

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
Q

How does vitamin B1 function in the pyruvate dehydrogenase complex?

A

Transfers a hydroxyethyl group

Metabolism (8 decks)

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