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Nutrition and Metabolism > Exam 1 Material > Flashcards

Exam 1 Material Flashcards

1
Q

Paul Gyorgy

A

identifies factor that cured dermititis in rats, B6, in 1934

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2
Q

R protein

A

haptocorrin or transcobalamin 1, glycoproteins secreted by salivary glands, binds to b12 (in stomach) and protects it from stomach acid

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3
Q

Intrinsic factor

A

IF, glycoproteins secreted by gastric parietal cells (stomach), binds to b12 in intestine (duodenum) and transports it to IF receptor (in ileum)

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4
Q

Transcobalamin 2

A

main transport protein for B12 in PLASMA, binds to B12 in portal bloodstream, less common than TCB1

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5
Q

Folate

A

natural form, reduced form, polyglutamate form, can be 5-methyTHF or 10-formylTHF, some synthesized in bacteria in gut

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6
Q

Folic Acid

A

synthetic form, oxidized form, monoglutamate form, most found in enriched cereals and supplements (also grains)

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7
Q

Glutamate carboxypeptidase 2 (GCPII)

A

cleaves glutamates off of food folate in jejunal brush border, exopeptidase (cleaves terminally), optimum pH 6.5, first step in absorption

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8
Q

Carrier Mediated absorption of Folate

A

Proton Coupled Folate Transporter (transmembrane protein on apical surface of enterocyte), saturable in dietary range of concentration (low compared to supplement)

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9
Q

Proton Couple Folate Transporter

A

on enterocyte’s apical membrane, for folate absorption, uni-directional, transports folates at acidic pH, same affinity for reduced folates and folic acid

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10
Q

Non saturable Absorption of Folate

A

pharmacological range (high dose supplements), without a transporter, because synthetic folic acid does not need GCPII (skip a step)

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11
Q

Alcoholism

A

decreases GCPII and PCFT in folate absorption, decreases thiamin transporter 2 and 1 activity

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12
Q

5-methyl THF

A

blood circ. form, >50% bound to albumin, cells absorb as monoglutamate but store as polyglutamate for enzymes, its only reaction is with MS, methylated by liver or enterocyte by MTHFR

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13
Q

Folate bioavailability

A

~50% folate absorbed (bc food matrix), 100% folic acid supplement, ~85% enriched foods

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14
Q

Dietary Folate Equivalents

A

DFE: 1.7 * mcg folic acid + mcg folate = mcg DFE, for supplements multiply by 2 instead

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15
Q

Reduced Folate Carrier

A

RFC: cell-surface transmembrane protein that transports folate optimally at pH 7.4, used only for peripheral tissue uptake, bi-directional, higher affinity for reduced folates (THF) than folic acid

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16
Q

Methionine Synthase

A

demethylates 5-methyl-THF once in enterocyte for storage (before converting into polyglutamate, methylates homocysteine into methionine, regenerates THF, “remethylation” pathway, uses methylcobalamin (B12)

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17
Q

Folypolyglutamate synthetase

A

converts THF monoglutamate to polyglutamate n intestinal cell to retain intracellular folate

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18
Q

Gamma-glutamyl hydrolase

A

converts THF polyglutamate into monoglutamate to release from enterocyte back into portal blood circulation (like as bile), most is re-absorbed so little is excreted

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19
Q

Folate Storage Amount

A

15-30 mg

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20
Q

Folate Excretion

A

as metabolites of cleavage of folate at 9-10 bond, <1% excreted in urine

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21
Q

Serine Hydroxymethyltransferase

A

SHMT: Serine donates 1 C to THF to become glycine and make 5,10-methylene THF, reversible, uses PLP (B6), R-group conversion

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22
Q

Methylenetetrahydrofolate Reductase

A

MTHFR: 5,10-methyleneTHF partially reduces to 5-methylTHF, irreversible, if 677T instead of C - higher risk for NTD if folate deficient

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23
Q

MTHFR 677C to T Polymorphism

A

~12% Caucasian (low), high in Hispanics and Asians, low in African Americans, valine instead of alanine, lower MTHFR activity, lower concentration of 5-methyl-THF in blood/cells, greater risk for NTD and CVD

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24
Q

S-adenosyl methionine (SAM)

A

source of methyl groups for >100 reactions, made after remethylation reaction with methionine synthase and activation of methionine with ATP

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25
Q

Thymidylate

A

synthesized from 5,10-methyleneTHF and dUMP to make dTMP (thymidylate) and DHF, pyrimidine synthesis to make Thymine

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26
Q

Dihydrofolate Reductase

A

reduces DHF to THF in thymidylate synthesis, chemotherapy targets it higher affinity for methotrexate (because of folate’s role in cell division)

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27
Q

Methotrexate

A

structure similar to folic acid (oxidized monoglutamate), when under chemotherapy, DHF reductase uses methotrexate instead of DHF, has NH2 instead of OH group at C4

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28
Q

10-Formyl-THF

A

contributes to carbons on purines (C2 and C8) of DNA

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29
Q

Plasma folate

A

earliest and most sensitive folate status indicator, short-term (hours)

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30
Q

RBC folate

A

long term indicator (120 day turnover), tissue stores

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31
Q

Homocysteine

A

functional indicator of folate, b12, severe b6 deficiency

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32
Q

Upper Limit Folic Acid

A

1000 DFE

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33
Q

Upper Limit Folate

A

none

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34
Q

Folate deficiency

A

< 3 ng/mL, increased NTD risk and congenital heart defect risk

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35
Q

NTD

A

spina bifida (spinal cord protrusion) or anencephaly (incomplete brain/head, more rare), when folate deficient during first 28 days of pregnancy, association between folate status and NTD found in 1960’s by Richard Smithells and in 1980’s with a multivitamin trial

36
Q

RJ Berry

A

CDC director for China NTD study after MRC trial, used 400 mcg supplement and no placebo group

37
Q

Folic Acid fortification

A

1998 FDA mandated enriched cereal grains and fried chicken, controversial because of cancer risk

38
Q

George Minot and William Murphy

A

1926: treats pernicious anemia in humans with beef liver, Nobel prize

39
Q

Atrophic Gastritis

A

chronic inflammation of gastric mucosa, autoimmune disorder where Ab destroy parietal cells (which make IF), most common cause of pernicious anemia

40
Q

Victor Herbert

A

discoveries with megaloblastic anemia, self-experimentation, methyl trap hypothesis for MTHFR reaction in B12/folate deficiency

41
Q

Cubulin

A

TCII receptor, IF receptor, important for B12 absorption

42
Q

Methylmalonyl CoA Mutase

A

MCM: in mitochondria of intestinal cells, catalyzes isomerization of methylmalonyl-CoA to succinyl-CoA in TCA, uses adenosylcobalamin (B12)

43
Q

Adenosylcobalamin

A

Co-CH2 bond weak/easily broken to form radical to take H from methylmalonyl-CoA via MCM, mostly stored in this form

44
Q

Megaloblastic anemia

A

folate/B12 deficiency impairs DNA synthesis, early erythroblasts do not divide (megalo) and go to bloodstream, they do not have much hemoglobin (anemia)

45
Q

Pernicious anemia

A

main causes of B12 deficiency due to lack of IF in stomach (usually because autoimmune disorder destroys parietal cells), 2-3% of elder population (rare in young), can be caused by gastrectomy

46
Q

Pernicious anemia treatment

A

intramuscular b12 injections (100-1000 mcg cyanocobalamin) at monthly intervals, or oral b12 supplement > 1000 mcg/day (passive absorption)

47
Q

Gastric atrophy

A

loss of stomach acid for extracting b12 from food, can absorb crystalline normally (has IF), effects >30% elderly, H. pylori cause

48
Q

Nitric Oxide

A

laughing gas, anesthesia, oxidizes cobalt in b12 (destruction), results in b12 deficiency –> spinal cord degeneration, used in dentistry

49
Q

Demyelenation of Nervous system

A

lack B12: low synthesis of SAM –> low methylation rxns –> low neurotransmitters & membrane phospholipids in myelin. Disrupted odd chain FA metabolism related to the increase in MMA & precursors

50
Q

Transulfuration

A

B6 function as cystathionine beta synthase (CBS) and cystathionine lyase to convert homocysteine (serine added) to cysteine

51
Q

Dopamine

A

neurotransmitter, depends on PLP (B6), important in cognition/motivation/punishment/reward, motor control, produced in neurons, Parkinson’s disease due to death of dopaminergic neurons (decarboxylation –> also heme biosynthesis)

52
Q

Transamination

A

B6, AA degradation, most transfer of amino groups to alpha-keto acids

53
Q

Amino group acceptors

A

alpha-ketoglutarate and pyruvate

54
Q

Christiaan Eijkman

A

studies beriberi in 1890s, received joint nobel prize with sire frederick gowland hopkins (B1)

55
Q

Casimir Funk

A

1911: coins term “vitamin” from vital amine, isolates anti-beriberi factor (b1), isolates nicotinic acid (b3)

56
Q

Robert Williams

A

synthesizes vitamin in 1935 and names it thiamin (sulfur containing compound)

57
Q

Albumin

A

binds vitamins for storage in serum, B6, B1 (thiamin), folate, B2 (riboflavin)

58
Q

Body stores thiamin

A

25-30 mg

59
Q

Wet beriberi

A

cardiomyopathy (heart muscle disease) and edema (swelling) from thiamin deficiency

60
Q

Dry beriberi

A

peripheral neuropathy from thiamin deficiency

61
Q

Wernicke-Korsakoff syndrome

A

brain disorder due to thiamin deficiency, most often in west hemisphere, triad of confusion/ataxia/ocular abnormalities

62
Q

Thiamin transporter 2

A

thiamin absorption into intestine, also cellular uptake by all cells

63
Q

Thiamin transporter 1

A

cellular uptake by all cells, NOT absorption into intestine

64
Q

Paul Karrer

A

isolates B2 and recognizes as “yellow enzyme” with ribose like side chain (yellow = flavus) and named B2 riboflavin, won nobel prize

65
Q

Pyridoxal oxidase

A

Pyridoxal (PL - B6) converted to 4-pyridoxic acid for excretion, dependent on B2

66
Q

Glutathione Reductase

A

sometimes ETC is leaky so oxygen is partially oxidized, important for antioxidant use, dependent on B2, used as B2 status indicator

67
Q

Glossitis

A

shiny tongue from riboflavin (b2) deficiency

68
Q

Pharmacologic Niacin (B3)

A

lowers LDL, increases HDL, lowers TG BUT no decrease in heart disease risk

69
Q

Pellagra

A

B3 (niacin) deficiency, most severe nutrient deficiency in US, dermatitis, Dr. Joseph Goldberger discovered that dietary deficiency was cause not infection, rough skin, dependence on corn countries

70
Q

Nicotinic acid first produced

A

oxidation of nictotine from Nicotiana tabacum (tobacco plant)

71
Q

Goldberger

A

discovered Pellegra is due to B3 deficiency not infection

72
Q

ADP Ribosylation

A

post-translational modification that adds an ADP ribosyl to enzymes, catalyzed by mono ADP ribosyl transferase (1-ADP ribosyl) and poly-ADP ribosyl polymerase

73
Q

Pyruvate carboxylase

A

Adds CO2 to pyruvate with biotin to make oxaloacetate for TCA cycle

74
Q

Propionyl Co-A Carboxylase

A

catabolism of amino acids isoleucine, threonine, and methionine, uses biotin, also beta-oxidation of fatty acids with odd numbered chain

75
Q

Acetyl CoA carboxylase I and II

A

first committed step of fatty acid synthesis, biotin

76
Q

Beta-methylcrotonyl CoA carboxylase

A

involved in leucine catabolism, biotin

77
Q

Biotin, non enzyme functions

A

cell cycle, biotinylation (epigenetics, attached to histone) for cell proliferation/gene silencing/cell response to DNA damage

78
Q

Nitrous Oxide

A

oxidizes cobalt in B12 to result in B12 deficiency

79
Q

Heme biosynthesis

A

decarboxylation with B6 as coenzyme

80
Q

Thiamin as coenzyme

A

Pyruvate-dehydrogenase, alpha-ketoglutarate dehydrogenase, branch chain alpha-ketoglutarate, transketolase

81
Q

Glycogen phosphorylase

A

PLP taken up by peripheral tissues in muscle, biggest stores of B6 in muscle because of it

82
Q

Transcobalamin 1

A

circulating storage form, most common transport protein, haptocorrin or R protein, is not involved in direct absorption into body

83
Q

Poly ADP-ribose polymerases

A

DNA repair, cell differentiation and apoptosis, PARP-1 modifies nuclear proteins by poly ADP-ribosylation, response to UVB radiation

84
Q

poly ADP ribosylation

A

riboflavin, impaired function of PARP-1 contributes to skin sensitivity to sun in pellagra

85
Q

Niacin equivalents

A

60 mg Trp = 1 mg niacin = 1 NE

86
Q

niacin status assessment

A

<0.5 mg/g creatinine

87
Q

Niacin and hyperlipidemia

A

lowers LDL, increases HDL, lowers TG, no effect on risk of heart attack

Nutrition and Metabolism (3 decks)

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