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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
Thymidylate
synthesized from 5,10-methyleneTHF and dUMP to make dTMP (thymidylate) and DHF, pyrimidine synthesis to make Thymine
26
Dihydrofolate Reductase
reduces DHF to THF in thymidylate synthesis, chemotherapy targets it higher affinity for methotrexate (because of folate's role in cell division)
27
Methotrexate
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
28
10-Formyl-THF
contributes to carbons on purines (C2 and C8) of DNA
29
Plasma folate
earliest and most sensitive folate status indicator, short-term (hours)
30
RBC folate
long term indicator (120 day turnover), tissue stores
31
Homocysteine
functional indicator of folate, b12, severe b6 deficiency
32
Upper Limit Folic Acid
1000 DFE
33
Upper Limit Folate
none
34
Folate deficiency
< 3 ng/mL, increased NTD risk and congenital heart defect risk
35
NTD
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
RJ Berry
CDC director for China NTD study after MRC trial, used 400 mcg supplement and no placebo group
37
Folic Acid fortification
1998 FDA mandated enriched cereal grains and fried chicken, controversial because of cancer risk
38
George Minot and William Murphy
1926: treats pernicious anemia in humans with beef liver, Nobel prize
39
Atrophic Gastritis
chronic inflammation of gastric mucosa, autoimmune disorder where Ab destroy parietal cells (which make IF), most common cause of pernicious anemia
40
Victor Herbert
discoveries with megaloblastic anemia, self-experimentation, methyl trap hypothesis for MTHFR reaction in B12/folate deficiency
41
Cubulin
TCII receptor, IF receptor, important for B12 absorption
42
Methylmalonyl CoA Mutase
MCM: in mitochondria of intestinal cells, catalyzes isomerization of methylmalonyl-CoA to succinyl-CoA in TCA, uses adenosylcobalamin (B12)
43
Adenosylcobalamin
Co-CH2 bond weak/easily broken to form radical to take H from methylmalonyl-CoA via MCM, mostly stored in this form
44
Megaloblastic anemia
folate/B12 deficiency impairs DNA synthesis, early erythroblasts do not divide (megalo) and go to bloodstream, they do not have much hemoglobin (anemia)
45
Pernicious anemia
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
Pernicious anemia treatment
intramuscular b12 injections (100-1000 mcg cyanocobalamin) at monthly intervals, or oral b12 supplement > 1000 mcg/day (passive absorption)
47
Gastric atrophy
loss of stomach acid for extracting b12 from food, can absorb crystalline normally (has IF), effects >30% elderly, H. pylori cause
48
Nitric Oxide
laughing gas, anesthesia, oxidizes cobalt in b12 (destruction), results in b12 deficiency --> spinal cord degeneration, used in dentistry
49
Demyelenation of Nervous system
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
Transulfuration
B6 function as cystathionine beta synthase (CBS) and cystathionine lyase to convert homocysteine (serine added) to cysteine
51
Dopamine
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
Transamination
B6, AA degradation, most transfer of amino groups to alpha-keto acids
53
Amino group acceptors
alpha-ketoglutarate and pyruvate
54
Christiaan Eijkman
studies beriberi in 1890s, received joint nobel prize with sire frederick gowland hopkins (B1)
55
Casimir Funk
1911: coins term "vitamin" from vital amine, isolates anti-beriberi factor (b1), isolates nicotinic acid (b3)
56
Robert Williams
synthesizes vitamin in 1935 and names it thiamin (sulfur containing compound)
57
Albumin
binds vitamins for storage in serum, B6, B1 (thiamin), folate, B2 (riboflavin)
58
Body stores thiamin
25-30 mg
59
Wet beriberi
cardiomyopathy (heart muscle disease) and edema (swelling) from thiamin deficiency
60
Dry beriberi
peripheral neuropathy from thiamin deficiency
61
Wernicke-Korsakoff syndrome
brain disorder due to thiamin deficiency, most often in west hemisphere, triad of confusion/ataxia/ocular abnormalities
62
Thiamin transporter 2
thiamin absorption into intestine, also cellular uptake by all cells
63
Thiamin transporter 1
cellular uptake by all cells, NOT absorption into intestine
64
Paul Karrer
isolates B2 and recognizes as "yellow enzyme" with ribose like side chain (yellow = flavus) and named B2 riboflavin, won nobel prize
65
Pyridoxal oxidase
Pyridoxal (PL - B6) converted to 4-pyridoxic acid for excretion, dependent on B2
66
Glutathione Reductase
sometimes ETC is leaky so oxygen is partially oxidized, important for antioxidant use, dependent on B2, used as B2 status indicator
67
Glossitis
shiny tongue from riboflavin (b2) deficiency
68
Pharmacologic Niacin (B3)
lowers LDL, increases HDL, lowers TG BUT no decrease in heart disease risk
69
Pellagra
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
Nicotinic acid first produced
oxidation of nictotine from Nicotiana tabacum (tobacco plant)
71
Goldberger
discovered Pellegra is due to B3 deficiency not infection
72
ADP Ribosylation
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
Pyruvate carboxylase
Adds CO2 to pyruvate with biotin to make oxaloacetate for TCA cycle
74
Propionyl Co-A Carboxylase
catabolism of amino acids isoleucine, threonine, and methionine, uses biotin, also beta-oxidation of fatty acids with odd numbered chain
75
Acetyl CoA carboxylase I and II
first committed step of fatty acid synthesis, biotin
76
Beta-methylcrotonyl CoA carboxylase
involved in leucine catabolism, biotin
77
Biotin, non enzyme functions
cell cycle, biotinylation (epigenetics, attached to histone) for cell proliferation/gene silencing/cell response to DNA damage
78
Nitrous Oxide
oxidizes cobalt in B12 to result in B12 deficiency
79
Heme biosynthesis
decarboxylation with B6 as coenzyme
80
Thiamin as coenzyme
Pyruvate-dehydrogenase, alpha-ketoglutarate dehydrogenase, branch chain alpha-ketoglutarate, transketolase
81
Glycogen phosphorylase
PLP taken up by peripheral tissues in muscle, biggest stores of B6 in muscle because of it
82
Transcobalamin 1
circulating storage form, most common transport protein, haptocorrin or R protein, is not involved in direct absorption into body
83
Poly ADP-ribose polymerases
DNA repair, cell differentiation and apoptosis, PARP-1 modifies nuclear proteins by poly ADP-ribosylation, response to UVB radiation
84
poly ADP ribosylation
riboflavin, impaired function of PARP-1 contributes to skin sensitivity to sun in pellagra
85
Niacin equivalents
60 mg Trp = 1 mg niacin = 1 NE
86
niacin status assessment
<0.5 mg/g creatinine
87
Niacin and hyperlipidemia
lowers LDL, increases HDL, lowers TG, no effect on risk of heart attack

Nutrition and Metabolism (3 decks)

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