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Biochem > Ch 40 > Flashcards

Ch 40 Flashcards

(68 cards)

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1
Q

What can CO2 be transferred by

A

biotin

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2
Q

Carbon in lower levels of oxidation than CO2 can be transferred by

A

tetrahydrofolate (FH4) aka vit B12 and S-adenosylmethionine (SAM)

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3
Q

what is FH4 produced from

A

vitamin folate

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4
Q

what is the primary 1-carbon carrier in the body

A

FH4

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5
Q

where does FH4 obtain 1-carbon units

A

serine, glycine, histidine, formaldehyde, and formate

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6
Q

how can folate exist in several different forms

A

the 1-carbon unit can be oxidized or reduced

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7
Q

can a carbon reduced to methyl-FH4 be reoxidized

A

no

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8
Q

what is the term ‘folate’ used for

A

water-soluble B-complex vitamin that fxns in transferring single-carbon groups at various stages of oxidation

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9
Q

examples of uses of 1-carbon group pool

A

dUMP to dTMP, glycine to serine, precursers of purine bases, and vit B12

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10
Q

What 2 rxns is vit B12 involved in

A

1) rearrangement of methyl group of L-methylmalonyl CoA to form succinyl CoA 2) transfers methyl group from FH4 to homocysteine forming methionine

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11
Q

What is SAM produced from

A

methionine and ATP

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12
Q

fxn of SAM

A

transfers methyl group to precursors that form many cmpds like creatine, phosphatidylcholine, epinephrine, melatonin, methylated nucleotides, and methylated DNA

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13
Q

only rxn in which methyl-FH4 can donate the methyl group

A

creation of methionine from homocysteine

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14
Q

what occurs id vit B12 or FH4 levels are insufficient

A

homocysteine will accumulate

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15
Q

methyl trap hypothesis

A

occurs when vit B12 deficient, methyl unable to leave FH4; folate deficient even though normal amounts present

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16
Q

what does a folate deficiency lead to

A

megaloblastic anemia due to inability of blood cell precursors to synthesize DNA

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17
Q

schilling test

A

ingest radioactive Co60 crystallie vit B12 and 24 hour urine smpl collected; determine amount of B12 absorbed

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18
Q

5-fluorouracil as chemotherapy agent

A

pyrimidine analong which is converted in cells to FdUMP that causes thyminless death and prevent tumor growthl prevents dUMP to dTMP

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19
Q

what does elevation in methylmalonic acid indicate

A

suspect vit B12 deficiency

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20
Q

why are folate deficiencies common in chronic alcoholics

A

inadequate dietary intake, damage to intestines and brush border enzymes, defect in enterohepatic circulation, liver damage, kidney reabsorption

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21
Q

ineffective erythropoiesis

A

increased marrow cellularity, but decreased red cell production

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22
Q

coemnzyme that fxns in accepting 1-carbon groups

A

tetrahydrofolate polyglutamate aka FH4

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23
Q

3 main structural components of FH4

A

1) bicyclic pteridine ring 2) para-aminobenzoic acid 3) polyglutamate tail consisting of several glutamate residues joined in amide linkage

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24
Q

where is 1-carbon unit accepted/bound in FH4

A

N5 or N10 or both

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25
what does folic acid/folate refer to
most oxidized form of pteridine ring of FH4
26
what reduces folate to dihydrofolate to tertrahydrofolate
dihydrofolate reductase in cells; reduction is favored direction of rxn
27
how do sulfa drugs work against some bacterial infections
analogs of para-aminobenzoic acid and interfer with synthesis of folate
28
US recommended dietary allowance of folate
400 ug for adult men and women
29
good sources of folate
green leafy vegies, liver, yeast, legumes, some fruits
30
what form is the dietary folate from natural sources
reduced coenzyme form
31
how is folate absorbed
folate conjugases in lumen cleave off glutamate residues producing monoglumate form of folate which is absorbed
32
what happens to absorbed folate in intestinal cells
converted to N5-methyl-FH4 which enters portal vein and goes to liver
33
how does N5-methyl-FH4 travel in blood
loosely bound to albumin and other plasma proteins
34
how can folate deficiency be tested
histidine load test; if folate deficient, then FIGLU appears in urine in excess amounts
35
major carbon source of one-carbon groups in human
serine; hydroxylmethyl group transferred to FH4 via hydroxymethyltransferase
36
how is FIGLU (formiminoglutamate) produced
degradation of histidine
37
why does folate deficiency cause DNA synthesis issues
required in purine base systhesis at carbons 2 and 8; also hindered due to dTMP synthesis
38
how does the corrin ring in vit B12 differ from heme
2 of the 4 pyrrole rings are directly joined rather than by a methylene bridge
39
what is within the ring of vit B12 (aka cobalamin)
Cobalt; can for a bond with a ccarbon atom
40
what form is B12 in supplements
cyanobalamin in which a CN group is linked to the cobalt
41
what does methotrexate resemble
folate except an amino group on C4 and methyl on N10
42
what is methotrexate used for
anticancer drug; inhibit dihydrofolate reductase and prevent conversion of FH2 to FH4
43
major source of vit B12
dietary meat, eggs, dairy products, fish, poultry, and seafood
44
2 forms of ingested vit B12
free or bound to dietary proteins
45
what does free B12 bind
proteins known as R-binders (aka haptocorrins or transcobalamin I)
46
where are R-binders produced
salivary glands and gastric mucosa
47
what occurs to haptocorrins in the small intestine
pancreatic enzymes digest them and release B12 which then binds to intrinsic factor
48
what is intrinsic factor
a glycoprotein secreted by parietal cells in stomach
49
where does the intrinsic factor-vit B12 complex attach
specific receptors in ileum
50
Besides pernicous anemia, what other malfunctions can cause vit B12 deficiency
pancreatic insufficiency or high intestinal pH (too little stomach acid); both prevent degradation of R-binder-B12 complex, so B12 can't bind intrinsic factor
51
what rxns is S-adenosylmethionine (SAM) used in
add methyl groups to either O or N; more than 35 rxns require
52
What does folate add 1-carbon groups to
carbon or sulfur
53
examples of SAM use
guanidinoacetate to creatine, norepinephire to ephinephrine, acetylserotonin to melatonin, and nucleotides to methylated nucleotides; inactivation of catecholamines and serotonin
54
what does SAM form when it donates its methyl group
S-adenosylhomocysteine which is hydrolyzed to form homocysteine and adenosine
55
2 major clinical manifestations of vit B12 deficiency
1) hematopoietic due to folate metabolism 2) neurologic due to hypomethylation in nervous system
56
classical clinical presentation of neurologic issues in B12 deficiency
numbness and tingling of hands and feet, diminished vibratory and position sense, progression to spastic gait disturbance
57
what are neurologica symptoms in vit B12 deficiency caused from
hypomethylation due to inability to recycle homocysteine to methionine and from there to SAM
58
what is required for the synthesis of SAM
methionine-either obtained from diet or through homocysteine
59
how do methyl groups get trapped in N5-methyl-FH4
vit B12 deficiency or methionine synthase enzyme defect
60
how is homocysteine synthesized
S-adenosylhomocysteine (which is hydrolyzed to form homocysteine and adenosine)
61
2 fates of homocysteine
remethylated to methionine or condensed with serine to form cystathionine
62
2 routes to methionine production
N5-methyl FH4 requiring B12 or betaine donates a methyl group to homocysteine in liver
63
what does homocysteine to cystathionine require
PLP
64
What occurs with homocysteine if vit B12 not available
breaks down to form cystathionine which forms cysteine, which is has neg feedback causing accumulation of homocysteine
65
what occurs wih enzyme defect in N5, N10-methylene-FH4 to N5-methyl-FH4
N5-methyl-FH4 too low to convert homocysteine to methionine, causing homocystine elevation
66
what occurs when cystathionine B-synthase defect occurs or vit B 6 deficiency
homocysteine level elvated since conversion to methionine can't accomidate all the homocystine accumulated
67
what is choline oxidized to form
betaine aldehyde, which is oxidized to betaine (trimethylglycine); an alternative route for methionine producation in liver
68
how does folate deficiency reduce DNA synthesis
decreased availability of deoxythymidine and purine nucleotides

Biochem (3 decks)

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