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IHN: Biochemistry 2 > one-carbon metabolism > Flashcards

one-carbon metabolism Flashcards

1
Q

one-carbon metabolism aka __ cycle

A

one-carbon metabolism aka folate cycle

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2
Q

production of glycine steps

A
  1. serine donates 1 carbon to THF (THF –> methylene-THF)
  2. this converts serine –> glycine (requires PLP, vit B6)
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3
Q

producing thymine

A
  1. methylene-THF –> DHF (1C donation, thymidylate synthase)
  2. thymidylic acid –> DNA-thymine
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4
Q

producing DHF

A

reducing folic acid (using NADPH)

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5
Q

producing THF

A

methylene-THF –> methyl-THF –> (requires B12) THF

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6
Q

__ is essential for production of THF

A

DHF is essential for production of THF

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7
Q

what catalyzes DHF reduction to THF

A

DFHR
requires NADPH

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8
Q

serine –> glycine requires

A

PLP (B6)

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9
Q

homocystein –> methionine requires

A

folate
B12
choline

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10
Q

folate and 1-carbon metabolism are important for epigenetics bc

A

they make SAM, a methyl donor

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11
Q

folate is essential to make

A

DNA thymine

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12
Q

DNA-adenine and guanine production

A
  1. serine donates 1C to THF (THF –> methylene THF)
  2. methylene THF –> formyl THF
  3. formyl THF is a 1C donor for DNA adenine and guanine
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13
Q

low riboflavin inhibits ability to make

A

DNA adenine and DNA guanine

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14
Q

how do we know to stop making methionine

A

SAM: indicates we have enough dietary methionine

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15
Q

fasting = __ SAM = make __ methionine

A

fasting = less SAM = make more methionine

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16
Q

producing Methionine, SAM, and homocysteine

A
  1. THF –> methylene-THF (serine donates 1C)
  2. methylene-THF –> methyl-THF (MTHFR) (requires riboflavin)
  3. homocysteine –> methionine (methyl-THF donates 1C) (needs B12)
  4. Methionine –> SAM (needs ATP)
  5. SAM –> homocysteine (B12)
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17
Q

B9/B12 independent methionine production

A

betaine (made from choline) can convert homocysteine to Met

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18
Q

formation of cysteine

A
  1. homocysteine –> cysteine (requires PLP)
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19
Q

__ inhibits MTHFR and stimulates CBS
this pushes us to use more __ to make more __

A

SAM inhibits MTHFR and stimulates CBS
this pushes us to use more methionine to make more cysteine

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20
Q

vitamin B6 supplement form

A

pyridoxine

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21
Q

vitamin B6 active cofactor

A

PLP

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22
Q

vitamin B6 excretion form

A

pyridoxic acid

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23
Q

how does B6 cross cell?

A

B6 is bulky so it is dephosphorylated to cross, then rephosphorylates and sent to blood

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24
Q

vitamin B6 rxns (5)

A
  1. transaminations
  2. decarboxylations
  3. heme synthesis
  4. one-carbon metabolism
  5. lipid and carb metabolism
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25
Q

vit B6 deficiency (4)

A
  1. microcytic anemia
  2. convulsions/EEG abnormalities
  3. hyperhomocysteinemia
  4. inflammatory disease
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26
Q

microcytic anemia =

A

smaller RBC that are pale (white in middle)
iron deficiency

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27
Q

low vit B6 = low pyridoxal phosphate = __ GABA = __

A

low vit B6 = low pyridoxal phosphate = decreased GABA = seizures

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28
Q

low pyridoxal phosphate can also cause decreased __, leading to __

A

low pyridoxal phosphate can also cause decreased serotonin, leading to depression

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29
Q

vit B6 and inflammation

A

low B6 = reduced PLP = increased inflammation

30
Q

microcytic anemia cause
macrocytic anemia cause

A

microcytic anemia B6 deficiency
macrocytic anemia B9, B12 deficiency

31
Q

vit B6 is associated with

A

blood

32
Q

__ and __ are required in heme synthesis

A

vit B6 and iron are required in heme synthesis

33
Q

measuring vit B6 status

A

plasma PLP concentration
(less common) measure PLP-dependent enzyme activity
oral Met to Trp loading tests

34
Q

methionine load test
if you have a defect in enzyme,

A

homocysteine rises and won’t go down for awhile

35
Q

tryptophan load test
in deficiency,

A

lots of xanthurenic acid is produced, bc there is no B6 to go down normal pathway

36
Q

folic acid aka __ acid

A

folic acid aka pteroylglutamic acid

37
Q

synthetic (unnatural) form of folate

A

folic acid
pteroylglutamic acid

38
Q

folate is important in

A

DNA synthesis

39
Q

anti-folate drugs

A

impair DNA synthesis
good for cancer, rheumatoid arthritis in small doses (anti-inflammatory)

40
Q

dietary form of folate

A

PGA

41
Q

folate is attached to

A

glutamic acid

42
Q

reduced active form of folate is

A

THF

43
Q

in high doses, how is folic acid transported

A

passive diffusion

44
Q

which intestinal cell is folate transported across?

A

jejunum

45
Q

folate absorption

A
  1. remove glutamic acid residues so folate is less bulky
  2. PGA1 enters cell via H+ symporter
  3. PGA1 converted to reduced forms (aka methyl-THF)
  4. intestinal cell uses reduced folate or transports to portal circ
  5. FA can also directly enter in high doses via diffusion
46
Q

3 functions of folate

A

1- carbon metabolism
1. DNA and RNA synthesis (TAG)
2. methionine recycling
3. SAM synthesis

47
Q

folate deficiency

A

macrocytic (megaloblastic) anemia
hyperhomocysteinemia
NTDs

48
Q

macrocytic anemia

A

larger blood cells with increased number of lobes

49
Q

vitamin B12 aka

A

cobalamin

50
Q

2 cofactor forms of cobalamin

A

methyl
deoxyadenosyl

51
Q

vitamin B12 absorption

A
  1. B12 enters stomach attached to salivary R-binder
  2. parietal cells produce intrinsic factor: binds B12 in small intestine (duodenum)
  3. in ileum, B12 binds receptor, is absorbed (endocytosed) into lysosome
  4. lysosome released B12, sent into blood, bind to TC (trans-cobalamin) and is sent to tissues that need it
52
Q

vit B12 functions (2)

A
  1. 1- carbon metabolism
  2. odd-chain fatty acid metabolism
53
Q

vit B12 has same functions as

A

folate

54
Q

vitamin B12 deficiency

A

macrocytic (megaloblastic) anemia
hyperhomocysteinemia
neurological disease

55
Q

pernicious anemia

A

autoimmune disorder: loss of IF in stomach
leads to malabsorption of vit B12

56
Q

assessment of B12 status

A

serum B12 bound to haptocorrin and transcobalomin

57
Q

vit B12 malabsorption

A
  • Atrophic gastritis
  • Autoimmune production of IF or
    parietal cell antibodies (pernicious
    anemia)
  • Gastrectomy leading to loss of intrinsic factor
  • Pancreatic insufficiency
  • Bacterial overgrowth (H. Pylori)
  • HIV infection
  • Ileal disease and resection
58
Q

methyl-folate trap

A

low dietary methionine = not enough SAM = methylation rxns can’t happen

59
Q

intracellular vit B12 metabolism

A
  1. transcobalamin takes vit B12 to cells
  2. B12-cobalamin reduced to methyl-B12 (coenzyme for Met synthesis)
  3. some B12 in mito becomes adenosyl-B12 and is used to make succinyl-CoA
60
Q

treating macrocytic anemia

A

you must find out if deficiency in vit B9 or B12 has caused it
treating vit B12 with folic acid causes neurological damage exacerbated by vit B12 deficiency

61
Q

why does vit B12 deficiency cause the same problem as folate deficiency?

A

methyl-folate trap

62
Q

methyl-folate trap

A

when folate –> methyl-THF it can only be used as a methyl-donor to convert homocysteine into methionine which requires B12
if you are low in B12, methyl-THF builds up
methyl-THF can’t be converted back to methylene-THF, so methyl-THF is trapped

63
Q

what is the worst treatment for someone with vit B12 deficiency

A

folic acid!

64
Q

2 causes of vit B12 deficiency

A
  1. dietary deficiency
  2. malabsorption
65
Q

dietary deficiency of vit B12

A
  1. vegans and vegetarians
  2. low intake of animal foods
  3. takes years after strict vegan diet
66
Q

malabsorption caused vitamin deficiency

A
  1. pernicious anemia
  2. atrophic gastritis
67
Q

pernicious anemia

A

autoimmune disorder
no IF in stomach
can’t absorb pills or food vit B12

68
Q

atrophic gastritis

A

loss of stomach acid
can’t absorb B12
usually mild deficiency

69
Q

homocysteine increases risks of __ and __

A

homocysteine increases risks of atherosclerosis and myocardial infarction (MI)

70
Q

B vitamin supplements cause lowered __ which reduces __

A

B vitamin supplements cause lowered homocysteine which reduces brain atrophy

71
Q

PPIs like omeprazole inhibits transport of __ produced from parietal cells into lumen of stomach
SO, they can’t extract __

A

PPIs like omeprazole inhibits transport of H+ produced from parietal cells into lumen of stomach
SO, they can’t extract B12

72
Q

metformin may interfere with absoprtion of __ complex by interfering with __ requirement for that absorptive process

A

metformin may interfere with absoprtion of vit B12-IF complex by interfering with Ca2+ requirement for that absorptive process

IHN: Biochemistry 2 (38 decks)

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