one-carbon metabolism Flashcards
1
Q
one-carbon metabolism aka __ cycle
A
one-carbon metabolism aka folate cycle
2
Q
production of glycine steps
A
- serine donates 1 carbon to THF (THF –> methylene-THF)
- this converts serine –> glycine (requires PLP, vit B6)
3
Q
producing thymine
A
- methylene-THF –> DHF (1C donation, thymidylate synthase)
- thymidylic acid –> DNA-thymine
4
Q
producing DHF
A
reducing folic acid (using NADPH)
5
Q
producing THF
A
methylene-THF –> methyl-THF –> (requires B12) THF
6
Q
__ is essential for production of THF
A
DHF is essential for production of THF
7
Q
what catalyzes DHF reduction to THF
A
DFHR
requires NADPH
8
Q
serine –> glycine requires
A
PLP (B6)
9
Q
homocystein –> methionine requires
A
folate
B12
choline
10
Q
folate and 1-carbon metabolism are important for epigenetics bc
A
they make SAM, a methyl donor
11
Q
folate is essential to make
A
DNA thymine
12
Q
DNA-adenine and guanine production
A
- serine donates 1C to THF (THF –> methylene THF)
- methylene THF –> formyl THF
- formyl THF is a 1C donor for DNA adenine and guanine
13
Q
low riboflavin inhibits ability to make
A
DNA adenine and DNA guanine
14
Q
how do we know to stop making methionine
A
SAM: indicates we have enough dietary methionine
15
Q
fasting = __ SAM = make __ methionine
A
fasting = less SAM = make more methionine
16
Q
producing Methionine, SAM, and homocysteine
A
- THF –> methylene-THF (serine donates 1C)
- methylene-THF –> methyl-THF (MTHFR) (requires riboflavin)
- homocysteine –> methionine (methyl-THF donates 1C) (needs B12)
- Methionine –> SAM (needs ATP)
- SAM –> homocysteine (B12)
17
Q
B9/B12 independent methionine production
A
betaine (made from choline) can convert homocysteine to Met
18
Q
formation of cysteine
A
- homocysteine –> cysteine (requires PLP)
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
20
Q
vitamin B6 supplement form
A
pyridoxine
21
Q
vitamin B6 active cofactor
A
PLP
22
Q
vitamin B6 excretion form
A
pyridoxic acid
23
Q
how does B6 cross cell?
A
B6 is bulky so it is dephosphorylated to cross, then rephosphorylates and sent to blood
24
Q
vitamin B6 rxns (5)
A
- transaminations
- decarboxylations
- heme synthesis
- one-carbon metabolism
- lipid and carb metabolism
25
vit B6 deficiency (4)
1. microcytic anemia
2. convulsions/EEG abnormalities
3. hyperhomocysteinemia
4. inflammatory disease
26
microcytic anemia =
smaller RBC that are pale (white in middle)
iron deficiency
27
low vit B6 = low pyridoxal phosphate = __ GABA = __
low vit B6 = low pyridoxal phosphate = **decreased** GABA = **seizures**
28
low pyridoxal phosphate can also cause decreased __, leading to __
low pyridoxal phosphate can also cause decreased **serotonin**, leading to **depression**
29
vit B6 and inflammation
low B6 = reduced PLP = increased inflammation
30
microcytic anemia cause
macrocytic anemia cause
microcytic anemia **B6 deficiency**
macrocytic anemia **B9, B12 deficiency**
31
vit B6 is associated with
blood
32
__ and __ are required in heme synthesis
**vit B6** and **iron** are required in heme synthesis
33
measuring vit B6 status
plasma PLP concentration
(less common) measure PLP-dependent enzyme activity
oral Met to Trp loading tests
34
methionine load test
if you have a defect in enzyme,
homocysteine rises and won't go down for awhile
35
tryptophan load test
in deficiency,
lots of xanthurenic acid is produced, bc there is no B6 to go down normal pathway
36
folic acid aka __ acid
folic acid aka **pteroylglutamic** acid
37
synthetic (unnatural) form of folate
folic acid
pteroylglutamic acid
38
folate is important in
DNA synthesis
39
anti-folate drugs
impair DNA synthesis
good for cancer, rheumatoid arthritis in small doses (anti-inflammatory)
40
dietary form of folate
PGA
41
folate is attached to
glutamic acid
42
reduced active form of folate is
THF
43
in high doses, how is folic acid transported
passive diffusion
44
which intestinal cell is folate transported across?
jejunum
45
folate absorption
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
3 functions of folate
1- carbon metabolism
1. DNA and RNA synthesis (TAG)
2. methionine recycling
3. SAM synthesis
47
folate deficiency
macrocytic (megaloblastic) anemia
hyperhomocysteinemia
NTDs
48
macrocytic anemia
larger blood cells with increased number of lobes
49
vitamin B12 aka
cobalamin
50
2 cofactor forms of cobalamin
methyl
deoxyadenosyl
51
vitamin B12 absorption
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
vit B12 functions (2)
1. 1- carbon metabolism
2. odd-chain fatty acid metabolism
53
vit B12 has same functions as
folate
54
vitamin B12 deficiency
macrocytic (megaloblastic) anemia
hyperhomocysteinemia
neurological disease
55
pernicious anemia
autoimmune disorder: loss of IF in stomach
leads to malabsorption of vit B12
56
assessment of B12 status
serum B12 bound to haptocorrin and transcobalomin
57
vit B12 malabsorption
* 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
methyl-folate trap
low dietary methionine = not enough SAM = methylation rxns can't happen
59
intracellular vit B12 metabolism
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
treating macrocytic anemia
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
why does vit B12 deficiency cause the same problem as folate deficiency?
methyl-folate trap
62
methyl-folate trap
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
what is the worst treatment for someone with vit B12 deficiency
folic acid!
64
2 causes of vit B12 deficiency
1. dietary deficiency
2. malabsorption
65
dietary deficiency of vit B12
1. vegans and vegetarians
2. low intake of animal foods
3. takes years after strict vegan diet
66
malabsorption caused vitamin deficiency
1. pernicious anemia
2. atrophic gastritis
67
pernicious anemia
autoimmune disorder
no IF in stomach
can't absorb pills or food vit B12
68
atrophic gastritis
loss of stomach acid
can't absorb B12
usually mild deficiency
69
homocysteine increases risks of __ and __
homocysteine increases risks of **atherosclerosis** and **myocardial infarction (MI)**
70
B vitamin supplements cause lowered __ which reduces __
B vitamin supplements cause lowered **homocysteine** which reduces **brain atrophy**
71
PPIs like omeprazole inhibits transport of __ produced from parietal cells into lumen of stomach
SO, they can't extract __
PPIs like omeprazole inhibits transport of **H+** produced from parietal cells into lumen of stomach
SO, they can't extract **B12**
72
metformin may interfere with absoprtion of __ complex by interfering with __ requirement for that absorptive process
metformin may interfere with absoprtion of **vit B12-IF** complex by interfering with **Ca2+** requirement for that absorptive process
