one carbon metabolism

Question 1

what three reactions is biotin a major carboxylase for, and what important steps do they do

Answer 1

Pyruvate carboxylase: 1st enzyme in gluconeogenesis
Acetyl coA carboxylase: 1st enzyme in fatty acid synthesis
Propionyl coA carboxylase: key enzyme in catabolism of BCAA

Question 2

what is biotin attached to in biotin carboxylase

Answer 2

attached to the eta amino group

Question 3

what does biotinidase do and how does deficiency in it express itself

Answer 3

cleaves biotin from proteins to be reused and from the lysine group after the carboxyl group has been transferred in biotin carboxylase

deficiency presents similar symptoms as biotin deficiency (seizures, hypotonia, ataxia)

Question 4

holocarboxylase synthetase does what and what does deficiency do

Answer 4

attaches biotin to a apocarboxylase making a holocarboxylase, which can then transfer carboxyl

deficiency results in encephalopathic crisis (brain damage) and hair loss

Question 5

what transfers most methyl groups in metabolism, and what are some of the things (general) that it methylates

Answer 5

S-Adenosylmethionine (SAM)

methylated DNA/RNA, epinephrine, protein bound lys, epinephrine, creatine, phosphatidylcholine

Question 6

S-adenosylmethionine is produced from what to compounds

Answer 6

methione and ATP (and PPi and Pi is also produced)

Question 7

after SAM delivers methyl group, what is left and happens to it

Answer 7

S-adenosylhomocysterine (SAH) which is converted in adenosine and homocysteine. returned to methionine by methionine synthase (B12)

Question 8

tetrahydrofolate (FH4) is created by

Answer 8

reducing folate (from folic acid B9) two times with NADPH

Question 9

in FH4, which N do methyl, formyl, methenyl and methylene bind to? (N5 or N10)

Answer 9

methyl (-CH3) N5
formyl (-CHO) N10
methenyl (-CH=) bridge N5 and N10
methylene (-CH2-) bridge N5 and N10

Question 10

which 4 amino acids does FH4 transfer C1 units from

Answer 10

trp, his, gly, and ser

formaldehyde and formate are intermediates in aa degredation

Question 11

5-methyl-FH4 is a notable FH4 derivative because

Answer 11

it is the lowest energy state and is not reversible to the other FH4 derivatives

Question 12

folic acid deficiency

Answer 12

affects rapidly deviding cells and can get large erythrcytes (macrocytic anemia). in pregnant women, embryo can have neural tube defects such as spina bifida

deficiency cause by improper diet (not enough raw veggies) or alcoholism

Question 13

how does methotrexate (MTX) work as a cancer drug

Answer 13

is an analog of folic acid that prevents dihydrofolate reductase, preventing the formation of FH4, and thus preventing rapid devision of tumor cells

Question 14

path of B12 from ingestion to blood

Answer 14

ingested in meat and dairy, proteases cleave from protein, bound by r-factor (haptocorrins) released by gastric mucosa, released by proteases and bound to intrinsic factor which take to receptor in ilium and delivers to blood (1//2 to liver and 1/2 to rest of tissues)

Question 15

B12 and methyl trap hypothesis

Answer 15

N5methyl-FH4 is most stable form of FH4, and only reaction that can remove met from it is B12 required methylation of homocysteine to produce methionine

(lack of B12 traps N5methyl-FH4 and get megoblastic anemia AND neurological deterioration)

Question 16

high homocysteine low b12 increases risk, what is this called, and what three things can cause it?

Answer 16

coronary heart disease, stroke (incr carotid plaque. called hyperhomocysteinemia.
can be caused by folate deficiency, B12 deficiency, mutation in cystathione beta-synthase

Question 17

mutations in cystathione beta-synthase cause what with what symptoms

Answer 17

cause hyperhomocysteinemia, in particularly homocysteinuria (extreme form), and symptoms similar to Marfan syndrome, and eye lens dislocation

Question 18

betaine pathway in alternate pathway to donate methyl to homocysteine to form Met not found in what region

Answer 18

in the brain and CNS (explain brain damage in B12 deficiency)

Question 19

causes of B12 deficiency and symptoms

Answer 19

vegan diet, pernicious anemia (lack of intrinsic factor), intestinal malabsorption (Crohn’s), bariatric surgery

causes megoblastic anemia (like folate), neurological symptoms (numbness, tingling, vertigo), elevated methymalonyl (BCAA break down)

Question 20

megaloblasts

Answer 20

type of macrocytic anemia of enlarged, misshapen blood cells in bone marrow (DNA synth inhib, but RNA cont), elevated hypersegmented neutrophils in peripheral blood.