SYLLABUS 16: Methylation Reactions in Biological Systems: Vitamin B12 Metabolism Flashcards Preview

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Flashcards in SYLLABUS 16: Methylation Reactions in Biological Systems: Vitamin B12 Metabolism Deck (38):

is met essential or nonessential aa?




why is Met important

1. protein synthesis 

2. it's the major biological methylating agent used in synthesis of imp biochemicals 



what is SAM

s-adenosyl methionine, the methylating agent produced in the methionine adenosyl transferase rxn 

Met + ATP -> SAM + 3Pi 


what are some important compounds whose synthesis requires a methyl group from SAM?



methylated nucleotides 




what happens is SAM gives up its methyl group

converted to S-adenosyl homocysteine, SAH, which is hydrolyzed to adenoside + homocysteine 


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how can homocysteine become methionine again?

what inhibits this rxn?

homocysteine can accept a methyl group from the vitamin cofactors N5-methyl tetrahydrofolate and B12, cobalamine 


high levels of methionine inhibit this reaction b/c do not need to generate methionine

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what is the active methyl cycle

Methyl-tetrahydrofolate carries methyl group on N-5 of its structure 

N5-CH3-THF transfers the methyl group to vitamin B12, cobalamine => methyl cobalamine 

methyl cobalamine transfers the methyl to homocysteine => methionine 

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what is the purpose of the transulfuration pathway

to convert methionine -> homocysteine -> cysteine in conditions of sufficient methionine available, when do not need more methionine 



describe the transulfuration pathway 

1. homocysteine reacts w/ serine, forms cystathionine, via cytathionine synthase, a PLP requiring enzyme 

is feedback inhibited by high levels of cysteine

2. cystathionine is hydrolzed by cystahionase, also requires PLP, to cysteine + a-ketobutyrate 

a-ketobutyrate -> propionyl coA -> succinyl CoA -> TCA cycle 

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is serine an essential amino acide? 

is cysteine

serine: no 

cysteine: semi; can be biosynthesized from serine + met


when is propionyl CoA produced during aa metabolism?

from a-KB, which came from cystathione, which came from serine + methionine 

from valine, isoleucine, and threonin e 



what's the fate of succinyl CoA?

1. can be further oxidized in TCA cycle for energy 

2. can be metabolized to OAA and eventually to gulcose during gluconeogenesis 

3. can produce heme 


what does propionyl CoA -> succinyl CoA require?

vitamin B12 


what mammalian reactions require vitamin B12?

1. conversion of homocysteine -> methionine 

2. conversion of propionyl CoA -> succinyl CoA 


how is transulfuration pathway involved in oxidative stress mitigation?

it produces cysteine, which is 1 of 3 amino acids that make up GSH 

so large amounts of cysteine are needed for GSH, not just for protein synthesis 

thus transulfuration pathway is important as protectant against oxidative stress via cystein formation 


fates of homocysteine?

1) go back, become methionine

2) become cysteine  

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what is homocystinuria

metabolic inborn error of metabolism in which large amounts of homocysteine accumulate 



what does homocystinuria cause

neurological disorders/severe mental retardation

failure to grow and thrive 

skeletal abnormalities 

cardiovascular abnormalities 

dislocation lens sockets 




what causes homocystinuria

deficiency of vitamins B6, B12, or THF 

deficiencies in cystathione synthase or homocysteine methyl transferase 



how do you treat someone w/ homocystinuria?

if it's a vitamin cofactor that's missing, then give them supplement of the cofactor- B6, B12 

if the enzyme is deficient, though, must limit methionine in the diet, which is possible b/c it's an essential aa, and add cysteine to the diet since methione is limited and cystine comes from methionine


what are part of the toxic effects on the body of high levels of homocysteine?

1. elevated oxidative stress 

2. smooth muscle cell proliferation 


vitamin B12 structure? 

1 corrin ring of 4 pyrrole rings linked together, + central cobalt atom 

at "rest", 6th substituent: OH 


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what is the 6th substituent of Cobalt of Vitamin B12

1. at rest 

2. as a drug 

3. during digestion

4. as a vitamin cofactor?

1. at rest, = OH 

2. as a drug, = CN 

3. during digestion, = CN -> OH

4. vitamin cofactor, = methyl, methylcobalamine, or deoxyadenosine, deoxyadenosyl cobalamine



how is deoxyadenosyl B12 formed

Cobalamine, B12 + ATP -> deoxyadenosyl B12 + 3pi 

catalyzed by deoxyadenosyl transferase


in what reaction is deoxyadenosyl-B12 a cofactor

methylmalonyl mutase reaction when methylmalonyl CoA -> succinyl CoA


what's connection between methylmalonyl CoA and B12? 

propionyl CoA is made from the breakdown of 4 amino acids, isoleucine, valine, Met, Threonine, and odd-chain fatty acids 

Propionyl Co A -> D methyl-malonyl Co A -> L-methylmalonyl Co A -> succinyl Co A 

L-methylamlonyl CoA -> succinyl CoA requires using the cofactor form of Vitamin B12, Deoxyadenosyl to do a rearrangement reaction with a free radical intermediate which the mutase uses

without it get disease 


what causes methylmalonyl aciduria?

if the rearrangement reaction w/ free radical from L-methylmalonyl CoA -> succinyl CoA doesn't occur 

due to: 

1. absence of the mutase 

2. deficiency in vitamin B12 

3. defiency of the transferase that makes B12 


what does methylmalonyl aciduria result in?

severe mental retardation 


GI irritation 


treatment of methylmalonyl CoA? 

restrict Met, Val, The, Isoleucine in diet 


what causes pernicious anemia?

deficiency in vitamin B12


what are some critical biochem components which are produced from methylation rxns?

epinephrine, creatine, methylated nucleotides, phosphatidylcholine, and melatonin. 


what regulates whether homocysteine is converted to Met or Cysteine? is cysteine an essential amino acid? 

whether homocysteine is converted to methionine or cysteine is controlled by high
levels of methionine, which inhibit homocysteine from becoming methionine

cysteine is thus essential when met is high


what cofactors are needed for homocystein methyl transferase (methionine synthase) reaction? 

N5-methyl-THF and B12


how can you treat homocystenuria? 

by either supplementing the patient’s diet with B6 or
B12 if it’s the cofactor that’s missing, or if it’s the enzyme that’s missing, then limit
methionine in the patient’s diet, and add in cysteine, since limiting methionine means
less cysteine will be produced 


what ultimately happens to the carbon skeleton of homocysteine (met) after transsulfuration? 

Through transsulfuration, the carbon skeleton of homocysteine is converted to aketobutyrate,
which is decarboxylated to propionyl CoA, which is metabolized to
succinyl CoA, which can be oxidized in the TCA cycle for energy, or metabolized to OAA
and eventually glucose via gluconeogenesis, or can produce heme. 


why is vitamin B12 necessary? what specific compounds require B12 for ultimate conversion to succinyl CoA? 

Vitamin B12 is necessary because it’s a crucial cofactor in many metabolic reactions –
including conversion of homocysteine to methionine and conversion of propionyl CoA to
succinyl CoA. L-methylmalonyl CoA requires Vitamin B12 as a cofactor to do a
rearrangement reaction involving B12 as a free radical intermediate to become Succinyl


what causes methylmalonyl aciduria and how is it treated? 

 Methylmalonyl aciduria is caused by a B12 deficiency, absence of the mutase, or
deficiency of the transferase that makes B12, any of which leads to inability to convert
L-methylmalonyl CoA to Succinyl CoA. This is treatable by restricting Met, Val, The, and
Isoleucine in the diet, since these are all precursors to Propionyl CoA. 


what causes pernicious anemia? how is it treated? 


stomach parietal cells make Intrinsic Factor which is needed to bind and absorb dietary B12 in the ileum 

pernicious anemia happens when you get autoimmune destruction of these parietal cells 

so the pathway to absorbing B12 gets disrupted 

treat by giving IV B12 or forms that can be absorbed w/o IF

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