Nitrogen IV Flashcards
What amino acids formed succinyl CoA?
- methionine
- valine
- isoleucine
- threonine
How is methionine used to make SAM?
- Methionine
Methionine + ATP—> SAM (S-adenosylmethionine)
SAM is the major methyl-group donor in 1-C metabolism
Explain in detail how methionine is made into SAM
ATP + methionine
Methionine adenosyl transferase. All three phosphates of ATP cleaved
Because the 🔼G of the reaction is very positive, and it must be overcome
All three phosphates of the ATP have been cleaved to force sulfur to hold a positive sulfur
How does sulfur usually occur in organic compounds?
Have 2 bonds, 2 lone pairs and no charge
Why does the sulfur in SAM have a positive charge?
The sulfur in SAM has a positive charge so it is activated, meaning it is chemically activated
What is SAM used for?
Required for methylation reactions that require movement of -CH3
Note that the reactions using SAM are different than moving 1 carbon groups with THF
What is the most reduced of the 1 carbon groups?
Methyl groups
What is the function of THF?
Moves carbons in various. ‘Other’ oxidation states: (N- formyl, formyl, methenyl etc…)
What 2 pathways detoxify homocysteine?
- Methylate homocysteine to form methionine
- Transfer the sulfur of homocysteine (which was originally methionine) to serine to form cysteine (trans-sulfuration pathway)
Give a general description of detoxification of homocysteine
There are two major disposal pathways for homocystein. Conversion to methionine requires folate and vitamin B12 -derived coenzymes and is a remethylation process. The formation of cysteine requires vitamin B6 (pyroxidine) and is a trans sulfuration process- the sulfur of methionine becomes the sulfur of cysteine
How can vitamin B6 be used to detoxify homocysteine?
- Cystathionine synthetase and cystathionase both require pyridoxal phosphate. (Vitamin B6)
- cystathionine beta-synthetase converts L-homocysteine to cystathionine (this part of reaction uses L-serine to make water
- cystathionine converted to L-cysteine
Enzyme: y-cystathionase
This second part of the reaction uses water and releases a-ketobutyrate + NH4+
Why do Cystathionine synthetase and cystathionase both require pyridoxal phosphate. (Vitamin B6)?
Vitamin B6 (pyridixal phosphate ) helps to move around the function group (in this case the sulfur)
What is the role of methyl THF?
The major role of methyl-THF is to support conversion of homocysteine into methionine
Resynthesis of methionine (methionine synthase)
-requires vitamin B12 and methyl-folic acid (THF-methyl)
What does deficiency of vitamin B12 lead to?
Deficiency of vitamin B12 results in homocysteine accumulation and also the trapping of THF in the methyl-THF form (which is not useful for most reactions)
Why does nature use vitamin B12?
Cobalamin
Cobalt is toxic, so nature uses B12 to (in a sense) put the cobalt “in a cage”
Enzymes hold B12 so that methyl groups can be moved around from a donor, to an acceptor substrate
Used to convert toxic homocysteine back to methionine
Methyl-THF + B12+ homocysteine—> methionine + empty THF
What causes homocystinuria ?
Homocystinuria occurs due to a deficiency of cystathionine beta-synthase or homocysteine N-methyl transferase
What are the features of homocystinuria?
Features: lens dislocation after age 3 and other ocular problems
- Childhood onset osteoporosis
- intellectual disability
- Atheroma formation due to oxidized lipid deposits (cardiovascular)
- Homocysteine can have other effect: lipid oxidation and platelet aggregation—> leads to fibrosis and calcification of atherosclerotic plaques
Summarize how valine and isoleucine be converted to propionate-CoA
First: must get the N off of the amino acid so that it can enter a catabolic pathways (transamination). Now there is a branched-chain alpha keto acid
Then: oxidative decarboxylation: (branched chain a-keto acid dehydrogenase coenzymes: NAD, CoA, TPP, lipoic acid, FAD)- must activate the BC-alpha keto acid by forming the CoA derivative (same as we saw with Pyruvate DH complex)
In the end, we must discuss the fate of propinoyl CoA
Importaht: propinoyl CoA has 3 carbons
What leads to maple syrup disease?
Oxidative decarboxylation of branched chain acids is deficient in maple syrup urine diseases
Explain the final step of Succinate CoA(from propinoyl CoA )
- Propinoyl CoA is converted to D-methylmalonyl-CoA via Propinoyl CoA carboxylase + Biotin /CO2
- methylmalonyl CoA has 4 carbons but it is toxic and a dead end metabolite
D-methylmalonyl converted to L-methylmalonyl
Methylmalonyl -CoA mutase (enzyme ) +vitamin B12cam remove a methyl group from methylmalonyl CoA, and put it back on the same molecule, but in a different position, thus forming succinyl CoA
Deficiency of the alpha keto acid dehydrogenase complex causes…
Maple syrup disease (MSUD)
How is maple syrup disease caused?
Caused due to deficiency of alpha keto acid dehydrogenase (neurological problems, keto sis, hypotonia, seizure)
- propionyl carboxylase requires biotin
- methylmalonyl CoA metacentric requires B12
What amino acids form Acetyl CoA or acetoacetate?
Leucine —> acetate (strictly ketogenic)
Lusine —> Acetyl CoA (strictly ketogenic)
Several other amino acids can be both keto and glucogenic
