Nitrogen 5

Question 1

How can alanine, Aspartate and Glutamate be synthesized?

Answer 1

From Pyruvate, OAA and a-KG via transamination

Glu can be synthesized by dehydrogenase enzymes, reductive amination

Glu is the most versatile amino acid

Question 2

How can serine be formed?

Answer 2

From 2-phosphoglycerate(an intermediate in glycolysis)
-a few reaction then transamination)

Serine can also be formed from glycine by transfer of hydroxyethyl group

Question 3

Explaine the synthesis of glutamine from histidine

Answer 3

• donation of a 1-carbon group to THF (to support anabolic/biosynthetic reactions)
• formation of glutamate-part of a general strategy to collect nitrogen into glutamate/glutamine fir eventual disposal in the urea cycle

Question 4

How is folic acid important in metabolism of nucleotides and amino acids?

Answer 4

• THF (Tetrahydrofuran) is the active form of folic acid produced by dihydrofolate reductase in a 2-step reaction
  
  • requires NADPH
• The 1-C unit may be carried by THF in different ways
  
  • bound to N N5 or N10 or both

-Folic acid deficiency increases the risk of spina bifida

Question 5

How is folic acid synthesized?

Answer 5

Folic acid is synthesized in bacteria and plants: essential vitamin 8n humans

• THF is the active form of folic acid
• Produced by dihydrofolate reductase (enzyme)
• Requires NADPH (electron donors)

Question 6

How is serine and glycine interconverted?

Answer 6

Ser —> glycine and N5 and N10-methylenetetrahydrofolic acid by serine hydroxymethyltransferase

Question 7

Explain folic acid in nucleotide and amino acid metabolism

Answer 7

• THF (tetrahydrofolate) is the active form of folic acid produced by dihydrofolate reductase in a 2-step reaction
  
  • Requires NADPH
• The 1-C unit may be carried by THF in different ways
  
  • bound N N15 or N10 or both

-folic acid deficiency increases the risk of spina bifida

Question 8

What are the inhibitors of folate and THF?

Answer 8

These can be used as drugs

Antibiotics-Sulfonamides competitively inhibit the synthesis of folic acid in microorganisms and, thereby, decrease the synthesis of nucleotides needed for the replication of DNA

Cancer chemo, and affecting immune cell function- Dihydrofolate reductase is constitutively inhibited by methotrexate, a folic acid analogue used to treat psoriasis, rheumatoid arthritis and neoplasticism diseases

Question 9

Why does vitamin b12 have cobalt?

Answer 9

Useful for moving /transferring methyl groups

Question 10

What are the functions of b12?

Answer 10

1. HomocysteineN-methyltransferase (methionine synthase)

• for resynthesis of methionine from homocysteine,
• Allows methyl-THF to become ‘empty’ so it can accept 1-carbon from an amino acid during its degradation
• This is the only (or only significant) reaction for methyl-THF

2. Methylmalonyl-CoA mutate reaction
   - Isomerization of methylmalonyl-CoA
   - Methylmalonyl-CoA derived from odd-chain fatty acid oxidation, and metabolism of isoleucine, valine and methionine
   - Also other sources

Question 11

Describe pathways to get rid of homocysteine

Answer 11

There are 2 major pathways. 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 transilfuration process

Question 12

Describe propionyl CoA

Answer 12

Oxidation of odd chain fatty acids, and degradation of valine, isoleucine and methionine generates propionyl CoA (3-carbons)

Propionyl CoA requires biotin and CO2

Methylmalonyl CoA mutate is one of 2 mammalian enzymes that use a cobalamin b12 group