Nitrogen in Amino Acid Synthesis Flashcards
Describe the production of glutamine
- NH4+ reacts with glutamate to produce glutamine using glutamine synthetase
- Glutamine synthetase = 2 step mechanism
Describe the 2 step mechanism of glutamine sythetase
- Step 1: Glutamate is phosphorylated to form γ-glutamyl phosphate
- step 2: Phosphorylation of glutamate creates a good leaving group that is easily displaced by ammonia
Describe the two steps involved in the assimilation of NH4+ into glutamate
- Step 1: NH4+ reacts with glutamate to produce glutamine using glutamine synthetase
- Step 2: Glutamine reacts with α-ketoglutarate to generate two molecules of glutamate
This is catalyzed by glutamate synthase in bacteria and plants
Are glutamine sythetase and glutamate synthase present in all animals?
- Glutamine sytnthetase = present in all organisms
- Glutamate synthase is NOT (only in plants and bacteria)
Describe the regulation of glutamine synthetase
- Cumulative regulation
- Alanine, glycine, and at least 6 end products of glutamine metabolism = allosteric inhibitors of glutamine synthetase
Alone each of these molecules produces only partial inhibition, all 8 together will shut down the enzyme
What are all amino acids derived from?
All amino acids are derived from intermediates of glycolysis, the citric acid cycle, or the pentos phosphate pathway
How does nitrogen enter the biosynthetic pathways of the TCA cycle, pentos phosphate pathway and glycolysis?
Glutamate and Glutamine
What are the 6 precursors of amino acid biosynthetic families?
- α-ketoglutarate
- 3-phosphoglycerate
- Oxaloacetate
- Pyruvate
- Ribose 5-phosphate
- Phosphoenolpyruvate and erythrose 4-phosphate
Describe the synthesis of proline
- Precursor: α-ketoglutarate
- Derived from glutamate
- Bacteria: glutamate —> proline
- Humans: glutamate —> glutamate γ-semialdehyde —> proline —> ornithine
Describe the synthesis of arginine
- Precursor: α-ketoglutarate
- Derived from glutamate
- Generated by the urea cycle (ornithine is an intermediate)
How is ornithine synthesized?
Ornithine is produced by the breakdown of arginine in the urea cycle
(It is also synthesized from glutamate γ-semialdehyde)
Describe the synthesis of serine
- Precursor: 3-phosphoglycerate
- Same pathway in all organisms
- 3 steps
What are the 3 steps involved in the synthesis of serine?
- Oxidation of 3-phosphoglycerate to form 3-phosphohydroxypyruvate
- Transamination of glutamate to form 3-phosphoserine
- Dephosphorylation of 3-phosphoserine to form free serine
What amino acid is serine the precursor for?
- Glycine
- Serine —> glycine by N5, N10-methylene-THF
BRIEFLY Describe the synthesis of cysteine
- Almost identical to serine
- Serine and cysteine differ by one atom
- Serine = oxygen
- Cysteine = sulfer
- Serine to cysteine = oxygen to sulfer
Describe the synthesis of cysteine from homocysteine
- Free homocysteine undergoes a reaction with serine catalyzed by cystathionine β-synthase to yeild cystathionine
- Cystathionine γ-lyase a PLP requiring enzyme catalyzes the removal of ammonia and cleavage of cystathionine to yield free cysteine
Describe the synthesis for, Asparagine, Methionine, Lysine, and Threonine
- Precursor: oxaloacetate
- Derived from aspartate
Asparagine = synthesized from the amination of aspartate
Describe the synthesis of alanine and aspartate
- Precursors: pyruvate and oxaloacetate
- Synthesized by the transamination from glutamate
Describe the synthesis of valine, leucine, and isoleucine
- Precursor: pyruvate
- Pyruvate reacts with TPP to form a resonance stabilized carbanion
- The carbanion can go in two directions (either combine two pyruvate to form valine and leucine OR combine with
α-ketobutyrate to form isoleucine) - Addition of nitrogen is the last step in these reactions
- The amino group is donated from a molecule of glutamate
Describe the synthesis of tyrosine, tryptophan, and phenylalanine
- Precursors: phosphoenolpyruvate and erythrose 4-phosphate
- Very complex chemistry (rings must be synthesized then closed then oxidized to create double bonds)
- Chorismate is a common intermediate
