Lecture 4 (2B) - Amino Acid Biosynthesis Flashcards
Many amino acids are not made by humans
(only plants and microorganisms)
known as essential amino acids
Nonessential amino acids
made by humans
Tyrosine “misclassified”
- from phenylalanine that’s essential
- disease of last lecture (alkaptonuria, phenylketonuria)
- can’t make it if no phenylalanine comes from outside
Other than the urea cycle, arginine
from outside
Nonessential amino acids come from 4 common intermediates
- pyruvate
- oxaloacetate
- α-ketoglutarate
(associated with citric acid cycle)
- 3-phosphoglycerate
(glycolysis - toward citric acid cycle but not associated)
Use of transamination
- pyruvate (ketone) → alanine (amino acid)
- oxaloacetate (ketone) → aspartate → asparagine
- α-ketoglutarate (ketone) → glutamate → glutamine
Process of transamination
- remove amide group from 1 amino acid → forms α-ketoacid
- place amide group on another α-ketoacid → forms another amino acid
- also similar for side chains
- amide through ketone to another
Citric acid metabolisms
catabolism of amino acids (to make others)
biosynthesis of other small molecules
GLUTAMATE to PROLINE
4 steps
glutamate **→* **glutamate-5-phosphate → glutamate-5(γ)-semialdehyde → Δ’-pyrroline-5-carboxylate → proline
* = steps between
- activation in the form of acyl-phosphate intermediate
- not seen because highly unstable (highly reactive)
- channels unstable intermediate between sites → can’t be seen (keep from doing side reactions)
GLUTAMATE to PROLINE
key points
- glutamate-5-phosphate is unstable
- not seen, only implied
- multi-enzyme system
- kept within structure
GLUTAMATE to ORNITHINE
3 steps
- get to glutamate-5(γ)-semialdehyde (2 steps through intermediate)
- from there branch to ornithine
OR
GLUTAMATE to ARGININE
GLUTAMATE to ARGININE
5 steps then urea cycle
glutamate
→
N-acetylglutamate
(in control of urea cycle)
(activation)
→
N-acetylglutamate-5-phosphate
→
N-acetylglutamate-5-semialdehyde
→
N-acetylornithine
→
ornithine
→
urea cycle
→
arginine
3-phosphoglycerate
forms:
- serine
- cysteine
- glycine
_3-PHOSPHOGLYCERATE _to GLYCINE
- to serine → 3 steps
(oxidation to activate, transamination, hydroxyl comes in)
(makes amino acid backbone)
- from serine to cysteine → 2 steps
(methionine breakkdwon, add H2O, remove H2O)
(serine = mainchain backbone to make cysteine)
- from serine to glycine
serine + THF → Glyine + N5-methyl-THF + H2O
similar processes are linked to different molecules
Essential amino acids
- the aspartate family
- the pyruvate family
- the aromatic amino acids
Essential amino acids
the Aspartate family
- lysine
- methionine
- threonine
Essential amino acids
the Pyruvate family
- leucine
- isoleucine
- valine
- valine and isoleucine have same pathways EXCEPT for the first step
- leucine from valine pathway
Essential amino acids
aromatic amino acids
- phenylalanine
- tyrosine
- tryptophan
- all have common precursor - CHORISMATE
CHORISMATE
to
PHENYLALANINE and TYROSINE
- shared first step
- chorismate → prephenate
- chemical makeup identical
- from prephenate → tyrosine
- through 4-hydroxy phenylpyruvate
- oxidation/reduction + decarboxylation (keep hydroxyl) → transamination
- from prephate to phenylalanine
- through phenylpyruvate
- decarnboxylation (lose hydroxyl) → transamination
CHORISMATE
(prephenate)
to
TYROSINE
prephenate → tyrosine
- through 4-hydroxyplenylpyruvate
- oxidation/reduction + decaroxylation (keep hydroxyl) → transamination
CHORISMATE
(prephenate)
to
PHENYLALANINE
prephenate → phenylalanine
- through phenylpyruvate
- decarboxylation (lose hydroxyl) → transamination
CHORISMATE
to
TRYPTOPHAN
- 6 step process by tryptophan synthase
- must channel molecules through sites to ensure it doesn’t drift off for something else
- removing pyruvate, adding amide
- adding a sugar
- sugar ring cleavage
- new ring fromed
- indole formed
- indole ring very reactive
- precursor to sidechain of tryptophan
- serine added
* to make main chain carbons (like cysteine)
→ tryptophan formed
Diseases
most concerned with catabolism (breakdown) of amino acids
Disease
L-serine deficiency
- feeding = missing low concentrations in testes
- 2 diseases form
- 3-phosphoserine phosphatase deficiency
- for phosphate activation
- exceptionally rare - only a single case
- rare because nonessential so very detrimental so usually die in womb