Lecture Notes

Amino acid biosynthesis
Learning objectives:

1. Humans do not biosynthesise all AA (essential and non-essential AA)
2. Common intermediates used to biosynthesised AA
3. The biosynthesis of proline & ornithine via 2 different pathways
4. The biosynthesis of aromatic AA from common precurssors chorismata



LO1. HUMANS DO NOT BIOSYNTHESIS ALL AA (ESSESNTIAL AND NON ESSENTIAL AA)

Essential AA

 Many AA not made by humans
- but made by plants and micro-organisms
- known as essential AA
must be in human diet

Non-essential AA (NEAA)

 Made by humans
 Tyrosine is misclassified as formed from phenylalanine and, therefore is an essential AA
- Previous lecture mention phenylalanine/tyrosine catabolism

LO2. COMMON INTERMIDIATES USED TO BIOSYNTHEIS AA

NEAA come from 4 common intermediates precursors

1. Pyruvate
2. Oxaloacetate Associated with the citric acid cycle
3. Α-ketoglutarate
4. 3-phosphoglycerate
Associated with glycolysis
Examples

 Use of transamination
- Pyruvate => alanine
- oxaloacetate => aspartate => asparagine
- α-ketoglutarate => glutamate => glutamine Secondary transamination process on a side chain
transamination Process (reminder)

 remove amide group from 1 AA
 form α-ketoacid
 place amide group on another α-ketoacid
 form another AA
 occur on the main chain as well as on the side chains (Asn, Gln)

LO3. THE BIOSYNTHESIS OF PROLINE & ORNITHINE VIA 2 DIFFERENT PATHWAYS

The glutamate family

 glutamine
 proline
 arginine
 (ornithine)

Glutamate to proline

 4 steps

,  Glutamate => glutamate-5-phosphate => glutamate-5-semialdehyde => Δ’- Pyrroline-5-carboxylate => proline




From glutamate to glutamate-5-semiphosphate

 Phosphorylation to get activation
 Followed by reduction reaction

Key points:

 Glutamate-5-phosphate is
- Unstable as extremely reactive
- Therefore, not seen only implied to be there
 A multi-enzyme system carried out this process
- The multi-enzymes keeps the highly reactive intermediate away from the environment and within the
enzyme structure.

Glutamate to ornithine

 3 steps
 Get to glutamate-5-semialdehyde and from their branch to ornithine
 Or in glutamate to arginine

Glutamate to arginine

 5 steps then urea cycle
 Glutamate => N-Acetylglutamate => N-Acetylglutamate-5-phosphate => N-Acetylglutamate-5-semialdehyde => N-
acetylornithine => ornithine => (urea cycle) => arginine
- Ornithine has come from outside the urea cycle thus the process increases the concentration of ornithine
 Take home message:
- metabolic pathways in the body are able to produce the same molecules via different means
- Simple processes have created ornithine by different routes
Urea cycle
Glutamate to ornithine

3-phosphoglycerate

 Members of 3-phosphoglycerate family
- Serine
- Cysteine
- Glycine
 To serine, 3 steps
1. oxidation step
2. Transamination step
3. Hydrolysis step