Lecture 4 (2B) - Amino Acid Biosynthesis

Question 1

Many amino acids are not made by humans

(only plants and microorganisms)

Answer 1

known as essential amino acids

Question 2

Nonessential amino acids

Answer 2

made by humans

Question 3

Tyrosine “misclassified”

Answer 3

• from phenylalanine that’s essential
• disease of last lecture (alkaptonuria, phenylketonuria)
• can’t make it if no phenylalanine comes from outside

Question 4

Other than the urea cycle, arginine

Answer 4

from outside

Question 5

Nonessential amino acids come from 4 common intermediates

Answer 5

• pyruvate
• oxaloacetate
• α-ketoglutarate

(associated with citric acid cycle)

• 3-phosphoglycerate

(glycolysis - toward citric acid cycle but not associated)

Question 6

Use of transamination

Answer 6

• pyruvate (ketone) → alanine (amino acid)
• oxaloacetate (ketone) → aspartate → asparagine
• α-ketoglutarate (ketone) → glutamate → glutamine

Question 7

Process of transamination

Answer 7

• 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

Question 8

Citric acid metabolisms

Answer 8

catabolism of amino acids (to make others)

biosynthesis of other small molecules

Question 9

GLUTAMATE to PROLINE

4 steps

Answer 9

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)

Question 10

GLUTAMATE to PROLINE

key points

Answer 10

• glutamate-5-phosphate is unstable
  
  • not seen, only implied
• multi-enzyme system
• kept within structure

Question 11

GLUTAMATE to ORNITHINE

3 steps

Answer 11

• get to glutamate-5(γ)-semialdehyde (2 steps through intermediate)
• from there branch to ornithine

OR

GLUTAMATE to ARGININE

Question 12

GLUTAMATE to ARGININE

5 steps then urea cycle

Answer 12

glutamate

→

N-acetylglutamate

(in control of urea cycle)

(activation)

→

N-acetylglutamate-5-phosphate

→

N-acetylglutamate-5-semialdehyde

→

N-acetylornithine

→

ornithine

→

urea cycle

→

arginine

Question 13

3-phosphoglycerate

Answer 13

forms:

• serine
• cysteine
• glycine

Question 14

_3-PHOSPHOGLYCERATE _to GLYCINE

Answer 14

• 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

Question 15

Essential amino acids

Answer 15

• the aspartate family
• the pyruvate family
• the aromatic amino acids

Question 16

Essential amino acids

the Aspartate family

Answer 16

• lysine
• methionine
• threonine

Question 17

Essential amino acids

the Pyruvate family

Answer 17

• leucine
• isoleucine
• valine
• valine and isoleucine have same pathways EXCEPT for the first step
• leucine from valine pathway

Question 18

Essential amino acids

aromatic amino acids

Answer 18

• phenylalanine
• tyrosine
• tryptophan
• all have common precursor - CHORISMATE

Question 19

CHORISMATE

to

PHENYLALANINE and TYROSINE

Answer 19

• 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

Question 20

CHORISMATE

(prephenate)

to

TYROSINE

Answer 20

prephenate → tyrosine

• through 4-hydroxyplenylpyruvate
• oxidation/reduction + decaroxylation (keep hydroxyl) → transamination

Question 21

CHORISMATE

(prephenate)

to

PHENYLALANINE

Answer 21

prephenate → phenylalanine

• through phenylpyruvate
• decarboxylation (lose hydroxyl) → transamination

Question 22

CHORISMATE

to

TRYPTOPHAN

Answer 22

• 6 step process by tryptophan synthase
  
  • must channel molecules through sites to ensure it doesn’t drift off for something else

1. removing pyruvate, adding amide
2. adding a sugar
3. sugar ring cleavage
4. new ring fromed
5. indole formed

• indole ring very reactive
• precursor to sidechain of tryptophan

6. serine added
   * to make main chain carbons (like cysteine)

→ tryptophan formed

Question 23

Diseases

Answer 23

most concerned with catabolism (breakdown) of amino acids

Question 24

Disease

L-serine deficiency

Answer 24

• 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

Question 25

3-phosphoglycerate to…

(picture)

Answer 25

Question 26

α-ketoglutarate to

(picture)

Answer 26

Question 27

Basic set of 20 amino acids

(picture)

Answer 27

Question 28

Fates of the carbon skeletons of the amino acids

(picture)

Answer 28

Question 29

Oxaloacetate to…

(picture)

Answer 29

Question 30

Pyruvate to…

(picture - red cross = we don’t make)

Answer 30