Amino Acid Catabolism
C483 Spring 2013
1. Which of the following is/are true statement(s) about glutamine and alanine?
A) They are nitrogen donors in many biosynthetic reactions.
B) They are part of the urea cycle.
C) They carries nitrogen between tissues, thus avoiding high toxic levels of NH4+ in
blood.
D) In mammal liver, they receive net nitrogen from glutamate in transaminations.
2. What would be the product of the transamination of the structure shown below?
(The unionized forms are shown.)
3. ATP is required to degrade many proteins because it is required to
A) form the proteosome.
B) attach ubiquitin to the target protein.
C) hydrolyze a ubiquitinated protein.
D) All of the above.
4. The enzyme ________ is one of the most abundant in liver mitochondria and
catalyzes the synthesis of the molecule shown below.
A) arginase
B) carbamoyl phosphate synthetase I
C) 4-α-carbinolamine dehydratase
D) transaminase
5. Which of the following is false concerning the urea cycle?
A) Ornithine acts catalytically in the urea cycle.
B) Metabolic disease can result from lack of urea cycle enzymes.
C) The four reactions of the cycle take place in the liver mitrochondrial matrix.
D) One molecule of urea is produced at the cost of 4 ATP equivalents.
Overview
• Protein Turnover
• Amino Acid Catabolism
– Nitrogen pathways
– Carbon backbone
• From perspective of
human metabolism
Juicy Steak Part 2
Digestion
Protein Degradation
• All proteins have
a “half-life”
• Part of
regulation
• Also important
in misformed/
mutant proteins
• Ubituitin
Marked for destruction
• Complex system guards
against marking “good”
proteins
• Costs ATP
• Proteasome
– Nucleophile hidden in barrel
Amino Acid Degradation
• Nitrogen processing is the first step
• Then carbon chain is metabolized
• Example:
• Two nitrogen transfer reactions
Reaction1: Transamination
• All amino acids shuttle their nitrogen toward
glutamate
Transamination
• Not an overall Redox reaction
• Requires PLP
Reaction 2: Oxidative Deamination
• What happens to all the glutamate?
• Glutamate Dehydrogenase
Nitrogen Processing on Tissue Level
• The alanine-glucose cycle
Amino
Acids
Nitrogen Processing on Tissue Level
• Glutamine can act as
– Ammonia transporter (like alanine)
– Substrate in biosynthesis requiring amino groups
Role of Liver Mitochondia
• Sequester toxic ammonia
• Make less toxic, execrable form
• Urea Cycle
Carbamoyl phosphate
• Cost of 2 ATP
– Phosphate leaving group
• Activation of ammonia for
– Excretion
– biosynthesis
Chemistry of Urea Cycle
• Catalytic
ornithine
+ ATP
+ AMP
• Fumarate
• Urea = 4 ATP
Solving Metabolic Problems
• Arginosuccinase deficiency
• Low protein diet
– Minimize ammonium
excreted
• High arginine diet
– Provide carrier
X
Urea Cycle: Compartmentalization
• Ammonia locked
into matrix
• Urea released
• Uses glutamate/
aspartate shuttle
Summary: Main Players
• Glutamate: receives nitrogen from AA, then
ammonia is released in liver mitochondria
• Glutamine: ammonia transport; biosynthesis
• Alanine: ammonia transport
• Aspartate: nitrogen donor to urea
• Arginine: urea cycle
Answers
1.
2.
3.
4.
5.
C
III
D
B
C