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Chapter 18
Amino Acid Oxidation and the
Production of Urea
Amino Acid Oxidation, Production of Urea
Key topics: To Know
– How proteins are digested in animals
– How amino acids are degraded in animals as a
source of energy
– How urea is made and excreted
– Some genetic defects in amino acid recycling
The use of amino acids as fuel
varies greatly by organism
• About 90% of energy needs of carnivores can be met
by amino acids immediately after a meal
• Microorganisms scavenge amino acids from their
environment for fuel when needed
• Only a small fraction of energy needs of herbivores
are met by amino acids
• Plants do not use amino acids as a fuel source, but
can degrade amino acids to form other metabolites
Metabolic Circumstances of Amino Acid
Oxidation
• Leftover amino acids from normal protein turnover
• Dietary amino acids that exceed body’s protein
synthesis needs
• Proteins in the body can be broken down to supply
amino acids for energy when carbohydrates and
fats are scarce (starvation, diabetes mellitus)
Overview
Proteosome Function
Core
Proteasome
Ubiquitin Binding Sites top and bottom
Nature 445:618 Feb 8, 2007
Ubiquitin Targeting a
Cytoplasmic Protein
5th Edition: See pages 11071109, Fig 27-47, -48
6th Edition: See pages 11471149, Fig 27-47, -48.
Protein Amino Terminal-aa Determines
Protein’s Half-life
stabilizing
M, G, A, S, T, V
>20 hrs
destabilizing
I, N, Y, D, P, L, F, D, K, R
30 – 2 min
Nitrogen Delivered to Liver Cells
Nitrogen Excretion Forms
Transaminases
EOC Problem 1 a
Transamination
Problem.
PLP – Transaminase Cofactor
Transaminases Used in Diagnosis of Tissue
Damage
Tissue damage  leaks enzymes into blood
(S)GPT: glutamate-pyruvate transaminase
(S)GOT: glutamate-oxaloacetate transaminase
-- indicate probable liver damage (toxins,
infections)
(S)CK: creatine kinase
-- heart damage  heart attack, infection
S for “serum”
EOC Problem 2: Measuring transaminases in blood –
coupled reactions! (to things you already know)
Glutamate Dehydrogenase
Glutamine
Synthetase
This is just one
reaction:
Glutamine
Synthetase
GlucoseAlanine Cycle is
in Muscle Only
EOC Problem 3:
Alanine and
Glutamine in Blood.
Urea Cycle
Overview
Amino acids come
from recycling
(glutamine), muscle
glycolysis (alanine),
and diet.
Begin in the Mitochondrion
Mechanims of the Two Nitrogen Entry Points in
Urea Cycle
Relationship to Citric Acid Cycle
EOC Problem 4:
Alanine and Lactate
have identical oxidstate, why do cells
get less energy
from alanine?
EOC Problem 8:
Asp Transaminase
activitiy.
Urea Cycle Controlled Acetyl-Glutamate
Acetyl-Glu is in the Arg
synthetic pathway in
bacteria and plants, in
animals it is only
regulatory
Benzoate and
Phenylbutyrate Given
to Lower Blood
Ammonium
Treatment for genetic
defects in Urea Cycle
Excreted in Urine
Summary of Amino Acid Catabolism
1 Carbon Transfer Cofactors
Pyruvate Family
Glycine Degradation in Kidney
1. D-amino acid oxidase breaks down D-aa’s from
bacterial peptidoglycan.
2. Oxalate-Ca++ are major substance in kidney stones.
Acetyl-SCoA
Family
Other Uses of W’s Indole Ring
Phenylalanine
Degradation
PKU = Phenylketouria
EOC Problem 11:
Analysis of blood and
PKU
α-KetoGlutarate Family
Succinyl-SCoA
Family
Oxaloacetate
Family
Amino Acid Carbon Use
Things to Know and Do Before Class
1. Amino acids from protein are an important energy source
in carnivorous animals and during starvation.
2. The first step of AA catabolism is transfer of the NH3 via
PLP-dependent aminotransferase usually to ketoglutarate to yield L-glutamate.
3. In most mammals, toxic ammonia is quickly converted to
carbamoyl phosphate and passed into the urea cycle
4. Amino acids are degraded to pyruvate, acetyl-CoA, αketoglutarate, succinyl-CoA, and/or oxaloacetate
5. Amino acids yielding acetyl-CoA are ketogenic.
6. Amino acids yielding other end products are glucogenic.
7. Genetic defects in amino degradation pathways result in a
number of human diseases: our example is PKU.
8. EOC Problems 1-5, 8, 11.