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Bioc 460 Spring 1999
Lecture 38 - Chapter 25
- Overview
of amino acid degradation
- The Urea cycle
- Glucogenic and ketogenic amino acids
- Genetic defects in amino acid metabolism
Overview
of amino acid degradation
Amino acids in excess of those required for protein synthesis cannot be stored and they must be metabolized to release NH4 and carbon skeletons. High levels of nitrogen are toxic, excretion therefore is a crucial metabolic process. In terrestrial vertebrates nitrogen is excreted as urea, birds excrete uric acid, and fish excrete NH4 directly into water.
The major site of amino acid degradation in mammals is the liver (surprise, surprise). Aminotransferases are enzymes that transfer the amino group from amino acids to keto acids. One of the most important enzymes in amino acid metabolism is glutamate dehydrogenase because it uses oxidative deamination to produce NH4 and alpha ketoglutarate from glutamate.
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The combined activity of these two enzymes results in deamination of amino acids to produce NH4.
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The carbon skeletons of most amino acids can be converted to metabolic intermediates.
Figure 25.10
The Urea Cycle
In terrestrial vertebrates, urea is synthesized in the liver by the urea cycle, a biochemical pathway discovered by Hans Krebs five years before he discovered the citric acid cycle (a.k.a. the Krebs cycle). One of the N atoms is from NH4 (via carbamoyl phosphate) and the other is from aspartate. Some of the Urea cycle reactions take place in the mitochondrial matrix, while others occur in the cytosol.
The net reaction for the synthesis of urea is:
CO2 + NH4 + 3 ATP + aspartate + 2 H2O ---> urea + 2 ADP + 2 Pi + AMP + PPi + fumarate
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Figure 25.6
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The urea cycle is linked to the citric acid cycle through the shared intermediate fumarate.
Figure 25.7
Glucogenic
and ketogenic amino acids
The strategy of amino acid degradation is to form major metabolic intermediates that can be converted into glucose or be oxidized by the citric acid cycle. The carbon skeletons of all 20 amino acids can be converted into one of 7 intermediates and are referred to as glucogenic or ketogenic amino acids based on these metabolic products.
Glucogenic amino acids form:
- pyruvate
- a-ketoglutarate
- succinyl CoA
- fumarate
- oxaloacetate
Ketogenic amino acids form:
- acetyl CoA
- acetoacetyl CoA
Figure 25.10 (again)
Figure 25.11, Figure 25.12
Figure 25.14, Figure 25.15
Genetic
defects in amino acid metabolism
Inherited defects in the urea cycle cause hyperammonemia and brain damage
Figure 25.8
Figure 25.9
A block in the hydroxylation of phenylalanine can lead to severe mental retardation. The disease is called phenylketonuria (PKU) and it is due to the build-up of phenylalanine and phenylpyruvate as a result of a deficiency in the enzyme phenylalanine hydroxylase. Early diagnosis of PKU is essential and the effects of the disease can be largely eliminated by strictly controlling the amount of phenylalanine in the diet.
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Figure 25.23
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Figure 25.25
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Department of Biochemistry http://www.biochem.arizona.edu/classes/bioc460/spring/springindex.html
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