BIOCHEMISTRY

SGD: Amino acid metabolism

1. Genetic deficiency in an enzyme involved in the catabolism of an amino acid typically (but not always, e.g
nonketotic hyperglycinemia) results in ketoacidosis. Ketoacidosis always happens with hereditary deficiencies
of branched-chain amino acid metabolism. Why does this always happen with branch chain amino acid
metabolism?
Answer: The most common enzyme deficient in deficiencies of branched-chain amino acid
metabolism is branched-chain alpha-ketoacid dehydrogenase that allows conversion of alpha ketoacids to three different CoA derivatives. When this enzyme is deficient, conversion to the derivatives
would not proceed that therefore allow abnormal accumulation of the alpha-ketoacid precursors. This
results to the condition Maple Syrup Urine Disease characterized with symptoms of ketoacidosis,
mental retardation, and burnt odor of urine.

2. People with hereditary deficiency in ornithine transcarbamoylase activity develop hyperammonemia. One
component of the treatment for this is dietary supplementation with citrulline. Indicate the metabolites on the
shortest pathway from ammonia to urea in individuals lacking ornithine transcarbamoylase activity but
supplemented with citrulline. Indicate the pathway order using arrows to connect the metabolites in your
answer.
Answer:

3. Pathway of Carbon and Nitrogen in Glutamate Metabolism. When glutamate undergoes oxidative degradation
in the liver of the rat, in which atoms of the following metabolites will each isotope be found?
a. Urea
d. Citrulline
b. Succinate
e. Ornithine
c. Arginine
f. Aspartate

4.

a.

b.

c.

5.

a.

a.
Amino groups of urea will contain 15N, a result of
glutamate dehydrogenase producing 15NH+4 or a transaminase producing 15N-labeled aspartate.
b.
After loss of the amino group, the [2-14C] alphaketoglutarate will be metabolized in the citric acid cycle. Succinate thus formed will be labeled in the
carboxyl groups.
c.
The arginine formed in the urea cycle will contain 15N in
both guanidine nitrogen.
d.
Citrulline formed in the urea cycle will contain 15N in the
carboxamide group.
e.
No labeled N will be found in ornithine.
f.
Aspartate will contain 15N in its amino group as a result of
transamination from glutamate. It will also contain 14C in its carboxyl groups as a result of succinate
conversion to oxaloacetate. In c, d, e: intermediates in the urea cycle will contain low levels of 14C
as a result of a very weak synthesis of ornithine from glutamate.
g.
Ammonia Intoxication Resulting from an Arginine- Deficient Diet. In a study conducted some years ago, cats
were fasted overnight then given a single meal complete in all amino acids except arginine. Within two hours,
blood ammonia levels increased from a normal level of 18ug/L to 140 ug/L, and the cats showed symptoms of
ammonia toxicity. A control group fed a complete amino acid diet or an amino acid diet in which arginine was
replaced by ornithine showed no unusual clinical symptoms.
What was the role of fasting?

The fasting resulted in lowering of blood glucose levels.

Subsequent feeding of an arginine free diet led to a rapid catabolism of all the amino acids.
Especially the glucogenic ones. This catabolism was worsened by the lack of essential amino acids
which prevented protein synthesis.
a.
What caused to ammonia levels to rise in the experimental group? Why did the absence of arginine led to
ammonia toxicity? Is arginine an essential amino acid in cats? Why or why not?

Oxidative deamination of amino acids caused the elevation of

ammonia levels. The lack of arginine slowed the conversion of ammonia to urea. Arginine synthesis
in cats is not sufficient to meet the needs imposed by the stress of the experiment, which suggests
that arginine is an essential amino acid.
a.
Why can ornithine be substituted for arginine?

Ornithine can be substituted for arginine because it also has an

intermediate in the urea cycle.
a.
b.
The Case Against Liquid Protein Diet. A weight reducing diet heavily promoted some years ago required the
daily intake of liquid protein (soup of hydrolyzed gelatin), water and an assortment of vitamins. All other food
and drink were to be avoided. People on this diet typically lost 10-14lb in the first week.
Opponents argued that the weight loss was almost entirely due to water loss and would regain almost
immediately when a normal diet was resumed. What is the biochemical basis for this argument?
a. A person on a diet consisting only of protein must use amino acids as the principal source of
metabolic fuel. Because the catabolism of amino acids requires the removal of nitrogen as urea, the
process consumes large quantities of water to dilute and excrete the urea in the urine. Furthermore,
electrolytes in the liquid protein must be diluted with water and excreted. If this abnormally large
daily water loss through the kidney is not balanced by a sufficient water intake, a net loss of body
water results.

b. A number of people on this diet died. What are some of the dangers inherent in the diet and how can they lead
to death?
a. When considering the nutritional benefits of protein, keep in mind the total amount of amino
acids needed for protein synthesis and the distribution of amino acids in the dietary protein. Gelatin
contains a nutritionally unbalanced distribution of amino acids. As large amounts of gelatin are
ingested and the excess amino acids are catabolized, the capacity of the urea cycle may be
exceeded, leading to ammonia toxicity. This is further complicated by the dehydration that may
result from excretion of large quantities of urea. A combination of these two factors could produce
coma and death.
b.
c.