Transcript Amino Acids: From Ingestion To Excretion.

Amino Acids: From
Ingestion To Excretion.
An introduction to the
degradation of proteins into
amino acids and the production
of urea in the liver.
Overview
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In humans, amino acids can be synthesized
(non-essential) or must be obtained through
the diet (essential).
Most amino acids are obtained through diet
and are metabolized in the liver by
transamination.
Amino acids are catabolized in to its α-Keto
acid and ammonia (NH4+).
Excess NH4+ is converted by the liver to
urea and excreted.
Amino acids are obtained by ingestion of protein
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Ingestion of protein stimulates the secretion
of hydrochloric acid (HCl) and pepsinogen by
gastric glands in the stomach lining.
Pepsinogen is an inactive enzyme (a
zymogen) that is activated into pepsin by the
low pH of the HCl secreted.
Pepsin hydrolyzes the ingested protein on the
amino side at cleavage points (the residue
adjacent to the cleavage point) Phe, Trp, and
Tyr.
Other amino acids are cleaved by enzymes secreted from the pancreas
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Release of the low pH stomach contents into the
small intestine triggers hormones that stimulate the
pancreas to secrete bicarbonate into the small
intestine to neutralize the pH to about pH 7.
Zymogens trypsinogen, chymotrypsinogen, and
procarboxypeptidase are also secreted by the
pancreas and activated by other enzymes, like
enteropeptidase.
These activated enzymes further hydrolyze the
incoming peptides from the stomach.
Other enzymes in the small intestine complete the
degradation of the ingested proteins into their free
amino acids that can then travel through the
capillaries, into the blood, and travel to the liver.
Oxidative degradation of amino acids in the liver
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Oxidative degradation of amino acids removes the α-amino groups.
The removal of α-amino groups are done by enzymes called
transaminases.
Transaminases promote transamination reactions where the α-amino
reacts with α-Ketoglutarate to form L-Glutamate and the
corresponding α-Keto acid.
All the amino groups from the amino acids are collected by αKetoglutarate and converted to L-Glutamate.
All of these reactions require a prosthetic group – Vitamin B6.
Vitamin B6 stabilizes the carbanion formed during transamination.
Glutamate and the transportation of collected amino groups
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Glutamate is important in the transportation of
collected amino groups.
Glutamate travels to the mitochondria of the liver
where it goes through oxidative deamination.
The deamination is catalyzed by L-Glutamate
dehydrogenase in the mitochondria.
Transport of ammonia
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Ammonia is toxic to animals.
In humans, ammonia is converted to a less toxic
substance in tissues other than the liver.
In these tissues, ammonia is enzymatically attached
to glutamate to create glutamine.
This process is done by the enzyme glutamine
synthetase.
Glutamine is nontoxic and can pass through
membranes and into the blood to be transported into
the liver.
Conversion of glutamine
Just as glutamine is converted to α-Ketoglutarate
and NH4+ in the liver, glutamine is converted by
glutaminase to give off glutamate and NH4+.
Conversion of ammonia
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Both processes give off NH4+ in the liver.
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This NH4+ is converted to a less harmful
substance for excretion.
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The mitochondria in the liver converts NH4+ to
urea in the urea cycle.
The urea can then travel safely out of the liver
into the blood.
The urea travels to the kidneys where it is
excreted into the urine.
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References
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Slide 2: Lehninger, A. Short course in Biochemistry, Worth
Publishers: New York, NY, 1973, pp. 321 – 325.
Lehninger, A.; Nelson, D.; Cox, M. Principles of Biochemistry, 2nd
ed., Worth Publishers: New York, NY, 1993, pp. 506 – 507, 511,
515.
Slides 3 – 4: ibid., pp. 150 – 151, 507 – 510.
Slide 5: ibid., pp. 511 – 512.
Slide 6: ibid., pp. 511, 514 – 515.
Slide 7: ibid., pp. 515 – 517.
Slide 8: ibid., p. 515.
Slide 9: ibid., pp. 511, 515 – 517.