Amino Acids: From Ingestion To Excretion.

1. Amino Acids: From Ingestion To Excretion. An introduction to the degradation of proteins into amino acids and the production of urea in the liver.

2. Overview • 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.

3. Amino acids are obtained by ingestion of protein • 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.

4. Other amino acids are cleaved by enzymes secreted from the pancreas • 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.

5. Oxidative degradation of amino acids in the liver • 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 α-Ketoglutarate and converted to L-Glutamate. • All of these reactions require a prosthetic group – Vitamin B6. • Vitamin B6 stabilizes the carbanion formed during transamination.

6. Glutamate and the transportation of collected amino groups • 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 byL-Glutamate dehydrogenase in the mitochondria.

7. Transport of ammonia • 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.

8. 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 andNH4+.

9. Conversion of ammonia • Both processes give off NH4+ in the liver. • This NH4+ is converted to a less harmful substance for excretion. • 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.

10. References • 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.