Chapter Introduction

Protein Turnover and Amino Acid Catabolism

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This fourteenth-century hand-colored woodcut from Germany depicts a wheel that classifies urine samples according to their color and consistency. In the middle of the wheel, a doctor inspects a patient’s urine by sight, smell, and taste. The vials on the wheel aided physicians in diagnosing diseases. A key component of urine is urea, which is formed from the amino groups released during the metabolism of amino acids.
[(Left) Rosenwald Collection. Rare Book and Special Collections Division, Library of Congress (128.2).]

OUTLINE

  1. Proteins Are Degraded to Amino Acids

  2. Protein Turnover Is Tightly Regulated

  3. The First Step in Amino Acid Degradation Is the Removal of Nitrogen

  4. Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates

  5. Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates

  6. Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation

The digestion of dietary proteins in the intestine and the degradation of proteins within the cell provide a steady supply of amino acids to the cell. Many cellular proteins are constantly degraded and resynthesized in response to changing metabolic demands. Others are misfolded or become damaged and they, too, must be degraded. Unneeded or damaged proteins are marked for destruction by the covalent attachment of chains of a small protein called ubiquitin and then degraded by a large, ATP-dependent complex called the proteasome. The primary use of amino acids provided through degradation or digestion is as building blocks for the synthesis of proteins and other nitrogenous compounds such as nucleotide bases.

Amino acids in excess of those needed for biosynthesis can neither be stored, in contrast with fatty acids and glucose, nor excreted. Rather, surplus amino acids are used as metabolic fuel. The α-amino group is removed, and the resulting carbon skeleton is converted into a major metabolic intermediate. Most of the amino groups harvested from surplus amino acids are converted into urea through the urea cycle, and their carbon skeletons are transformed into acetyl CoA, acetoacetyl CoA, pyruvate, or one of the intermediates of the citric acid cycle. The carbon skeletons are converted into glucose, glycogen, and fats.

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Several coenzymes play key roles in amino acid degradation; foremost among them is pyridoxal phosphate. This coenzyme forms Schiff-base intermediates, which are a type of aldimine, that allow α-amino groups to be shuttled between amino acids and ketoacids. We will consider several genetic errors of amino acid degradation that lead to brain damage and mental retardation unless remedial action is initiated soon after birth. The study of amino acid metabolism is especially rewarding because it is rich in connections between basic biochemistry and clinical medicine.