protein metabolism

• Protein digestion and absorption

  Digestion of proteins involves the hydrolysis of the peptide bonds that link amino acids to each other. This process begins in the stomach and is completed in the small intestine. The amino acids released by digestion are absorbed through the intestinal wall into the bloodstream.

  
• Amino acid pool


  The total supply of free amino acids available for use in the human body. It is derived from dietary protein, protein turnover, and biosynthesis of non-essential amino acids in the liver.

  
• Amino acid utilization


  Amino acids from the amino acid pool are used for protein synthesis, synthesis of nonprotein nitrogen compounds, synthesis of nonessential amino acids, and energy production.

  
• Transamination


  An enzyme-catalyzed transfer of an amino group from an α-amino acid to an α-keto acid. It is a step in obtaining energy from amino acids.

  
• Oxidative deamination


  A reaction in which an α-amino acid is converted into an α-keto acid, accompanied by the release of a free ammonium ion. It is a step in obtaining energy from amino acids.

  
• Urea cycle


  The metabolic pathway that converts ammonium ions and aspartate into urea. This cycle processes the ammonium ions in the form of carbamoyl phosphate, a compound formed from CO2, NH4+, ATP, and H2O.

  
• Amino acid carbon skeletons

  Classified as glucogenic or ketogenic on the basis of their catabolic pathways. Glucogenic amino acids are degraded to intermediates of the citric acid cycle and can be used for glucose synthesis. Ketogenic amino acids are degraded into acetoacetyl CoA or acetyl CoA and can be used to make ketone bodies.

  
• Amino acid biosynthesis


  The process in which the body synthesizes amino acids from intermediates of the glycolysis pathway and the citric acid cycle. Ten amino acids can be synthesized by the body, the other ten are essential amino acids that must be obtained from the diet.

  
• Hemoglobin catabolism


  Hemoglobin from red blood cells undergoes a stepwise degradation to biliverdin, to bilirubin, and then to bile pigments that are excreted from the body.
• The state that results when the amount of nitrogen taken into the human body as protein equals the amount of nitrogen excreted from the body in waste materials is called nitrogen balance.
• Negative nitrogen imbalance occurs when protein degradation exceeds protein synthesis, resulting in tissue wasting. Positive nitrogen imbalance occurs when the rate of protein synthesis (anabolism) is more than protein degradation (catabolism), resulting in large amounts of tissue synthesis, as during growth or pregnancy.
• Protein digestion


  Starts in the stomach where gastric acidity denatures protein, activates pepsin, and kills most bacteria. Large polypeptide chains then pass into the small intestine where pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase) further hydrolyze proteins to smaller peptides, which are then broken down to amino acids by intestinal enzymes and absorbed into the bloodstream.

  
• The amino acid pool is derived from dietary protein, protein turnover, and biosynthesis of non-essential amino acids in the liver.

  
• Ways amino acids from the amino acid pool are used

  • Protein synthesis
  • Synthesis of non-protein nitrogen-containing compounds
  • Synthesis of nonessential amino acids
  • Production of energy

  
• Amino acid degradation


  Involves two stages: removal of the α-amino group and degradation of the remaining carbon skeleton. The amino nitrogen is converted to ammonium ion and ultimately excreted as urea, while the carbon skeleton is converted to pyruvate, acetyl CoA, or a citric acid cycle intermediate.

  
• Transamination


  An enzyme-catalyzed process in which the amino group of an α-amino acid is transferred to an α-keto acid. The coenzyme pyridoxal phosphate (vitamin B6) is an essential part of the active site of transaminases.

  
• Oxidative deamination


  An amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia, which then enters the urea cycle.

  
• Removal of the amine functional group

  1. Ammonia is released

  2. Ammonia eventually goes into the urea cycle
• Transamination


  The body can manufacture the amino acids that it needs
• Transaminases


  • An essential part of the active site is pyridoxal phosphate (PLP), the coenzyme form of Vit B6
• Oxidative deamination is a catabolic reaction whereby the α-amino group of an amino acid is removed, forming an α-keto acid and ammonia

  
• Oxidative deamination


  • Occurs primarily in the liver and the kidneys through the activity of the enzyme amino acid oxidase
  • Two amino acids, serine and threonine, undergo direct deamination by dehydration-hydration process rather than oxidative deamination
• The urea cycle


  1. Ammonium ion produced by oxidative deamination is converted to carbomyl phosphate and then to urea

  2. Arginine, citrulline, and ornithine are involved

  3. Urea is picked up by the blood from the liver and carried to the kidneys for excretion

  4. Urea is the principal end product of protein metabolism and contains a large percentage of the total nitrogen excreted by the body

  5. Failure of any part of this cycle leads to an accumulation of ammonia with severe retardation or death

  
• Stages of the urea cycle

  1. Carbamoyl group transfer: Carbamoyl group of carbamoyl phosphate is transferred to ornithine to form citrulline

  2. Citrulline-aspartate condensation: Citrulline reacts with aspartate to produce argininosuccinate utilizing ATP

  3. Argininosuccinate cleavage: Argininosuccinate is cleaved to arginine and fumarate

  4. Hydrolysis of urea from arginine: Hydrolysis of arginine produces urea and regenerates ornithine

  
• Degradation products of amino acid carbon skeletons

  • Pyruvate
  • Acetyl CoA
  • Acetoacetyl CoA
  • Alpha-ketoglutarate
  • Succinyl CoA
  • Fumarate
  • Oxaloacetate

  
• Glucogenic amino acid


  An amino acid that has a carbon-containing degradation product that can be used to produce glucose via gluconeogenesis

  
• Ketogenic amino acid


  An amino acid that has a carbon-containing degradation product that can be used to produce ketone bodies

  
• Types of amino acids

  • Purely ketogenic: Leu & Lys
  • Both glucogenic and ketogenic: Those degraded to pyruvate, as well as Tyr, Phe, & Ile
  • Purely glucogenic: Remaining 9 amino acids

  
• Red blood cells (RBCs)

  • Highly specialized cells whose primary function is to deliver oxygen to cells and remove carbon dioxide from body tissues
  • Mature RBCs have no nucleus or DNA, filled with red pigment hemoglobin
  • RBCs are formed in the bone marrow, with ~200 billion new ones formed daily
  • The life span of a red blood cell is about 4 months
  • Old RBCs are broken down in the spleen (primary site) and liver (secondary site)
• Degradation of hemoglobin


  1. Globin protein part is converted to amino acids and put in amino acid pool

  2. Fe atom becomes part of ferritin, an iron storage protein

  3. The heme (tetrapyrrole) is degraded to bile pigments and eliminated in feces or urine

  
• Bile pigments


  • Biliverdin - green in color
  • Bilirubin - reddish orange in color
  • Stercobilin - brownish in color (gives feces their characteristic brown color)
  • Urobilin - yellow in color and present in urine (gives characteristic yellow color to urine)
• Jaundice


  Results from liver, spleen and gallbladder malfunction, causing higher than normal bilirubin levels in the blood and giving the skin and white of the eye yellow tint
• Feasting (over eating)


  Causes the body to store a limited amount as glycogen and the rest as fat
• Fasting (no food ingestion)


  The body uses its stored glycogen and fat for energy
• Starvation (not eating for a prolonged period)

  Glycogen stores are depleted, body protein is broken down to amino acids to synthesize glucose, fats are converted to ketone bodies