Protein Metabolism

• Nitrogen Balance

  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
• Negative nitrogen imbalance: Protein degradation exceeds protein synthesis.

  Amount of nitrogen in urine exceeds nitrogen consumed.

  Results in tissue wasting.
• Positive nitrogen imbalance: Rate of protein synthesis (anabolism) is more than protein degradation (catabolism)

  Results in large amounts of tissue synthesis.

  During growth, pregnancy, etc.
• Protein digestion (denaturation and hydrolysis) starts in the stomach
• Dietary protein in stomach promotes release of Gastrin hormone which promotes secretion of pepsinogen and HCl
• HCl in stomach has 3 functions:

  Gastric acidity denatures protein thereby exposing peptide bonds.

  Gastric acidity (pH of 1.5-2.0) kills most bacteria.

  Activates pepsinogen (inactive) to pepsin (active).
• Enzyme pepsin hydrolyzes about 10% peptide bonds.
• Large polypeptide chains pass from stomach into small intestine:
• Enzymes (Trypsin, chymotrypsin carboxypeptidase , and aminopeptidase) are produced in inactive forms called zymogens and are activated at their site of action
• fill in the blank

  A) dietary protein

  B) mouth

  C) saliva

  D) stomach

  E) HCI

  F) pepsin

  G) large polypeptides

  H) trypsin

  I) chymotrypsin

  J) carbosypeptidase

  K) aminopeptidase

  L) small intestine

  M) amino acid

  N) active transport

  O) intestinal lining

  P) amino acids in bloodstream

  
• Amino acid pool

  -Amino acids formed through digestion process enters the amino acid pool in the body:

  -Amino acid pool: the total supply of free amino acids available for use in the human body
• The amino acid pool is derived from 3 sources:

  – Dietary protein

  – Protein turnover: A repetitive process in which the body proteins are degraded and resynthesized

  – Biosynthesis of amino acids in the liver. only non-essential amino acids are synthesized
• Protein synthesis: • About 75% of amino acids go into synthesis of proteins that is needed continuous replacement of old tissues (protein turnover) and to build new tissues (growth).
• Synthesis of non-protein nitrogen-containing compounds: • Synthesis of purines and pyrimidines for nucleic acid synthesis . • Synthesis of heme for hemoglobin, neurotransmitters and hormones
• Synthesis of nonessential amino acids: • Essential amino acids can’t be synthesized because of the lack of appropriate carbon chain.
• Production of energy • Amino acids are not stored in the body, so the excess is degraded. • Each amino acid has a different degradation pathway.
• Degradation of an amino acid takes place in two stages: ̶

  The removal of the -amino group and

  The degradation of the remaining carbon skeleton
• The amino nitrogen atom is removed and converted to ammonium ion, which ultimately is excreted from the body as urea.
• The remaining carbon skeleton is then converted to pyruvate, acetyl CoA, or a citric acid cycle intermediate, depending on its makeup, with the resulting energy production or energy storage
• The remaining carbon skeleton is then converted to pyruvate, acetyl CoA, or a citric acid cycle intermediate, depending on its makeup, with the resulting energy production or energy storage
• Removal of amino group is a two-step process:

  transamination and oxidative deamination
• Transamination - an enzyme-catalyzed biochemical process in which the amino group of an alpha- amino acid is transferred to an alpha-keto acid
• There are at least 50 transaminase enzymes associated with transamination reactions.
• Oxidative deamination- an amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia and the ammonia eventually goes into the urea cycle.
• • By transamination, the body can manufacture the amino acids that it needs but does not have an essential part of the active site of transaminases 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.
• The ammonium ion produced by oxidative deamination is a toxic substance, so it is quickly converted to carbomyl phosphate and then to urea via the urea cycle in mammals
• In the conversion of ammonia to urea, three different amino acids are involved: arginine, citrulline, and ornithine; the pathway is called urea cycle or Krebs Ornithine Cycle
• The blood picks up the urea from the liver and carries it to the kidneys where it is excreted in the urine
• stage 1: Carbomyl group transfer – The carbamoyl group of carbamoyl phosphate is transferred to ornithine to form citrulline.
• Stage 2: Citrulline-aspartate condensation – Citrulline is transported into the cytosol, citrulline reacts with aspartate to produce argininosuccinate utilizing ATP
• Stage 3: Argininosuccinate cleavage: – Argininosuccinate is cleaved to arginine and fumarate by the enzyme argininosuccinate lyase.
• Stage 4: Hydrolysis of urea from arginine: – Hydrolysis of arginine produces urea and regenerates ornithine - one of the cycle’s starting materials.
• • 7 Degradation products are pyruvate, acetyl CoA, acetoacetyl CoA, alpha-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate
• The amino acids converted to citric acid cycle intermediates can serve as glucose precursors (glucogenic amino acids)
• Glucogenic amino acid: An amino acid that has a carbon-containing degradation product that can be used to produce glucose via gluconeogenesis.
• The amino acids converted to acetyl CoA or acetoacetyl CoA can serve as precursors for fatty acids and/or ketone body synthesis (ketogenic amino acids)
• Ketogenic amino acid: An amino acid that has a carbon-containing degradation product that can be used to produce ketone bodies.
• Red blood cells (RBCs) are highly specialized cells whose primary function is to deliver oxygen to cells and remove carbon dioxide from body tissues.