Amino Acid Metabolism - Lecture 1 Notes

Amino Acid Metabolism Lecture 1

Introduction

  • This lecture is the first of two on amino acid metabolism.
  • The first lecture will cover the first two and a half learning objectives, and the second lecture will cover the remaining two and a half.

Review of Proteins and Amino Acids

  • Common Structure of Amino Acids:
    • A central alpha carbon.
    • A hydrogen atom.
    • A side chain (R-group).
    • An amine group (NH2).
    • A carboxylic acid group (COOH).
  • Glycine:
    • The only non-chiral amino acid because its side chain is another hydrogen atom.
  • Hydrophobic Amino Acids:
    • Generally found on the inside of proteins dissolved in water or on the outside of proteins in cell membranes.
  • Water-Soluble and Polar Amino Acids:
    • Charged amino acids are water-soluble and polar.
  • Special Cases:
    • Proline:
      • Used to create turns in amino acid sequences.
    • Cysteine:
      • Contains sulfur, which can form disulfide bonds with other cysteines.
      • Methionine is another sulfur-containing amino acid with a methyl group on the end.
      • Disulfide bonds are important in hair structure.
      • Chemical hair straightening involves breaking these disulfide bonds.
      • Glutathione is a tripeptide linked through a disulfide bond.
  • Peptide Bonds:
    • Amino acids link together to form peptides.
    • Peptides are short proteins.
    • Peptide bonds are formed between the carboxylic acid group of one amino acid and the amine group of the next amino acid.
    • When proteins are broken down, the cuts occur at the peptide bonds.
    • Breaking a peptide bond does not change the identity of the amino acid.

Protein Structure

  • Four Levels of Protein Structure:
    • Primary Structure:
      • The amino acid sequence, determined by DNA through RNA.
    • Secondary Structures:
      • Alpha helix.
      • Beta-pleated sheets.
      • Random coil.
      • Turns.
    • Tertiary Structure:
      • The specific three-dimensional folding of a protein.
      • Essential for protein function.
      • Example: The story of denosumab and the ship from Norway, Denmark, highlights the importance of maintaining the correct tertiary structure.
    • Quaternary Structure:
      • The arrangement of multiple protein subunits.
      • Example: Hemoglobin, which consists of four subunits.
  • Proteins must have specific shapes to function correctly.

Uses of Amino Acids in the Body

  • Amino acids are not solely for making proteins.
  • They are used to produce ATP.
  • They are used to produce chemicals that go into the Krebs cycle.
  • Amino acids can be used to produce glucose.
  • Nitrogen can be extracted from amino acids.
    • This process produces ammonia, which is converted to urea and excreted in urine.
    • Nitrogen can also be used to make other amino acids.
  • Amino acids are used to make other compounds.
    • Tyrosine is used to make adrenaline (epinephrine).
  • Glutamate (glutamic acid with a negative charge) is a key signaling molecule in the brain.
    • Ketamine raises glutamate levels in the brain, which can have antidepressant effects.

Protein Digestion and Absorption

  • The body breaks down ingested proteins into their fundamental parts and rebuilds what it needs.
  • Animal products (e.g., meat, milk) contain all the components needed to make a human.
  • The five food groups are a myth.
  • The composition of the food groups has changed over time.
  • People can survive on diets consisting solely of meat or solely of fruits and vegetables.
  • In the stomach:
    • Hydrochloric acid denatures proteins.
    • Pepsin, a protease, breaks down proteins by cleaving peptide bonds.
    • Testing saliva for pepsin can indicate reflux.
  • The stomach breaks down solids into a liquid.
  • Small, uncharged substances like aspirin and paracetamol can be absorbed in the stomach.
  • In the small intestine:
    • Major absorption occurs.
    • Chymotrypsin and trypsin (proteases produced by the pancreas) further break down proteins into amino acids, dipeptides, or tripeptides.
    • Amino acids and small peptides are absorbed into the liver for first-pass metabolism and then into the bloodstream.
    • Proteases cleave only peptide bonds.

Essential Amino Acids

  • Lysine Contingency (Jurassic Park):
    • In the movie, dinosaurs were engineered to require lysine to prevent them from escaping and spreading.
    • They would slip into a coma and die without a constant supply of lysine.
    • In the sequel, the dinosaurs survived by eating lysine-enriched plant matter.
  • Lysine is an essential amino acid.
  • Essential amino acids cannot be synthesized by the body and must be obtained from the diet.
  • The animals can't produce lysine anyway.
  • There are ten essential amino acids (nine if you exclude arginine, which is pseudo-essential).
  • Arginine is considered pseudo-essential because the body cannot produce enough of it to meet its needs.
  • Essential amino acids are primarily obtained from eggs and meat.
  • A food source containing all nine essential amino acids is called a complete protein.
  • Vegans and vegetarians can obtain essential amino acids by consuming legumes, peas, lentils, beans, nuts, seeds, or grains.

Protein Recycling and Ubiquitin

  • Proteins get old, denatured, and damaged, so the body needs to recycle them.
  • Lysosomal proteases degrade old proteins.
  • Ubiquitin:
    • Discovered and recognized in 2002/2004 (Nobel Prize).
    • The body uses ubiquitin to tag proteins for breakdown.
    • Ubiquitin is a signaling molecule that marks proteins that need to be broken down.
    • Ubiquitin is added to the end of proteins via an isopeptide bond.
    • Polyubiquitin chains are added to ensure the protein is tagged for breakdown.
  • Proteases recognize and bind to ubiquitin, then break down the tagged proteins.
  • This process is non-lysosomal and ATP-dependent.
  • The proteasome targets and degrades proteins tagged by ubiquitin.

Amino Acid Storage and Conversion

  • Unlike glucose, the body has no way of storing amino acids.
  • Excess amino acids are converted into other substances.
  • Excess protein can lead to weight gain because the body converts amino acids into glucose and fatty acids for storage.
  • Amino acids can be converted into nucleotides.
  • Amino acids can feed into pyruvate or acetyl coenzyme A.
  • Amino acids can be converted to urea or other compounds to deal with toxic ammonia.
  • Amino acids can feed into the citric acid cycle or the electron transport chain to produce ATP.
  • Even eating protein can help you put on weight if you eat too much.

Glucogenic and Ketogenic Amino Acids

  • Amino acids can be used to make sugars.
    • They feed into pyruvate or acetyl coenzyme A and then can be used to make glucose.
  • Glucogenic Amino Acids:
    • Amino acids that can be converted into glucose.
    • There are 14 purely glucogenic amino acids.
  • Ketogenic Amino Acids:
    • Amino acids that can be converted into ketones.
    • Some amino acids can be either glucogenic or ketogenic.
  • Example: L-Serine
    • Loses water (H and OH) in a reaction catalyzed by PLP (pyridoxal phosphate).
    • Forms a double bond, creating pyruvate.
    • Pyruvate feeds into gluconeogenesis to make glucose.
  • Pyridoxal Phosphate (PLP):
    • A cofactor involved in various reactions, including decarboxylation, elimination reactions (beta-elimination), racemization, and retro aldol reactions.
  • Ketogenic Amino Acids:
    • Can make ketone groups (carbon double-bonded to oxygen with carbons on either side).

Amino Acid Breakdown Processes

  • Deamination:
    • The removal of an amine group.
    • The amine group goes into the urea cycle.
    • The carbon skeleton can be used to make acetyl coenzyme A in the Krebs cycle, glucose, carbon dioxide and water, and ketone bodies.
    • Knowing key enzymes like PLP is important for the exam.
  • Oxidative Deamination:
    • Primarily relevant for glutamic acid.
    • Involves removing an amine group and adding an oxygen.