Metabolism of Ammonia and Amino Acids

Metabolism of Ammonia (NH3)

• Sources of Ammonia in Peripheral Blood:
  • Deamination of amino acids (main source).
  • Putrefaction of urea in the colon by bacteria.
  • Hydrolysis of glutamine by glutaminase in the kidney.
• Transport of Ammonia:
  • Alanine-glucose cycle: Transports NH3 from muscle to liver.
    • Significance: Transfers NH3 to the liver via alanine and supplies glucose for the muscle.
  • Glutamine: Transports NH3 from the brain and muscle to the liver and kidney.
• Formation of Urea:
  • Main metabolic pathway for NH3 in the body (80-90%) occurs in the liver.
  • Urea biosynthesis is carried out by the urea cycle (ornithine cycle).
  • The urea cycle occurs in mitochondria and cytoplasm of liver cells.
  • Steps of Urea Cycle:
    1. Synthesis of carbamoyl phosphate (Key enzyme: Carbamoyl phosphate synthetase (CPS-I), Activator: N-acetyl, AGA).
    2. Formation of citrulline.
    3. Formation of argininosuccinate.
    4. Hydrolysis of argininosuccinate to release arginine and fumarate.
    5. Hydrolysis of arginine to release urea.
  • Two "N" in urea: one is from NH3, and the other is from aspartate.
  • The urea cycle consumes ATP.
• Hyperammonemia:
  • Occurs in chronic or acute liver failure.
  • High levels of blood NH3.
  • Leads to hepatic coma.

Individual Amino Acid Catabolism

• Decarboxylation of Amino Acids:
  • Amino acids are decarboxylated to form corresponding amines by amino acid decarboxylase.
  • $R-CH(NH<em>2)COOH \rightarrow R-CH</em>2NH<em>2 + CO</em>2$
  • Examples:
    • GABA: Formed from glutamate; inhibitory neurotransmitter.
    • Histamine: Formed from histidine; vasodilator, stimulates pepsin and hydrochloric acid secretion.
    • 5-HT (Serotonin): Formed from tryptophan; inhibitory neurotransmitter.
    • Polyamines (Spermidine and Spermine): Important in cell proliferation and tissue growth.
• Metabolism of One Carbon Units:
  • One carbon units are organic groups containing one carbon atom produced in the catabolism of some amino acids.
  • Examples: Methyl, Methenyl, Methylene, Formyl, Formimino.
  • Tetrahydrofolic acid (FH4) is the transport carrier of one-carbon units.
  • One carbon units are derived from amino acids (Tryptophan, Histidine, Glycine, Serine).
  • Function: Serve as materials for purine and pyrimidine synthesis.
  • Megaloblastic Anemia: Can result from folic acid deficiency, impairing DNA replication.
  • Sulfonamides: Inhibit FH4 synthesis in bacteria.

Metabolism of Sulfur-Containing Amino Acids

• Examples: Cysteine, Methionine, Cystine.
• Metabolism of Methionine:
  • Methionine Cycle:
    • Methionine is converted to S-Adenosyl-methionine (SAM).
    • The methyl group in SAM is the "active methyl group" that can be transferred to many substrates for methylation.
    • Methylation reactions are catalyzed by methyl transferase with SAM as the methyl group donor.
  • Creatine and Creatine Phosphate:
    • Important for energy storage and utilization in skeletal muscle.
    • Synthesized in the liver using glycine, arginine, and methionine.
  • Creatine Kinase (CK):
    • Composed of two types of subunits: B (brain type) and M (muscle type).
    • Three isoenzymes: CK1 (BB), CK2 (MB), and CK3 (MM).
    • Elevated levels of MB type in blood indicate myocardial infarction.
• Metabolism of Cysteine and Cystine:
  • Conversion of Cysteine and Cystine: Disulfide bond formation of cystine is important to maintain protein conformation and function.
  • Formation of 3’-Phosphoadenosine 5’-Phosphosulfate (PAPS): Cysteine is the main source of sulfate in the body, and PAPS provides the active sulfate group.
  • Synthesis of Taurine: Taurine is a partial composition of conjugated bile acids in bile.
  • Synthesis of Glutathione: Glutathione acts as a reductant, protecting sulfhydryl enzymes from oxidative damage.