HBG 14 ( Protein)

• Metabolic pathways in the body include: Pentose phosphate, nucleic acids (DNA, RNA), amino acids, proteins, glucose, pyruvate, acetyl CoA, glycogen/CHO, TCA cycle, CO2, FADH2, NADH, ETC, ATP, CO2, NADPH, fatty acids, aspartate, urea cycle, urea, ATP
• Overview of protein and nitrogen metabolism
• Protein turnover and metabolism of amino nitrogen
• Amino acid catabolism includes ammonia and urea metabolism, urea cycle
• Protein turnover involves nitrogen balance & protein breakdown mechanism
• Two pathways for protein breakdown
• Metabolism of nitrogen from amino acid includes transamination
• Clinical significance of aminotransferase enzymes
• Oxidative deamination & non-oxidative deamination
• Generation of new amino acids (Biosynthesis of amino acids)
• Nitrogen balance is the balance between nitrogen intake (Diet) & nitrogen excretion
• Positive nitrogen balance occurs when nitrogen intake > excretion, e.g. growing age, pregnancy, convalescence
• Negative nitrogen balance occurs when nitrogen loss > nitrogen intake, e.g. during illnesses, injury, fasting, surgery, lack of essential amino acids
• Protein synthesis is controlled by hormones
• Anabolic hormones promote protein synthesis: GH, insulin, testosterone, T3 & T4 (normal level)
• Catabolic hormones promote protein breakdown: 11-oxysteroids, T3 & T4 (hyper level)
• Protein breakdown mechanism involves ATP and Ubiquitin dependent pathway for short-lived intracellular proteins
• ATP independent lysosomal pathway for long-lived extracellular proteins
• Short-lived proteins include regulatory enzymes (e.g. hormones & some enzymes) that last minutes to hours
• Long-lived proteins include most intracellular proteins that last days to weeks
• Structural proteins are very stable and last months to years, e.g. hairs & nails
• Determined by N-terminal amino acid (known as N-end role)
• Lysosomal enzymes are used for extracellular proteins, e.g. plasma protein
• Flow of nitrogen from amino acid to urea involves transamination, oxidative deamination & non-oxidative deamination
• Biosynthesis of non-essential amino acids includes transamination, oxidative deamination, ammonia transport, urea cycle
• Essential amino acids come from the diet, while non-essential amino acids can be synthesized
• Out of 11 non-essential amino acids, 8 are synthesized from amphibolic intermediates
• 3 are synthesized from essential amino acids
• Glucose, phosphoglycerate, pyruvate, acetyl-CoA, citrate, isocitrate, a-KG, oxaloacetate, Kreb’s cycle, Met (S), Ala, Ser, Cys, Gly, Ala, Asp, Asn, Gln, Glu, Gln, Glu semialdehyde, Pro, Arg, Phe, Tyr
• Growing children, post-operative condition, pregnancy, convalescence, injury
• Amino acid pool includes free amino acids in the cells & ECF, diet, synthesis of non-essential amino acids, body protein degradation, body protein synthesis, synthesis of N2 containing compounds, protein turnover, N2 balance, Ubiquitin pathway, Lysosomal pathway
• Protein turnover involves simultaneous synthesis of body proteins, degradation of body proteins
• Regulated by hormones: anabolic hormones promote protein synthesis, catabolic hormones promote protein breakdown
• Regulated by Ubiquitin dependent and Ubiquitin independent pathways, PEST sequences
• Removal of N2 from amino acid involves transamination, oxidative deamination, transport of NH3 to liver, urea cycle
• Ammonia metabolism:

  • Sources of ammonia
  • Ammonia blood level and transportation
  • Hyperammonemia and ammonia intoxication
  • Mechanism of ammonia intoxication
• Urea cycle
• Metabolism of carbon skeleton:

  • Pyruvate, Acetyl CoA, Acetoacetyl CoA
  • α-ketoglutarate
  • Succinyl CoA
  • Fumarate
  • Oxaloacetate
• Genetic defects in catabolism of some amino acids
• Catabolism of amino acids:

  • Transamination
  • Oxidative deamination
  • Ammonia transport
  • Urea cycle