Protein Metabolism

1
Protein Metabolism
From Protein Data Bank PDB ID 1B0E Kalus, W.,
Zweckstetter, M., Renner, C., Sanchez, Y.,
Georgescu, J., Grol, M., Demuth, D., Schumacher,
R., Dony, C., Lang, K., Holak, T. A. structure
of the IGF-binding domain of the insulin-like
growth factor-binding protein-5 (IGFBP-5)
implications for IGF and IGF-I receptor
interactions. EMBO J 17 pp. 6558 (1998)
2
Nitrogen balance

• Protein content of adult body remains remarkably
  constant
• Protein constitutes 10-15 of diet
• Equivalent amount of amino acids must be lost
  each day

3
Amino acid pool

• No storage facility for amino acids
• Amino acids incorporated into functional proteins
• Amino acids in blood and extracellular fluid
  represent an amino acid pool
• Amino acids move through this pool
• Average 60 kg woman
• 10 kg protein
• 170 g free amino acids in pool

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 563.
4
Fate of amino acids

• If not required for protein synthesis amino
  groups removed
• For most amino acids occurs primarily in liver
• For BCAAs (leucine, isoleucine, valine) occurs
  primarily in skeletal muscle
• amino groups transferred to alanine and taken to
  liver for disposal via glucose-alanine cycle
• Carbon skeletons used for
• Gluconeogenesis (in liver)
• Oxidised in Krebs Cycle
• Amino groups used for
• Synthesis of nonprotein nitrogen compounds
• disposed of via Urea Cycle

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 563.
5
Amino acid metabolism

• Metabolism of amino acids differs, but 3 common
  reactions
• Transamination
• Deamination
• Formation of urea

6
Transamination reactions

• Amino group removed from one amino acid and
  transferred to another
• Catalysed by aminotransferase enzymes
• Nearly all transaminations transfer amino group
  to ?-ketoglutarate
• Forms new ketoacid and glutamate (amino acid)
• BCAA transaminations in SM usually result in
  formation of alanine (via glutamate)
• Released from muscle
• Allows amino groups from BCAAs to move from SM to
  liver for disposal

From Houston, ME. (2001) Biochemistry Primer
for Exercise Science. Champaign Human Kinetics.
p151
7
Deamination reactions

• Amino group (and H) removed
• Forms ammonia (NH3)
• Carbon skeleton left can be
• Oxidised in KC
• used for gluconeogenesis
• converted to fatty acid
• 18 amino acids glucogenic/ketogenic
• Leucine and lysine purely ketogenic

From Houston, ME. (2001) Biochemistry Primer
for Exercise Science. Champaign Human Kinetics.
p148
8
Urea cycle

• Ammonia is toxic
• Readily ionises to ammonium ion NH4
• NH4 converted to urea in liver (urea cycle)
• Urea contains 2 x NH2
• One from NH4
• One from aspartate
• Urea excreted in urine

From Stryer, LS (1988) Biochemistry (3rd Ed).
New York WH Freeman Co. p500