Protein Protein MetabolismMetabolism

From: Protein Data Bank PDB ID: 1B0EKalus, 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)

Nitrogen balanceNitrogen balance

Protein content of adult body Protein content of adult body

remains remarkably constantremains remarkably constant

Protein constitutes 10-15% of dietProtein constitutes 10-15% of diet

Equivalent amount of amino acids must Equivalent amount of amino acids must

be lost each daybe lost each day

Amino acid poolAmino acid pool No storage facility for No storage facility for

amino acidsamino acids Amino acids incorporated into Amino acids incorporated into

functional proteinsfunctional proteins

Amino acids in blood and Amino acids in blood and extracellular fluid represent extracellular fluid represent an ‘amino acid pool’an ‘amino acid pool’ Amino acids move through Amino acids move through

this poolthis pool Average 60 kg womanAverage 60 kg woman

– 10 kg protein10 kg protein

– 170 g free amino acids in 170 g free amino acids in poolpool

From: Summerlin LR (1981) Chemistry for the Life Sciences. New York: Random House p 563.

Fate of amino acidsFate of amino acids If not required for protein If not required for protein

synthesis amino groups removedsynthesis amino groups removed For most amino acids occurs For most amino acids occurs

primarily in liverprimarily in liver For BCAAs (leucine, isoleucine, For BCAAs (leucine, isoleucine,

valine) occurs primarily in skeletal valine) occurs primarily in skeletal musclemuscle

amino groups transferred to alanine amino groups transferred to alanine and taken to liver for disposal via and taken to liver for disposal via glucose-alanine cycleglucose-alanine cycle

Carbon skeletons used for:Carbon skeletons used for: Gluconeogenesis (in liver)Gluconeogenesis (in liver) Oxidised in Krebs CycleOxidised in Krebs Cycle

Amino groups used forAmino groups used for Synthesis of nonprotein nitrogen Synthesis of nonprotein nitrogen

compoundscompounds disposed of via Urea Cycledisposed of via Urea Cycle

From: Summerlin LR (1981) Chemistry for the Life Sciences. New York: Random House p 563.

Amino acid metabolismAmino acid metabolism

Metabolism of amino acids differs, Metabolism of amino acids differs,

but 3 common reactions:but 3 common reactions:

TransaminationTransamination

DeaminationDeamination

Formation of ureaFormation of urea

Transamination reactionsTransamination reactions Amino group removed from Amino group removed from

one amino acid and one amino acid and transferred to anothertransferred to another Catalysed by aminotransferase Catalysed by aminotransferase

enzymesenzymes Nearly all transaminations Nearly all transaminations

transfer amino group to transfer amino group to --ketoglutarateketoglutarate

Forms new ketoacid and Forms new ketoacid and glutamate (amino acid)glutamate (amino acid)

BCAA transaminations in SM BCAA transaminations in SM usually result in formation of usually result in formation of alanine (via glutamate)alanine (via glutamate)

Released from muscleReleased from muscle Allows amino groups from BCAAs Allows amino groups from BCAAs

to move from SM to liver for to move from SM to liver for disposaldisposal

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

Deamination reactionsDeamination reactions Amino group (and Amino group (and

H) removedH) removed Forms ammonia Forms ammonia

(NH(NH33)) Carbon skeleton left Carbon skeleton left

can becan be Oxidised in KCOxidised in KC used for used for

gluconeogenesisgluconeogenesis converted to fatty acidconverted to fatty acid

18 amino acids 18 amino acids glucogenic/ketogenicglucogenic/ketogenic

Leucine and lysine Leucine and lysine purely ketogenicpurely ketogenic

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

Urea cycleUrea cycle

Ammonia is toxicAmmonia is toxic Readily ionises to Readily ionises to

ammonium ion NHammonium ion NH44++

NHNH44+ + converted to urea converted to urea

in liver (urea cycle)in liver (urea cycle)

– Urea contains 2 x Urea contains 2 x

NHNH22

One from NHOne from NH44++

One from One from

aspartate aspartate

Urea excreted in urineUrea excreted in urine

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