Amino Acid Catabolism Flashcards
circumstances of protein catabolism
normal protein synthesis and degradation
intake exceeds body’s need (no storage)
starvation
uncontrolled diabetes or cancer
Protein digestion pathway
1) protein in stomach stimulates gastrin secretion from mucosa, stimulating secretion of HCl and pepsinogen
2) low pH activates pepsinogen –> pepsin cleaving long polypeptides at specific AA into smaller ones
3) chyme moves to SI, triggering secretin hormone in blood, trigger pancreas to secrete HCO3- to neutralize pH
4) protein in SI triggers hormone cholecystokinin which stimulates release of pancreatic enzymes: trypsin and chymotrypsin into smaller polypeptides
5) carboxypeptidase and aminopeptidase cleave polypeptides into amino acids ready for absorption
Step 1 amino group catabolism
Amino group removal or transamination reaction
Transfer of amino group from amino acid to alpha-ketoglutarate forming L-Glutamate and keto acid byproduct
Enzyme: aminotransferase (AA specific)
Cofactor: PLP (pyridoxal phosphate B6)
Location: liver and other tissues mitochondria
Purpose: collect the amino groups from many different amino acids in the form of L-glutamate which then functions as an amino group donor for biosynthetic pathways
Step 2 amino group catabolism
Activator/inhibitor
Amino group release into urea cycle: transfer from glutamate to reform alpha-ketoglutarate
Enzyme: Glutamate dehydrogenase
Cofactor: 1) NADP+ 2) H2O
Location: liver mitochondria
Activator: ADP allosteric activator of glutamate dehydrogenase
Inhibitor: GTP inhibits glutamate dehydrogenase
Transport of ammonia from other tissues besides liver
1) glutamate converted to glutamyl-phosphate and then glutamine by addition of ATP then NH4+
Enzyme: glutamine synthetase x2
Cofactors: ATP then NH4+
2) glutamine can be transported to the liver
3) glutamine converted back to glutamate
Enzyme: glutaminase
Cofactor: H2O
Location: liver mitochondria
Transport of ammonia from muscle tissue
Glucose-alanine cycle
1) NH4+ transferred to form glutamate (same start as other pathway)
2) Amino group transferred to pyruvate to form alanine and reform alpha-ketoglutarate byproduct
Enzyme: alanine aminotransferase
3) Alanine travels in the blood to the liver where it is converted back to pyruvate and glutamate
Enzyme: alanine amino transferase
Cofactor: alpha-ketoglutarate
4) Glutamate releases NH4+ into urea cycle
Enzyme: glutamate dehydrogenase
Cofactor: 1) NADP+ 2) H2O
5) Pyruvate –> glucose via gluconeogenesis
Mitochondrial portion of urea cycle
1) NH4+ from glutamate + HCO3- + 2ATP –> carbamoyl phosphate
Enzyme: carbamoyl phosphate synthetase I
2) Carbamoyl phosphate + ornithine –> citrulline
Enzyme: ornithine transcarbamoylase
Citrulline can then pass from mitochondria to cytosol
Cytosolic portion of urea cycle (main pathway)
1) Citrulline converted to Citrulline-AMP intermediate
Enzyme argininosuccinate synthetase
Cofactor: ATP
2) Citrulline-AMP intermediate + aspartate –> argininosuccinate + AMP
Enzyme argininosuccinate synthetase
3) Argininosuccinate –> fumarate + arginine
Enzyme: argininosuccinase
4) Arginine –> ornithine + urea released
Enzyme: arginase
Cofactor: H2O
Ornithine can then return to mitochondrial matrix to form citrulline again
Urea cycle production of aspartate
1) oxaloacetate + glutamate –> aspartate + a-ketoglutarate
Enzyme: aspartate aminotransferase
Location: mitochondrial matrix (liver)
Moves to cytosol
2) aspartate + citrulline-AMP intermediate –> argininosuccinate + AMP
Enzyme: argininosuccinate synthetase
Location: cytosol of liver cell
**Rest of urea cycle continues as same:
**3) Argininosuccinate –> fumarate + arginine
Enzyme: argininosuccinase
4) Arginine –> ornithine + urea released
Enzyme: arginase
Cofactor: H2O
Ornithine can then return to mitochondrial matrix to form citrulline again
Stimulation of urea cycle pathway
High [acetyl-CoA] and [glutamate]
1) acetyl-coA + glutamate –> N-acetylglutamate
Enzyme: N-acetylglutamate synthase
2) N-acetylglutamate activates carbamoyl phosphate synthetase I for mitochondrial portion of urea cycle
High [arginine]
Acts as activator of N-acetylglutamate synthase
Aspartate-argininosuccinate shunt
Malate-aspartate shuttle: fumarase and malate dehydrogenase have isozymes in cytosol
1) From argininosuccinate –> arginine + fumarate in urea cycle fumarate can be converted to malate by fumarase and re-enter mitochondria for TCA
2) Aspartate formation from urea cycle can enter cytosol and reform oxaloacetate, and then form malate to re-enter mitochondrial matrix TCA
- this is also the malate-aspartate shuttle to move NADH from cytosol to mitochondrial matrix
Percent energy production from AA catabolism
Products from AA catabolism that can enter TCA
10-15%
alpha-ketoglutarate
succinyl-coA
fumarate
oxaloacetate
pyruvate via oxaloacetate and acetyl coA
acetyl coA
Not acetoacetyl-CoA (ketogenic)
amino acids that yield acetyl coA and acetoacetyl-coA are
ketogenic
acetoacetyl-coA formed: leucine, lysine, phenylalanine, tryptophan, tyrosine
acetyl coA formed: isoleucine, leucine, threonine, tryptophan (can be gluco or ketogenic)
Strictly ketogenic amino acids
lysine and leucine
branched chain amino acid catabolism
Leucine, Isoleucine and Valine
Only used for fuel in the brain, muscle and adipose tissue
Branched chain aminotransferase expressed only outside the liver (otherwise most AA catabolism occurs in liver)
