Chapter 18
Amino Acid Oxidation and The
Production of Urea
Amino Acid Oxidation
 Dependency of amino acid as energy source
 Carnivores> herbivores> microorganism >> plant
 Amino acid degradation in animals


Amino acids for oxidation
 Extra amino acid during protein turnover
 Protein-rich diet (no storage)
 During starvation or in uncontrolled diabetes
Removal of amino group (NH4+)
 a-keto acid (C skeleton of amino acids)
 Oxidation to CO2 & H2O
 Sources of C3 or C4 units for gluconeogenesis or fuels
Pathways of amino acid catabolism
18.1 Metabolic Fates of Amino Groups
Amino Group Catabolism
Amino Group Catabolism
 Amino acid metabolism
 amino group (= nitrogen metabolism)
 Liver is a major site

 Recycle for biosynthetic pathways
 Excretion; ammnonia, urea, uric acid
Glutamate & glutamine
 General collection point for amino group
 NH3 from amino acids + a-ketoglutarate
 glutamate
into mitochondria, 
release of NH4+
 Source of ammonia
 Dietary protein (major source)
 Muscle & other tissues
NH4+ + glutamate  glutamine
 mitochondria in hepatocytes
NH4+ + pyruvate  alanine  hepatocytes
Digestion of Dietary Protein
 In stomach
 Entry of diet  secretion of gastrin from gastric mucosa
 secretion of HCl (parietal cells), pepsinogen (chief cells)

Acidic gastric juice (pH 1.0 to 2.5)

Pepsinogen : zymogen
 Antiseptic & denaturing agent (protein unfolding)
 Conversion to active pepsin by autocatalytic cleavage (at low pH)
 Digestion of peptide bonds at Phe, Trp, Tyr  mixture of small peptides
 In small intestine
 Low pH  secretion of secretin
 stimulation of bicarbonate secretion from pancreas  neutralization
 Arrival in the upper part of intestine (duodenum)
 release of cholecystokinin into blood
 stimulation of pancreatic zymogens
 Trypsinogen : activated by enteropeptidase
 Chymotrypsinogen, procarboxypeptidase A and B : activated by trypsin
c.f.) Protection of pancreas from proteolytic digestion


 Production of zymogens
 Pancreatic trypsin inhibitor
Protein digestion by trypsin, chymotrypsin, carboxypeptidase, aminopeptidase
Uptake of amino acids by the epithelial cells
Digestion of Dietary Protein
Blood capillaries
Liver
Transamination
 1st step of amino acid catabolism
 Transfer of a-amino group to a-ketoglutarate
 Generation of L-glutamate & a-ketoacid
 Aminotransferase (transaminase)
 Amino acid specificity (named after amino
acids)
 Reversible reaction
; ∆G’° ≈ 0 kJ/mol
 Pyridoxal phosphate (PLP)
 Bimolecular Ping-Pong reactions
Pyridoxal phosphate (PLP)
 Coenzyme form of pyridoxine (vitamin B6)
 Intermediate carrier of amino group
 Electron sink for carbanion (resonance stabilization)
 Transamination
 Racemization (L- & D-form interconversion)
 Decarboxylation
PLP-mediated transamination
at a-carbon
PLP-mediated transamination: Ping-Pong mechanism
amino acid
pyridoxal phosphate
a-ketoglutarate
pyridoxamine phosphate
a-keto acid
pyridoxal phosphate
glutamate
PLP-mediated amino acid
transformations at a-carbon
Oxidative Deamination of Glutamate
 Oxidative deamination


Mitochondrial matrix of hepatocytes
Glutamate dehydrogenase
 Generation of a-ketoglutarate & ammonia
 NAD+ or NADP+ as electron acceptor
 Intersection of C and N metabolism
 Allosteric regulation
 By ADP (inhibition)
 By GTP (activation)
 Transdeamination


Transamination + oxidative deamination of Glu
A few amino acids undergoes direct oxidative deamination
Glutamine as Ammonia Carrier in the
Bloodstream
 Ammonia generated in extrahepatic
tissues
 Glutamine synthetase
 Incorporation of ammonia into
glutamate  glutamine
 Transport of gln to the liver via blood
 Higher gln concentration than other
amino acids in blood
 Glutaminase in the liver, intestine,
and kidney
 Glutamine  Glutamate + NH4+
Alanine Transports Ammonia from
Skeletal Muscles to the Liver
 Glucose-alanine cycle
 In muscle
 Glycolysis & degradation of amino acids
 Alanine aminotransferase
 Transfer amino group of glutamate to
pyruvate  alanine + a-ketoglutarate
 Transport of alanine to the liver
 In the liver
 Alanine aminotransferase
 Transfer amino group of alanine to aketoglutarate  glutamate + pyruvate
 Gluconeogenesis
 Pyruvate , lactate  glucose
 Transport of glucose to muscle
Ammonia is toxic to animals.
Comatose state of brain (high brain’s water content)
1. NH3: alkalization of cellular fluid
2. a-ketoglutarate, NADH, ATP:
citric acid cycle & ATP production
3. glutamate and GABA (g-aminobutyrate):
neurotransmitter depletion