Amino acid degradation in animals
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Transcript Amino acid degradation in animals
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