Deamination of AA and the Urea Cycle

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Deamination of AA and the Urea Cycle
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Overview dietary origin of amino acids
INGESTED PROTEIN
PEPSIN
STOMACH
PEPTIDES
TRYPSIN CHYMOTRYPSIN CARBOXYPEPTIDASES AMINOPEPTID
ASE
SMALLER PEPTIDES
SMALL INTESTINE
AA SHORT PEPTIDES
BLOODSTREAM
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Nitrogen Balance
N balance - Amount of N consumed equals N
released. True of healthy, well-fed adult ( 75
of AAs from body protein turnover is re-used for
synthesis of new protein remaining 25 is
converted to other N-containing compounds or
oxidized) Negative N balance- More N leaves than
enters Occurs in either protein malnutrition or
disease( protein-derived AAs are used for
energy) Positive N balance- Incorporating more N
than losing due to growth/tissue replacement
Occurs in infants and children.
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Oxidation of AAs as fuel occurs to significant
extent in three conditions
1) Normal turnover of proteins, if amino acid
levels are high 2) High protein diet (amino acids
not stored) 3) Starvation or disease state
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Breakdown of amino acids
AA lose their
amino groups
NH4 1. recycled 2. excreted as NH4
urea uric acid
a-keto acids 1. oxidized to CO2 H2O 2.
provide 3- and 4-carbon units that can be
converted to Glc
Glutamate plays a key role.
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AA catabolism is by removal of N and oxidation
of C skeleton
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Collects AAs from protein digestion and NH3 from
amino acid oxidation in other tissues.
Intestinal bacteria also generate NH3 which is
absorbed and carried to the liver.
Liver, the primary N-metabolizing organ
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1 Transamination
Transamination reactions a-amino groups of AA
are transferred to a-ketoglutarate forming
glutamate Aminotransferases Different
aminotransferases, with specificity for different
AA. using a carrier of amino groups pyridoxal
phosphate (PLP)
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Gln and Ala are the most common NH3 carriers
Gln formed from Glu, is a general carrier, from
muscle and from other tissuesfast fixing of
toxic NH3 Ala is used by muscle to provide
precursor (Pyr) to liver for gluconeogenesis
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2 Oxidative deamination of glutamate
In matrix of liver mitochondria, by glutamate
dehydrogenase (use either NAD or NADPH )
Citric acid cycle Glucose synthesis
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Excretory forms of nitrogen reflect organismss
habitat
Release NH4 to aqueous environment, in which it
is diluted
Urea diluted and excreted in urine
Cant afford to lose the relatively large
volume of water needed to dilute urea insoluble
uric acid excreted in semi-solid form Note
uric acid end-product of purine catabolism in
primates as well as birds, reptiles
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Urea Cycle

• Essential for N removal in animals
• Takes place in liver
• Reactions distributed between mitochondria and
  cytosol

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The Urea Cycle - Liver
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Production of urea from ammonia
Occurs in 5 steps
Formation of carbamoyl phosphate by carbamoyl
phosphate synthetase
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Overall reaction 2NH3 HCO3- 3ATP4- H2O
---------------gt Urea 2 ADP3- 4 Pi2- AMP2-
5H
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The urea and citric acid cycles are linked
FUMARATE GENERATED IN THE UREA CYCLE CAN
REPLENISH THE CITRIC ACID CYCLE
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Krebs Bicycle
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Fates of the 20 AA after deamination
aa that are degraded to acetyl CoA are
ketogenic aa degraded to pyruvate, a-ketoglutar
ate, succinyl CoA, fumarate, or oxaloacetate
glucogenic
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Key Points

• Protein turnover and intake of excess AAs
  results in oxidation of AAs for energy - NH3
  removal is a step common to all AA oxidation
  pathways
• N excreted by animals mostly as urea. Glu and
  Gln are the most important AAs in NH3removal
• Liver is the main N-metabolizing organ
• Urea cycle reactions occur in mitochondria and
  cytosol