UREA CYCLE & Amino Acid Metabolism Flashcards
step 0
CO2 + NH4+ –> carbamoyl phosphate
Step 1
carbamoyl phosphate + ornithine —> citrulline
citrulline passes into the cytosol
Step 2
citrullyl-AMP intermediate (entry of second amino group) –> arginosuccinate
Step 3
arginosuccinate —> arginine + fumarate (enters citric cycle)
Step 4
arginine + H2O —> Urea + Ornithine
Hydrolysis produces urea, which regenerates ornithine
Nitrate assimilation
Reduction of NO3- to NH4+ occurs in plants, fungi, and bacteria in a two-step process
Nitrogen fixation
formation of NH4+ from N2 gas; exclusively a prokaryotic process.
IN ANIMALS (Nitrogen)
No nitrogen fixation or assimilation; dependent on plants and microorganisms for the synthesis of organic nitrogenous compounds such as amino acids.
Amino Acid Oxidation Occurs when…
- diet rich in proteins and/or ingested amino acids exceeds body’s need for synthesis
- Carnivores derive up to 90% of energy from amino acids
- During starvation, uncontrolled diabetes mellitus or when low carbohydrate diet.
Overview of amino acid catabolism in mammals
- Need to deal with NH4+ because it is toxic in mammals
- The amino groups and the carbon skeleton take separate but interconnected pathways
Part of the human gastrointenstinal tract
(a) protein cause the release of gastrin which causes parietal cells to secrete HCl and chief cells to secrete pepsinogen
(b) Low pH in intestine secretin released into the blood, which causes the pancreas to release HCO3- into the intestine.
- Exocrine cells release proteases like trypsin into pancreatic duct which leads to the small intestine.
(c) individual Amino Acids absorbed by transporters
Acute Pancreatitis
Disease where pancreatic duct is blocked and the proteolytic zymogens are converted to active enzymes that degrade the lining of the pancreas.
Where are amino acids metabolized?
The liver
- Amino groups are shuttled to liver in form of GLUTAMINE from most tissues but also as ALANINE from muscle
- Amino groups are converted to urea in mammals for excretion in urine
Enzyme-catalyzed Transaminiations
- Alpha-ketoglutarate is the amino group acceptor.
- All aminotransferases have pyridoxal phosphate (PLP) as a cofactor.
- Reaction is readily reversible; happens in liver.
- Collect amino groups in liver from many amino acids as gultamate – a universal amino donor.
Pyridoxal phosphate —> the prosthetic group of aminotransderases
- Coenzyme form of pyrido-xine vitamin B6
(a) PLP and its aminated form, pyradoxamine phosphate, tightly bound coenzymes of aminotransferases.
- bound to the enzyme through Schiff-base linkage to a Lys residue at the active site as well as non-covalent interactions
How does Glutamate Dehydrogenase catalyze ammonium production (NH4+)?
Through oxidative deamination in mitochondria; glutamate dehydrogenase has the unusual capacity to use either NAD+ or NADP+ as cofactor.
How is ammonia transported from other tissues to the liver?
- Form of glutamine, then converted back to glutamate
- Excess ammonia in tissues added to glutamate to form glutamine, process catalyzed by GLUTAMINE SYNTHETASE.
- After transport in bloodstream, glutamine enters the liver and NH4+ is liberated in mitochondria by the enzyme GLUTAMINASE.
Glucose-Alanine Cycle
- Alanine serves as carrier of ammonia & carbon skeleton of pyruvate from SKELETAL MUSCLES TO LIVER.
Ammonia is excreted and pyruvate is used to produce GLUCOSE, RETURNED TO THE MUSCLE.
Major amino group transfers: Glutamate
Glutamate dehydrogenase in liver mitochondria removes alpha-amino group from glutamate, releases ammonia and regenerates alpha-ketoglutarate
Major amino group transfers: Glutamine
Glutamine will be degraded by glutaminase in the mitochondria of liver cell into glutamate and ammonia.
Major amino group transfers: Alanine
Degraded in the liver through transamination reaction with alpha-ketoglutarate and this will regenerate pyruvate.
–>Pyruvate can be used to generate glucose which will enter the blood to supply muscle for glycolysis.
Urea cycle and reactions that feed amino groups into the cycle
- Takes place in mitochondria and cytosol of liver
- One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix
- The other amino group enters as ASPARTATE, formed in the matrix by transamination of oxaloacetate by glutamate.
Energetic Cost of Urea Synthesis
- Four high energy bonds since ATP is converted to AMP
- 4 ATP bonds but get 2.5 ATPs back so about 1.5 ATP/Urea
