ROS and Urea Cycle Flashcards
Triplet Oxygen
The oxygen that we breathe. No double bond, one unpaired electron on each oxygen spinning in the same direction. Unreactive. If it gains an electron, it can become a superoxide radical, can gain another to be peroxide. Will become H2O2, will split after it gains an electron to form H2O and OH radical. OH radical can gain an electron and eventually become water.
Oxidative Stress
Imbalance between antioxidants/oxygen radicals
Singlet Oxygen
O2 with a single bond and unpaired electrons on each oxygen spinning in the opposite direction. Dangerous, can insert across double bonds.
Hydrogen Abstraction
Oxygen radical can steal a hydrogen, generating another radical.
OH.+LH –> H2O + L.
Disproportionation
Where two radicals come together, but instead of terminating, one is oxidized and one is reduced. O2.+O2. +2H–>O2+H2O2
Haber Weiss and Fenton Reactions
Fe-based generation of OH radicals, using H2O2.
Why are ROS toxic?
1) They can affect proteins (Oxidize SH, fragment aromatic aa’s).
2) They can affect lipids (destroy cell membranes).
3) They can affect DNA (cleave backbone, excise bases, oxidize bases).
Autooxidation of Quinones
If ubi gains electron, it becomes semiquinone radical, which can create O2 radical. If it doesn’t semiquinone can gain another electron and become ubiquinol.
Superoxide Dismutase
Enzyme that protects against ROS.
O2.+O2. +2H -> O2 + H2O
SOD 1 uses Copper/Iron, SOD2 uses Manganese.
Catalase Reaction
2H2O2 –> 2H2O + O2
Peroxidase Reaction
H2O2 + SH2 –> S + 2H2O
How are ROS beneficial?
Can mount respiratory burst in macrophages/phagocytes to kill foreign bacteria. Needed for ribonucleotide reductase, also needed for methylmalonyl CoA mutase.
Reperfusion Injury
When a tissue is hypoxic, Adenine can be turned into Hypoxanthine which can be turned into Xanthine (or generated from guanine) using Xanthine Dehydrogenase. Xanthine become uric acid via another xanthine dehydrogenase reaction. When oxygen is reintroduced into this tissue, Xanthine reductase can generate ROS.
Desferal and Allopurinol
Desferal is an iron chelator that stops the fenton reaction. Allopurinol is a Xanthine oxidase inhibitor.
Essential Amino Acids
Phenylalanine Valine Tryptophan Threonine Isoleucine Methionine Histidine Arginine Leucine Lysine
When does the Urea Cycle occur?
When there are excess AA’s in the diet. Under starvation conditions and protein breakdown. Occurs in liver and kidney.
How does the urea cycle begin?
Most aa’s will react with AKG via transamination to create their alpha ketoacid and Glutamate.
This glutamate will travel to the liver and release the NH3 (regenerating AKG) via Glutamate Dehydrogenase.
Glutamate Dehydrogenase
Helps glutamate release NH3 in liver. Glu becomes AKG.
How are Ser Thr, Cys, His metabolized?
They create NH3 in muscles. So this NH3 is attached to Glutamate using ATP via Glutamine Synthase. Glutamine then travels to the liver, where glutaminase disassembles it back into glutamate and NH3.
Urea Cycle reaction
In Liver Mitochondria:
HCO3 + NH3 –> Carbamoyl Phosphate (using 2 ATP’s via Carbamoyl Phosphate Synthetase AKA CPS1).
Carbamoyl Phosphate + Ornithine —> Citrulline (via ornithine transcarbamoylase).
Citrulline migrates out of mitochondria and + aspartate –> argininosuccinate (using ATP-> AMP via argininosuccinate synthetase).
Argininosuccinate –> Arginine + Fumarate (via argininosuccinate lyase).
Fumarate goes to the TCA cycle.
Arginine + H2O –> Urea + Ornithine (via arginase).
How many times does glutamate feed into the urea cycle?
Twice.
1) By donating its NH3, which is used in step one of the urea cycle.
2) By undergoing transamination with OAA to create aspartate, which combines with citrulline to form argininosuccinate.
How is NH3 overdose treated?
Eliminate glycine using benzoate or eliminate glutmate using phenylacetate.
GOT
Glutamic Oxoacetic Transaminase. Catalyzes Asp + AKG –> OAA + Glu.
GPT
Glutamic Pyruvate Transaminase. Catalyzes Alanine + AKG –> Pyruvate + Glutamate
