Biochemistry-Nitrogen Metabolism Flashcards
Kwashiorkor
Protein deficiency and reduced synthesis of serum albumin results in abdominal edema.
If you are starving in the forest and you kill a jackrabbit what parts of the jackrabbit should you eat?
Everything. Eating a protein only diet will give you jackrabbit fever. You must also have fat in your diet.
How is nitrogen stored in the body?
It isn’t, all excess nitrogen is excreted mainly as urea, some is excreted as uric acid and creatine phosphate.
What is the source of nitrogen for neurotransmitters during the fasting state?
Skeletal muscle
What process drops nitrogen off at the liver on its way to run another errand?
During the fasted state, muscle breaks down protein to alanine -> alanine goes to the liver, drops nitrogen off for conversion to urea and secretion and the carbon backbone is converted to pyruvate turned into glucose via gluconeogenesis.
What helps to neutralize acidosis caused by ketoacids during the fasted state?
Muscle protein is degraded to glutamine, glutamine goes to the kidney and releases two NH3, both NH3 molecules pick up a H+ in the urine and are excreted at NH4+. This buffers the ketoacids.
What breakdown product of protein is found in high concentrations in the gut?
Glutamine. The enterocytes are turning over so rapidly that they are synthesizing new DNA at high rates. You need glutamine to synthesize DNA.
How is excess nitrogen package in the muscle so it can be sent to the liver?
alpha-ketoglutarate + NH4+ -> glutamate by the enzyme glutamate DH. Glutamate + NH4+ -> Glutamine by the enzyme glutamine synthetase.
Where do the nitrogens in this molecule come from?
NH3 and aspartic acid are the main nitrogen donors to the urea cycle.
What are the advantages of excreting urea?
Non-toxic, water soluble and it combines 2 waste products into one molecule (CO2 and two NH3 molecules)
Why is ammonium so nasty?
Charged NH4+ cannot cross membranes. However, it is in equilibrium with NH3 that can go anywhere in the body. Once ammonia gets to the other side of a membrane it equilibrates with NH4+ again.
1st, 2nd and 3rd steps in disposing of nitrogen
1) Transamination taking amino acid nitrogen to alpha-ketoglutarate to form glutamate. 2) Transamination reaction taking glutamate to alpha-ketoglutarate and OAA to aspartate 3) Oxidatitve deamination of glutamate to alpha-ketoglutarate by glutamate dehydrogenase to form NH4+
What produces the majority of NH4+ that will enter the urea cycle?
His, Ser and Thr undergo elimination reactions. Gln and Asn under hydrolysis (glutaminase and asparaginase) reactions w/reversible reactions (glutamine synthase and asparagine synthase) for shuttling of NH4+ across tissue. Bacteria also produce NH4+ in the gut.
Summarize the sources of ammonia for the urea cycle
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What is the key reaction that drives the urea cycle?
Hydrolysis of arginine by arginase.
How do you go from amines to amides?
Add water across a carboxylic acid and amine to form the amide. Note that this bond can go the other way and is hydrolyzable.
How do you form a Schiff base?
Condensation reaction between an amine and a ketone. Note that this bond can go the other way and is hydrolyzable.
What is the 1st chemical reaction in the urea cycle?
Cabamoylation. An amine attacks the carbon of an activated carbamoyl phosphate to form a ureido and a phosphate.
How do you form urea?
2 NH3 molecules + carbonic acid, take away water and form urea.
How do you form the guanidinium group?
Urea + amine and a condensation reaction forms the Schiff base that is actually the side chain of arginine. Note that this reaction can go in reverse by hydrolysis.
What is the key chemical reaction in the urea cycle?
Arginine + water and the enzyme arginase gives you ornithine (note that it is like lysine but 1C shorter) and urea.
Where does the NH4+ that comes from aspartate generate in the cell? What other organelle contributes NH4+?
Cytosol. NH4+ is also produced in the mitochondria.
Beginning steps of the urea cycle that start in the mitochondria
CO2 + H2O form HCO3-. HCO3- combines with NH4+ by the action of carbamoyl phosphate synthetase I (CPSI) and 2 ATPs to form carbamoyl phosphate. Carbamoyl phosphate reacts with ornithine by the enzyme ornithine transcarbamoylase to form citrulline (ornithine w/a carbamoyl group on the side chain).
How does citrulline get out of the mitochondrial matrix? What does it do from there?
There is a citrulline/ornithine antiporter. Citrulline then forms a Schiff base with aspartate via the enzyme argininosuccinate synthetase + ATP to form argininosuccinate.
