Protein Breakdown & Urea Formation Flashcards
what is nitrogen balance?
= N input - N output
what are the 2 parts of the aa and how is the carbon skeleton broken down?
- carbon skeleton, nitrogen
- broken down by energy metabolism and biosynthetic pathways
why do we need to remove nitrogen and what is it converted into to be removed?
- N is toxic
- in mammals, converted to urea (safe) and excreted in urine
what are the 3 steps in which aa N is transferred to urea?
- transamination
- formation of ammonia
- formation of urea
describe transamination
- chemical reaction that transfers an amino group to a ketogenic acid to form new aa
- transaminase is enzyme involved
- N group of one aa transferred to particular ketogenic acid to give second aa
- synthesised molecules can be metabolised more readily
aa A + α-keto acid B –> aa B + α-keto acid A
what are some α-keto acids and what can they be oxidised to?
- α-ketoglutarate
- pyruvate
- oxaloacetate
- α-keto acids are important metabolic intermediates: can be oxidised or converted to glucose
what are 2 important aminotransferases and what chemical reactions do they catalyse?
-alanine (ALT) and aspartate (AST) transaminase
- ALT reacts to form pyruvate
- AST forms oxaloacetate
how can the levels of transaminase bemused diagnostically?
-transaminases primarily in liver so high ALT and AST in blood indicative of liver damage as they aren’t to be released into circulation
how is ammonia released (formed)?
-oxidative deamination
glutamate releases ammonia by the action of glutamate dehydrogenase
glutamate —> α-ketoglutarate (with release of NH3)
why is having the transamination to glutamate and then oxidative deamination back to α-ketoglutarate of aa important?
- conversion of aa to glutamate means it can be transported and reconverted to something useful for body
- resynthesising the ammonia that is fed into urea cycle
where does oxidative deamination occur?
mitochondrial matrix
what happens to the NH3 released from oxidative deamination?
fed into urea cycle
how is free NH3 eliminated?
- free NH3 combines w glutamate to give glutamine
- glutamine v soluble and really transported in blood
glutamate + NH4+ + ATP —-> glutamine + ADP
what is the importance of glutamine in the transport of N?
- glutamine main transporter of N
- can donate N for biosynthesis of aa, nucleotides, amino sugars and reduced NADH
describe the structure of urea
- made of 2 amine groups joined to a C=0
- one amine group donated from aspartate, while other from glutamine/glutamate
- C=O from carbon skeleton
describe the urea cycle
-CO2 comes from bicarbonate and reacts w NH4+
-forms carbamoyl phosphate in mito
-carbamoyl phosphate reacts w ornithine to produce citrulline
=citrulline reacts w aspartate to form arginine-succinate
-arginine-succinate is metabolised to arginine (urea cycle) and fumarate (TCA)
- arginine acted on by arginase which forms urea
- urea cycle continues
- fumarate converted to malate which is transported into mito and converted into oxaloacetate
- TCA cycle continues
how muscles involved in the breakdown od aa?
- muscles dont have the enzymes needed to form urea so urea cycle doesn’t happen in muscles
- NH4+ need to be transported to liver by alanine or glutamine
- muscles do break down aa for energy during prolonged exercise or starvation
what are the 2 ways remaining aa are dealt with in the muscle?
1) N transferred to alanine via glutamate and pyruvate
2) circulating/intracellular glutamate can be made into glutamine and return to liver
how do muscles come into the removal of N?
-can export alanine as it is the major exports of muscle that is actively being broken down
describe the glucose-alanine cycle between the muscle and liver
- in muscle, branched aa taken and broken down
- carbon skeleton is used for energy production
- the NH4+ converted to pyruvate to alanine
- alanine transported into blood and travels to liver
- alanine converted to glutamate via transamination to produce pyruvate
- pyruvate can enter gluconeogenic pathway to form glucose
- glucose can then be used for energy
why is glutamate a useful molecule?
- freely interchangeable w α-keto acids
- ability to donate and accept NH4+
