protein breakdown and urea formation Flashcards
what is nitrogen balance?
β Nitrogen balance is a measure of nitrogen input minus nitrogen output.
what are the two parts of an amino acid and how is the carbon skeleton broken down?
β the carbon skeleton
β nitrogen
βThe carbon skeleton is broken down by energy metabolism and biosynthetic pathways.
why do we need to remove nitrogen, and what is it converted into to be removed?
βNitrogen is toxic, so it has to be removed safely.
β In mammals, the nitrogen is converted to the non-toxic, neutral compound urea and excreted in urine.
what are the three steps in which amino acid nitrogen is transferred to urea?
βtransamination
β formation of ammonia
βformation of urea
describe transamination
βchemical reaction that transfers an amino group to a keto acid to form new amino acids.
βTransaminase (aka aminotransferases) is the enzyme involved in this reaction.
βIt catalyses a transamination reaction between an amino acid and a Ξ±-keto acid.
βThe nitrogen group of one amino acid is transferred to a particular keto acid to give us a second amino acid.
βThe synthesised molecules can be metabolised more readily.
what are some alpha keto acids and what can they be oxidized to?
β Ξ±-ketoglutarate
βpyruvate
βoxaloacetate
βΞ±-keto acids are important metabolic intermediates. They can be oxidised or converted to glucose.
what are two important aminotransferases and what are the chemical reaction that they catalyze?
βALANINE (ALT) Alanine will react with Ξ±-ketoglutarate to give pyruvate and glutamate.
βIn the context of urea formation, this reaction predominates.
βASPARTATE (AST) Aspartate will react with Ξ±-ketoglutarate to give oxaloacetate and glutamate.
βIn the context of urea formation, the opposite of this reaction predominates.
βBoth generate glutamate, and both reactions are fully reversible.
βThese reactions require pyridoxal phosphate derived from Vit B6.
how can the levels of transaminases be used diagnostically?
βTransaminases are primarily liver enzymes, so high levels of ALT and AST in the blood can be indicative of liver damage
βtheyβre not meant to be released into circulation
what happens to the glutamate after transamination?
βGlutamate can release ammonia directly by the action of glutamate dehydrogenase.
βThe reaction is fully reversible and can use either NAD or NADP; however, it is usual for NAD to be used for degradation and NADPH for synthesis.
why is having the transamination to glutamate and then the oxidative deamination back to Ξ±-ketoglutarate of amino acids important ?
β conversion of many amino acids from their original state into glutamate
β can be transported and then re-converted back into something the body can use for energy (or transamination again)
β re-synthesizing the ammonia that is fed into the urea cycle
how do we eliminate free ammonia?
βFree ammonia generated in tissue combines with Glutamate to give Glutamine.
βGlutamate + NH4+ + ATP β> Glutamine + ADP
βThis reaction is catalysed by Glutamine Synthase.
what is the importance of glutamine in the transport of nitrogen?
βGlutamine is the main transporter of nitrogen.
β formed from glutamate which, in addition to having already accepted amino-groups to Ξ±-ketoglutarate, accepted more nitrogen to form glutamine.
βGlutamine can donate nitrogen for the biosynthesis of amino acids, nucleotides, amino sugars and NAD+.
describe the structure of urea
βUrea is made up of two amine groups joined to a C=O.
βOne amine group is donated from aspartate, while the other comes from glutamine/glutamate.
βThe carbon C=O comes from the carbon skeleton, through using CO2 that has been produced from its breakdown.
βdetrimental products of amino acid degradation can be used to combine to form urea, a non-toxic, soluble compound that can be readily excreted.
describe the urea cycle
βCO2 comes from the bicarbonate and reacts with the ammonium ion that has come from glutamine/glutamate (formed by transamination of Ξ±-ketoglutarate and Ξ±-amino acid).
βThey form carbamoyl phosphate (in the mitochondria). Carbamoyl phosphate then reacts with Ornithine to produce Citrulline.
βCitrulline reacts with Aspartate to form Argininosuccinate.
β Argininosuccinate then is metabolised to Arginine (urea cycle) and Fumarate (TCA).
βThe Arginine is acted upon by the enzyme arginase which is how urea is formed.
βThe urea cycle continues.
β Fumarate is converted to Malate which is transported back into the mitochondria and converted into oxaloacetate.
βThe TCA then continues.
how are muscles involved in the breakdown of amino acids?
βMuscles donβt have the enzymes needed to form urea, so the urea cycle doesnβt take place in muscles.
βmuscles do break down amino acids for energy during prolonged exercise or starvation.
what are the two ways in which remaining amino acids are dealt with in the muscle?
β1) Nitrogen is transferred to alanine (via glutamate and pyruvate)
β2) Circulating/intracellular glutamate can be made into glutamine (and return to the liver)
how do muscles come into the removal of nitrogen?
βmuscle can export alanine, as it is one of the major exports of muscle that is actively being broken down (due to exercise or starvation).
describe the glucose-alanine cycle between the muscle and the liver
βIn the muscle, branched amino acids are taken and broken down.
βThe carbon skeleton is used for energy production.
β the NH4 can be used to convert to pyruvate to Alanine. Alanine is then exported into the blood and travels to the liver.
β alanine is then converted to glutamate via transamination (reacting with Ξ±-ketoglutarate) also producing a pyruvate.
βThe pyruvate can enter the gluconeogenic pathway to form glucose, and the glucose can be transported in the blood back to the muscle where it can be used for energy.
βThe glutamate will then be used along with the CO2 generated to produce urea in the liver.
why is glutamate a useful molecule?
βGlutamate is a very useful molecule
β freely interchangeable with the Ξ±-keto acids
βability to donate and accept ammonium ions.
