protein breakdown and urea formation Flashcards
(19 cards)
what is nitrogen balance?
→ 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?
→ the carbon skeleton
→ nitrogen
→The 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?
→Nitrogen is toxic, so it has to be removed safely.
→ 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?
→transamination
→ formation of ammonia
→formation of urea
describe transamination
→chemical reaction that transfers an amino group to a keto acid to form new amino acids.
→Transaminase (aka aminotransferases) is the enzyme involved in this reaction.
→It catalyses a transamination reaction between an amino acid and a α-keto acid.
→The nitrogen group of one amino acid is transferred to a particular keto acid to give us a second amino acid.
→The synthesised molecules can be metabolised more readily.
what are some alpha keto acids and what can they be oxidized to?
→ α-ketoglutarate
→pyruvate
→oxaloacetate
→α-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?
→ALANINE (ALT) Alanine will react with α-ketoglutarate to give pyruvate and glutamate.
→In the context of urea formation, this reaction predominates.
→ASPARTATE (AST) Aspartate will react with α-ketoglutarate to give oxaloacetate and glutamate.
→In the context of urea formation, the opposite of this reaction predominates.
→Both generate glutamate, and both reactions are fully reversible.
→These reactions require pyridoxal phosphate derived from Vit B6.
how can the levels of transaminases be used diagnostically?
→Transaminases are primarily liver enzymes, so high levels of ALT and AST in the blood can be indicative of liver damage
→they’re not meant to be released into circulation
what happens to the glutamate after transamination?
→Glutamate can release ammonia directly by the action of glutamate dehydrogenase.
→The 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 α-ketoglutarate of amino acids important ?
→ conversion of many amino acids from their original state into glutamate
→ can be transported and then re-converted back into something the body can use for energy (or transamination again)
→ re-synthesizing the ammonia that is fed into the urea cycle
how do we eliminate free ammonia?
→Free ammonia generated in tissue combines with Glutamate to give Glutamine.
→Glutamate + NH4+ + ATP –> Glutamine + ADP
→This reaction is catalysed by Glutamine Synthase.
what is the importance of glutamine in the transport of nitrogen?
→Glutamine is the main transporter of nitrogen.
→ formed from glutamate which, in addition to having already accepted amino-groups to α-ketoglutarate, accepted more nitrogen to form glutamine.
→Glutamine can donate nitrogen for the biosynthesis of amino acids, nucleotides, amino sugars and NAD+.
describe the structure of urea
→Urea is made up of two amine groups joined to a C=O.
→One amine group is donated from aspartate, while the other comes from glutamine/glutamate.
→The carbon C=O comes from the carbon skeleton, through using CO2 that has been produced from its breakdown.
→detrimental 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
→CO2 comes from the bicarbonate and reacts with the ammonium ion that has come from glutamine/glutamate (formed by transamination of α-ketoglutarate and α-amino acid).
→They form carbamoyl phosphate (in the mitochondria). Carbamoyl phosphate then reacts with Ornithine to produce Citrulline.
→Citrulline reacts with Aspartate to form Argininosuccinate.
→ Argininosuccinate then is metabolised to Arginine (urea cycle) and Fumarate (TCA).
→The Arginine is acted upon by the enzyme arginase which is how urea is formed.
→The urea cycle continues.
→ Fumarate is converted to Malate which is transported back into the mitochondria and converted into oxaloacetate.
→The TCA then continues.
how are muscles involved in the breakdown of amino acids?
→Muscles don’t have the enzymes needed to form urea, so the urea cycle doesn’t take place in muscles.
→muscles 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?
→1) Nitrogen is transferred to alanine (via glutamate and pyruvate)
→2) Circulating/intracellular glutamate can be made into glutamine (and return to the liver)
how do muscles come into the removal of nitrogen?
→muscle 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
→In the muscle, branched amino acids are taken and broken down.
→The carbon skeleton is used for energy production.
→ the NH4 can be used to convert to pyruvate to Alanine. Alanine is then exported into the blood and travels to the liver.
→ alanine is then converted to glutamate via transamination (reacting with α-ketoglutarate) also producing a pyruvate.
→The 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.
→The glutamate will then be used along with the CO2 generated to produce urea in the liver.
why is glutamate a useful molecule?
→Glutamate is a very useful molecule
→ freely interchangeable with the α-keto acids
→ability to donate and accept ammonium ions.
