Protein Breakdown & Urea Formation

Question 1

what is nitrogen balance?

Answer 1

= N input - N output

Question 2

what are the 2 parts of the aa and how is the carbon skeleton broken down?

Answer 2

• carbon skeleton, nitrogen

- broken down by energy metabolism and biosynthetic pathways

Question 3

why do we need to remove nitrogen and what is it converted into to be removed?

Answer 3

• N is toxic

- in mammals, converted to urea (safe) and excreted in urine

Question 4

what are the 3 steps in which aa N is transferred to urea?

Answer 4

• transamination
• formation of ammonia
• formation of urea

Question 5

describe transamination

Answer 5

• 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

Question 6

what are some α-keto acids and what can they be oxidised to?

Answer 6

• α-ketoglutarate
• pyruvate
• oxaloacetate
• α-keto acids are important metabolic intermediates: can be oxidised or converted to glucose

Question 7

what are 2 important aminotransferases and what chemical reactions do they catalyse?

Answer 7

-alanine (ALT) and aspartate (AST) transaminase

• ALT reacts to form pyruvate
• AST forms oxaloacetate

Question 8

how can the levels of transaminase bemused diagnostically?

Answer 8

-transaminases primarily in liver so high ALT and AST in blood indicative of liver damage as they aren’t to be released into circulation

Question 9

how is ammonia released (formed)?

Answer 9

-oxidative deamination

glutamate releases ammonia by the action of glutamate dehydrogenase

glutamate —> α-ketoglutarate (with release of NH3)

Question 10

why is having the transamination to glutamate and then oxidative deamination back to α-ketoglutarate of aa important?

Answer 10

• 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

Question 11

where does oxidative deamination occur?

Answer 11

mitochondrial matrix

Question 12

what happens to the NH3 released from oxidative deamination?

Answer 12

fed into urea cycle

Question 13

how is free NH3 eliminated?

Answer 13

• free NH3 combines w glutamate to give glutamine
• glutamine v soluble and really transported in blood

glutamate + NH4+ + ATP —-> glutamine + ADP

Question 14

what is the importance of glutamine in the transport of N?

Answer 14

• glutamine main transporter of N

- can donate N for biosynthesis of aa, nucleotides, amino sugars and reduced NADH

Question 15

describe the structure of urea

Answer 15

• 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

Question 16

describe the urea cycle

Answer 16

-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

Question 17

how muscles involved in the breakdown od aa?

Answer 17

• 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

Question 18

what are the 2 ways remaining aa are dealt with in the muscle?

Answer 18

1) N transferred to alanine via glutamate and pyruvate

2) circulating/intracellular glutamate can be made into glutamine and return to liver

Question 19

how do muscles come into the removal of N?

Answer 19

-can export alanine as it is the major exports of muscle that is actively being broken down

Question 20

describe the glucose-alanine cycle between the muscle and liver

Answer 20

• 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

Question 21

why is glutamate a useful molecule?

Answer 21

• freely interchangeable w α-keto acids

- ability to donate and accept NH4+