Protein breakdown and urea formation Flashcards
What is positive nitrogen balance?
Too much nitrogen input
What is negative nitrogen balance?
To little nitrogen input
What are the two parts of the metabolism of amino acids?
The carbon skeleton
Nitrogen
What happens to amino acids?
They aren’t stored, they’re used or broken down
what is the carbon skeleton from the metabolism from amino acids used for?
Used for:
Energy metabolism
Biosynthetic pathways
Why has nitrogen got to be removed?
Nitrogen is so toxic so has to be removed safely
How is nitrogen removed in mammals?
In mammals, nitrogen converted to the non-toxic neutral compound urea and excreted in the urine
What is the enzyme involved in the first step in the transfer of amino acid nitrogen to urea (transamination)?
Enzyme involved in transaminase
What happens in transamination?
Nitrogen group of amino acid A transferred to keto acid B give to second amino acid B and Keto acid A
Why are keto acid important in transamination?
Keto acids are important metabolic intermediates
Examples of transaminase
Alanine and Aspartate
What does alanine form when catalysed with alpha ketoglutarate?
Alanine catalyses α-ketoglutarate to give pyruvate and glutamate
What does aspartate form when catalysed with alpha ketoglutarate?
Aspartate catalyses α-ketoglutarate to give oxaloacetate and glutamate
What are high levels of alanine and aspartate indicative of?
High levels of alanine and aspartate in the blood are indicative of liver damage
What does transamination reaction require?
Whole reaction requires pyridoxal phosphate derived from vitamin B6
In the second step of transfer of amino acid nitrogen to urea(oxidative deamintation), what is glutamate converted into and by what?
Glutamate can be converted to α-ketoglutarate by glutamate dehydrogenase
What type of reaction is the conversion of glutamate to alpha ketoglutarate and what is used?
Fully reversible and can either use NAD or NADP
What else is formed in oxidative deamination, other than alpha ketoglutarate?
Ammonia is also formed and is the substrate to the urea cycle
How is glutamine synthesised and why is it needed?
○ Elimination of free ammonia:
§ Glutamate gains nitrogen from ammonia
§ ATP and glutamine synthase involved
Glutamine main transporter of nitrogen as it is readily soluble
In step 3 of the transfer of amino acid nitrogen to urea(urea formation), what is the means of this step?
Means of excreting nitrogen
Where are the enzymes present for urea formation and where are they not?
Present in liver but not muscle
Where does urea formation occur?
Takes place in mitochondria and cytoplasm
What are the substrates involved in urea formation?
Substrates are bicarbonate, aspartate and ammonium ions(released from either glutamine or glutamate)
How many amnio groups are used in the formation of urea and where do they come from?
○ Formation of urea uses two amino groups
One from glutamate and one from aspartate
How does the urea cycle interact with the tricarboxylic acid cycle?
- Ammonia first reacts to form carbamoyl phosphate
- Combines with ornithine to give citrulline
- Citrulline breaks down to give arginine which under the influence of arginase gives urea
- Fumarate converted to malate and then oxaloacetate
What is formed when oxaloacetate further reacts with an amino acid?
Oxaloacetate Can be used to react with further amino acid to give a keto acid and asparate
What is used for energy in muscles during prolonged exercise or starvation?
In prolonged exercise or starvation, branched amino acids are used for energy
What enzymes are not present in muscles?
Enzyme of the urea cycle not present
What are the two routes of transport to transport nitrogen to liver from muscle?
○ Alanine
§ Nitrogen transferred to alanine via glutamate and pyruvate
○ Glutamine
Glutamate is made into glutamine
What are the steps involved in the glucose alanine cycle?
• Break down of protein
• Transamination to form alanine
• Alanine reacts to form glutamate and pyruvate
Glutamate synthesises urea
What happens to the carbon skeleton formed in the glucose alanine cycle?
• Carbon skeleton that is formed is converted to pyruvate
What is the fate of the carbon skeleton
Will form α-keto acids. Some of the backbone of other amino acids can also feed into different components of the TCA cycle
What amino acids are the only ones which cannot inter-convert into alpha keto acids?
lysine and threonine
What is normal metabolism after a meal for a healthy individual in terms of insulin and glucagon levels?
High insulin
Low glucagon
In normal metabolism after a meal, what happens to most amino acids?
Most amino acids from a protein meal used for protein synthesis in peripheral tissues such as skeletal muscle
In normal metabolism after a meal, what happens to excess amino acids?
Excess amino acids used as sources of energy and nitrogen derived from their oxidation is incorporated into urea in the liver and excreted
In normal metabolism during starvation, what are the insulun a glucagon levels like?
Insulin is low
Glucagon is high
In normal individual during short term starvation, where is the net flow of amino acids and production of what is increased?
§ Net flow of amino acids from muscle to liver
Increased production of glucose and urea
In normal individual during long term starvation, what happens to tissue proteins?
Tissue protein is spared because ketone bodies replace glucose as major energy fuel for the brain
What is the nitrogen balance in untreated diabetes and why?
Negative nitrogen balance due to decreased protein synthesis or increased protein breakdown
When is negative nitrogen balance seen?
Seen in conditions like chronic infections, late stage cancer or trauma
What are some of the effects in negative nitrogen balance mediated by?
Some of these effects are mediated by cytokines
