BIOC L8 - nitrogen metabolism III

What is urea?

synthesised in the liver and maintains nitrogen in a soluble and non toxic form

How is urea synthesised and then excreted?

liver takes up excess nitrogen in the form of glutamate and aspartate, urea travels ot the kidney for excretion and eliminates 2 nitrogens

What are the 2 things that nitrogen can enter the urea cycle in?

carbamoyl phosphate and aspartate

What is carbamoyl phosphate?

synthesised from bicarbonate and ammonia, requires carbomoyl phosphate synthetase

How does nitrogen enter the urea cycle as aspartate?

aspartate is generated from transamination of glutamate+oxaloacetate -> aKG+aspartate

How is the urea cycle regulated?

carbamoyl phosphate synthetase enzyme which begins to be synthesised in a high protein diet or ine arly stage sof starvation when body proteins are broken down and there is more nitrogen that needs to be dealt with

What reduces the activity of the urea cycle?

liver disease

How is CPS activity regulated?

allosterically regulated by N-acetylglutamate which is formed when acetylcoa and glutamate present in high protein diet and in early stages of starvation

What characterises urea cycle enzyme disorders and what are the treatment options?

main symptom is hyperammonemia which affects the brain, the best treatment is dietary intervention maintaining energy but decreasing protein intake but can also treat with amino acid binding compounds such as phenylbutyrate

What does phenylbutyrate do?

an amino acid binding compound which picks up extra N and excretes it safely as phenylaceylglutamine for people with urea cycle enzyme disorders

What is ammonia toxicity in the brain do?

NH4+ can inhibit post synaptic potentials, depletion of CAC intermediates for ETC reducing ATP, glutamine accumulation in astrocytes, generate inappropriate levels of neurotranmitters etc leading to passing out due to neuron inactivity or seziures due to neuron hyperactivity

How does NH4+ leave the kidney proximal tube cells into the lumen of the tubule?

as NH3 and Na+ and reform NH4+ in the lumen