Lecture 7 - Nitrogen Metabolism Part 3

Question 1

what is the main carrier of nitrogen from muscle to liver

Answer 1

alanine

Question 2

why must ammonia levels stay low

Answer 2

it is toxic, especially for the brain

Question 3

where is urea synthesised

Answer 3

in the liver

Question 4

the liver will take up excess NH3 in the form of what

Answer 4

alanine and glutamine

Question 5

how and where is urea transported to for excretion

Answer 5

transported in the blood to the kidneys for excretion

Question 6

how does urea reduce the toxicity cause by ammonia

Answer 6

it maintains N in a soluble, non toxic form

(urea = non toxic, ammonia = toxic)

Question 7

what are the two ways that nitrogen enters the urea cycle

Answer 7

carbamoyl phosphate and aspartate

Question 8

what is carbamoyl phosphate is synthesised from

Answer 8

synthesised from bicarbonate and ammonia

Question 9

what does ammonia come from

Answer 9

the deamination of glutamine and glutamate

Question 10

what kind of reaction forms carbamoyl phosphate and what is it catalysed by

Answer 10

Energy requiring reaction catalysed by carbamoyl phosphate synthetase

Question 11

what is aspartate generated by

Answer 11

transamination

Question 12

where is oxaloacetate formed that is used to produce aspartate

Answer 12

in the citric acid cycle

Question 13

where do the first two reactions of the urea cycle occur

Answer 13

in the mitochondria

Question 14

where do the rest of the reactions apart from the first two of the urea cycle occur

Answer 14

in the cytosol

Question 15

where is arginine made

Answer 15

in the urea cycle, it is the non essential and essential amino acid

Question 16

what is the major point of regulation of the urea cycle

Answer 16

carbamoyl phosphate synthetase (CPS) activity

Question 17

when is carbamoyl phosphate synthetase (CPS) activity upregulated

Answer 17

under conditions of high protein diet or early stages of fasting / starvation

Question 18

when can urea cycle activity by reduced

Answer 18

liver disease e.g cirrhosis

Question 19

how is carbamoyl phosphate synthetase regulated and what does this mean

Answer 19

allosterically regulated

• the activity of the enzyme is regulated by the binding of a molecule to the enzyme that is not the active site

Question 20

what is the allosteric regulator that binds to carbamoyl phosphate synthetase to activate it

Answer 20

N - acetylglutamate

Question 21

in what situations will N - acetylglutamate be made

Answer 21

situations of high glutamate and Acetyl-CoA

Question 22

what are the phenotypes of disorders to the urea cycle

Answer 22

Variety of phenotypes (mainly neurological - brain issues and all involve hyperammonemia)

Question 23

how to treat disorders of the urea cycle enzymes

Answer 23

• by dietary modification i.e limit the protein in the presence of sufficient calories
• With amino acid-binding compounds i.e. phenylbutyrate

Question 24

what does a defect to an enzyme in the urea cycle cause

Answer 24

• build up of ammonia, which is very toxic
• high levels of ammonia found in the blood leads to brain issues and lethargicness

Question 25

can defects to the urea cycle enzymes be inherited

Answer 25

yes

Question 26

what enzyme is the most common to have a defect in the urea cycle

Answer 26

OTC

Question 27

what gender is a defect to OTC more likely in and why

Answer 27

more likely in males because it is on X chromosome

Question 28

in the brain what may NH4+ inhibit

Answer 28

post synaptic potentials

Question 29

what does depletion of citric acid cycle intermediates mean for the brain

Answer 29

decreased ATP for brain function

Question 30

accumulation of glutamine in astrocytes causes what and why

Answer 30

increases osmotic pressure cerebral oedema

• as glutamine is osmotic type compound, water will follow it and can cause swelling in the brain)

Question 31

how does phenylbutyrate assist the clearance of nitrogen waste

Answer 31

the drug is rapidly converted to phenylacetate, which combines with glutamine to form phenylacetylglutamine

this contains two nitrogen atoms and is excreted so increases the clearance of nitrogen waste

Question 32

how is NH4+ produced in the kidneys

Answer 32

by deamination of glutamine

Question 33

in the process of ammonia being excreted into urine, ammonia is released in the epithelial cell in what form and what from

Answer 33

ammonia is released in the protonated form from glutamine and glutamate

Question 34

before NH4+ is pumped from the epithelial cell into the lumen what happens to it

Answer 34

proton is split from NH4+ to form NH3

Question 35

what allows NH3 to be pumped into the lumen and enter the urine

Answer 35

The sodium proton exchange allows protons to be pumped into the lumen

Question 36

the kidney can utilise a-ketoglutarate to produce what

Answer 36

produce glucose