Disposal Of Amino-nitrogen From The Catabolism Of Amino Acids

Question 0

What is the fate of carbon from amino acids?

Answer 0

Major fat in high protein diets is energy and gluconeogenesis for glucose homeostasis
-major fate during starvation is gluconeogenesis for glucose homeostasis.
Note: need to remove amino-N before the carbon skeleton is useful for energy

Question 1

To break amino acids down and utilise their carbon backbone you have to remove the amine (N) group.
With this free carbon back bone you can now, use it for energy, make glucose out of it (starvation).
In a high protein intake with adequate levels of carbs you will just gain fat or if there isn’t enough carbs you will use them for glucose.

Answer 1

H

Question 2

Describe what the glucogenic, glucogenic/ketogenic and ketogenic aa are?

Answer 2

Glucogenic: aa that have n group removed and can feed into TCA cycle then into gluconeogenesis.

Glucogenic and ketogenic: they release both a carbon backbone that is a TCA cycle intermediate which feeds into gluconeogenesis and an acetyl coA which feeds into ketogenesis.

Ketogenic: short aa, only end up with acyl CoA,

Classifying depending on end point.

Question 3

Removal of amino-nitrogen from amino acids. How?

What are the key enzymatic players?

Answer 3

There a few enzymatic key players.
Transamination; all tissues but mainly liver
-alanine transaminase- it grabs a pyruvate and steals the amine group from another amino acid, it will then put this amine group on the pyruvate then end up with alanine.
-aspartate transaminase: starts with oxaloacetate, steals an amine group from someone then end up with aspartate
-glutamate transaminase: grabs a-ketogluterate, robs someone else of their amine group, you end up with glutamate.
-these guys just swap the amine group around
Direct deamination:
-glutamate dehydrogenase (liver)
-glutaminase (kidney and liver)
-these guys directly cleave the amine group of and release free aa.
All high Km enzymes.

Question 4

Check out slides 13-15

Answer 4

Haven’t written it down

Question 5

This is all well and good except Ammonia is toxic to the CNS. Explain

Answer 5

NH3 (present as the ammonium ion) (NH4) at physiological PH must be cleared from both the bloodstream and intra-cellularly to prevent neural toxicity.
What ya do with it?
-you form urea (non toxic), which is synthesis used in the LIVER transported in the blood excreted by the KIDNEY by urine.

Question 6

Urea cycle: detoxifies NH3
Energy cost? 
Occurs wear? 
Key enzyme 
Carrier of N?

Answer 6

Energy cost is 4 ATP per molecule
Occurs in the liver only
Key enzyme: Arginase is key for urea synthesis
Ornithine is the carrier of N

Question 7

How is the urea cycle regulated?

Answer 7

• enzymes of urea cycle are controlled at gene level
• when dietary proteins are increased, enzyme concentrations rise
• balanced diet, enzyme levels decline
• starvation, enzyme levels rise as proteins are degraded and amino acid carbon skeletons are used to provide energy, thus more nitrogen is excreted.

Short term regulation:

• occurs primarily at Carbamoyl phosphate synthetase 1.
• this enzyme conc increases when your starving or on a high protein diet.
• also allosterically stimulated by N-acetyl glutamate.
• the amount of N-acetyle glutamate is determined by the concentration of its components acetyle CoA and glutamate.
• arginine is s positive allosteric effector of N-acetyl glutamate synthetase which increases it production.

Question 8

We’re do we get the nitrogen for our urea cycle From?

Answer 8

• Aspartate donates amine group
• glutamate through action of glutamate dehydrogenase
• glutamine

All the other aa try to get channeled into these 3 above. How?
Through the transaminase enzymes which robs an amino acid and makes it into the above. Done so we can dispose of their nitrogen

Question 9

Nitrogen transport systems.

Glutamine

Answer 9

-Synthesised by glutamine synthetase from glutamate and NH3 using ATP as energy source
-glutamine transports amino-N from extra hepatic tissues to the liver for disposal of N as urea via hepatic glutaminase.
slide 35
Slide 36 has summary of all NH3 transport.

Glutamine also transports amino-N to the kidney and the amino-N lost as ammonia via renal glutaminase directly into the urine.
-mechanism or direct nitrogen excretion

Question 10

Tell me about the glucose alanine cycle.

Answer 10

process for collecting amino-N and carbon from muscle and other extra hepatic tissues and transferring carbon and nitrogen to the liver via the blood
3 main tissues: muscle, blood and liver
-alanine is formed from pyruvate at a rate that is proportional to intracellular pyruvate levels.
-liver accumulates plasma alanine, reverses the transamination that occurs in the muscle and proportionately increases urea production.
-the pyruvate is either oxidised or converted to glucose.
When alanine transfer from the muscle to the liver is coupled with glucose transported from the liver to the muscle, process is known as glucose alanine cycle.