Scenarios 9/04

Question 0

Starvation

Answer 0

-body will start mobilising body protein. What regulates it? Glucagon. How? It accelerated the lysosomal degredation pathway. What slows its down? Insulin.
-after this there is big influx of proteins into pool so concentration increases. This accelerates rate of deamination (removal of that nitrogen). What regulates deamination pathways➡ transaminase, glutamate dehydrogenase etc what regulates these? Concentration!
Once your concentration levels of aa in pool increase deamination begins brutha! Coz its relatively high Km.
so you will get some glucose synthesis, some energy production and nitrogen will be disposed of through urea cycle.

Question 1

Glycine

Tell me how it is synthesised

Answer 1

A good model for demonstration of anabolic and catabolic fates of amino acids.
Tell me about glycine synthesis.
Serine coupled with serine hydroxymethyltransferase produces glycine

Question 2

How do we get mobilised amino acids to the liver for:
1. Nitrogen disposal
2. Glucose production from carbon
Ie how we get amino acids to get from here to liver?
Transports system.
One specific to muscle

Answer 2

Muscle:
Glucose alanine cycle➡ highly specific to muscle
-mobilising protein in muscle which releases amine group which will be transaminase onto alpha keto glutamate, but then that will transfer its amine group onto pyruvate which will give you alanine. Handy because In your muscle if there is any excess pyruvate in muscle during starvation, you have pyruvate dehydrogenase inhibited so you won’t be TCA cycle.
Meh lecture 09/04
Other transport system is assosiated with glutamine
-rely on converting amino acids and transferring there amine groups onto glutamate to form glutamine, which then flow through your blood, gets to your liver. Glutaminase cleaves of that amine group and feeds it into urea cycle.

This all serves 2 purposes:

• unloads nitrogen group into liver
• and bringing potential gouconeogenic carbon back to the liver where you can turn it back into glucose.

Question 3

Ammonia is toxic to CNS. Explain

Answer 3

NH3 (present as the ammonium ion (NH4) at physiological pH must be cleared from both the bloodstream and intra-cellularly to prevent neural toxicity. Alcoholics die of high level of amino that kills.

Question 4

How do we excrete AA nitrogen?

Answer 4

• want to utilise the carbon backbone, but have to dispose of nitrogen group through the urea cycle :)
• channeling amino acids to liver in form of glutamine
• glutaminase will release the amine group which will feed directly into urea cycle.
• another source is glutamate dehydrogenase, so glutamate that comes in can be broken down releasing another amine group
• the other one is aspartate transaminase, so any other aa floating in liver can unload their amine group onto oxaloacetate giving you aspartate which contributes the 2nd amine group, with the synthesis of urea and feeds back out into blood stream, pulled out through kidney and then piss it out.

Question 5

Only other way is activity of glutaminase in kidney.

Answer 5

-its picks up some glutamine and directly cleaves of amine groups and you directly excrete ammonia through urine.

Question 6

How do we handle N from other amino acids to convert them into:

1. Glutamate
2. Glutamine
3. Alanine
4. Aspartate

Answer 6

The other amino acids are all been converted into these forms, unloading their amine groups onto one of these 4 aa through the action of the key transaminases: 
Alanine transaminase 
Glutamate transaminase 
Aspartate transaminase 
Control: high Km

Question 7

Once you remove the amine group from the aa they form TCA cycle intermediates. Except for alanine, of you pull the Amine group of that you’ve got pyruvate. As a result?

Answer 7

Its all gouconeogenic carbon

Question 8

High protein diet

Answer 8

• high levels of protein coming in therefore aa pool grows
• high concentration of aa in that pool
• your transaminases and deamination pathways have a high Km, they swing into action.
• if you have high carb diet you props have relatively low carb in diet therefore a good portion of that carbon will be turned into glucose for brain etc
• once you have done that, all the excess carbon will turn into fat
• urea cycle enzymes increase in expression, have high Km. so when conc of N picks up urea cycle accelerates in activity

Question 9

Low protein diet

Answer 9

• low intake of protein therefore you have low concentration of aa
• therefore coz of high Km of your transaminases and deamination pathways you don’t deamination much aa at all and you can serve the aa that are available.
• protein synthesis has a high affinity for aa so low Km enzymes therefore protein synthesis can proceed.

Question 10

Summary: of each

Answer 10

Starvation:

• Lysosomal protein degredation
• Km transaminase/ deaminase
• induce urea cycle

High protein diet:

• Km transaminase/deaminase
• induce urea cycle

Low protein diet:

• Km transaminase/ deaminase
• induce urea cycle