NBME - 6/11 - Inter-Tissue Relationships in AA metabolism

Question 1

As discussed before, some proteins in a fasted state just hang tight in the muscle to get degraded.

Branched chain amino acids do this, and the ones we need to focus on are Valine and Isoleucine. Describe their breakdown in the muscle.

Answer 1

Valine and isoleucine produce succinyl-CoA via the mechanism described in the previous deck.

Succinyl CoA feeds into the TCA cycle and forms malate, generating energy.

Malate can be converted by the malic enzyme to pyruvate.

Question 2

Let’s talk about amino acid metabolism in the kidney, which we have not yet.

The kidney takes up _____ which is deaminated by _____ forming ____ and ______ which is converted to _____ and _____.

Answer 2

The kidney takes up glutamine which is deaminated by glutaminase forming ammonia and glutamate which is converted to alanine and serine.

Question 3

Where does Ammonia go once it is generated in the kidney and what does it do?

Answer 3

It gets released into the urine, where it forms NH4+, buffering the hydrogen ions produced by phosphoric acid, sulfuric acid (produced from cysteine) and various metabolic acids.

Question 4

We discussed that the glutamate formed in the kidney is turned to Alanine and Serine. How?

Answer 4

Glutamate is transaminated to alpha ketoglutarate, which enters the TCA cycle and is converted to malate. Malate is oxidized to oxaloacetate which is turned by PEP Carboxylase to PEP.

PEP feeds into glycolysis and makes Alanine and Serine.

Alanine and Serine get dumped into the blood, unlike Ammonia which got dumped into the urine.

So in summary: Glutamate to alpha to malate to oxalo to PEP to Alanine/Serine

Question 5

Describe Amino Acid metabolism in the liver

Answer 5

The liver takes up Alanine, serine, and other amino acids from the blood and converts their nitrogen to urea and their carbons to glucose or to ketone bodies, which are released into the blood and oxidized by other tissues.

Question 6

Where is Glutamine used most in the body?

Answer 6

Gut and kidneys. Makes Alanine which the liver loves.

Question 7

Why do we not transport Glutamate as is?

Answer 7

Glutamate is an excitatory Neurotransmitter, we need to change it for shipping.

Question 8

Skeletal muscle responds to what hormones?

Answer 8

Skeletal muscle only responds to insulin (no glucagon). Glucagon can only convince two tissues to have its receptors: Adipose and liver. However, Muscle does respond to Epinephrine, which does the job in a similar manner

Question 9

Symptoms of Ammonia Toxicity

Answer 9

Seizures, somnolence, apnea that all lead to coma.

We can also see cerebral edema.

Question 10

How does Ammonia Toxicity cause neuro issues?

Answer 10

1. Excess NH3 shifts the Glu/Gln balance towards Gln, leading to a loss of Glu, a key NT and intermediate of the TCA cycle.
2. Gln enters the mitochondria of astrocytes, hydrolyzing glutamate to NH3, which increases formation of ROS and opens up a mitochondrial transition permeability pore.
3. NH3 can also increase cell permeability to Ca

Question 11

Glucocorticoids on Fuel metabolism

Answer 11

Encourages:

• Gluconeogenesis
• Glycogen storage
• Muscle breakdown for amino acids
• TG to glycerol and FA from adipose tissue

Basically you are preparing the body for epinephrine, which will tell glucose to be released throughout the body.

Question 12

Hypercatabolic state

Answer 12

Excessive metabolic breakdown of a specific substance or of body tissue in general, leading to weight loss and wasting.

Question 13

Times where we will have an expected negative-nitrogen balance:

Answer 13

in trauma, sepsis, post-surgery