Amino Acid Metabolism

Question 1

Amino Acids

Answer 1

20 amino acids (9 essential- diet, 11 non-essential- synthesized by body)

Contains an amino group, carboxyl group, and a side chain

Question 2

Amino Acid ingestion

Answer 2

Protein is ingested and broken down into amino acids that enter the serum. Eventually almost all of the amino acids end up in the liver’s amino acid pool.

All amino acids except
- Brain chain amino acids (skeletal muscle)
- Glutamine (intestine, kidney)
- Valine (brain)

Question 3

3 routes for amino acids

Answer 3

1. Used to form tissue protein
2. Formation of non-protein cellular molecules
3. Formation of alpha-keto acids (intermediates for TCA)

Excess amino acids cannot be stored

Question 4

alpha-keto acid formation (Transamination)

Answer 4

Amino acids + alpha-ketoglutarate forms glutamate + alpha-keto acids

Uses transaminase enzymes

Question 5

Transaminase enzymes

Answer 5

• Alanine aminotransferase (ALT) : alanine to pyruvate
• Aspartate aminotransferase (AST): aspartate to oxaloacetate

Question 6

Clinical relevance of ALT and AST

Answer 6

Both ALT and AST are enzymes that are typicall found in the tissue. If found in the blood, it indicates that there is tissue damage allowing for their release.

Question 7

high ALT in blood

Answer 7

Found in kidney, heart, muscle, liver.

High levels indicate liver damage in cats and dogs. Not used in large animals

Question 8

High AST in blood

Answer 8

Found in liver, RBC, heart, skeletal muscle

High levels indicate possible muscle trauma (rhabdomyolysis) or liver disease

Question 9

Fate of glutamate

Answer 9

The universal end product of transamination.

Glutamate is deaminated to recycle alpha-ketoglutarate. The NH4+ enters the urea cycle to remove the nitrogenous toxic waste

Question 10

Fate of Alpha- keto acids (Glucogenic vs. ketogenic)

Answer 10

alpha-keto acids are used for ketone synthesis or TCA/ETC

Glucogenic amino acids: amino acids that form alpha-keto acids that go directly into the TCA cycle

Ketogenic amino acids: amino acids that form acetyl-CoA and need another molecule such as oxaloacetate to enter the TCA cycle OR amino acids used to synthesize ketone bodies

Question 11

Non-protein derivatives

Answer 11

Tyrosine derivative

Glutamate derivatives

Question 12

Tyrosine derivatives

Answer 12

• Catecholamines: amine containing catechol. Includes Dopamine, Norepinephrine, Epinephrine. Act as neurotransmitters and hormones
• Thyroid hormones (Tetraiodothyronine T4, Triiodothyronine T3). Made of tyrosine and iodine. Every cell requires them to regulate metabolism.

Question 13

Glutamate derivatives

Answer 13

GABA (gamma-aminobutyric acid)
A major inhibitory neurotransmitter in the CNS. GABA released at presynaptic neuron. Binds at postsynaptic neuron causing Cl- to enter and inhibits nerve impulse. Sedatives will enhance GABA effects

Glutamate
Excitatory neurotransmitter. Brings Na+ into neuron.

Question 14

GABA clinical relevance

Answer 14

Excess glutamate (excitatory) or inadequate GABA (inhibitory) will result in over-excitation and display as epilepsy.

Question 15

GABA agonists

Answer 15

Phenobarbitol or Benzodiazepine

Binds to receptors bringing Cl- into neuron, inhibitory

Question 16

Ivermectine

Answer 16

Used in parasite control. Triggers paralysis in parasites by enhancing inhibitory neurotransmission.

GABA neurons are in CNS of mammals but PNS in arthropods and nematodes. It has low toxicity in mammals because they have MDR1 drug pump that removes drug preventing it crossing the BBB.

Question 17

Ivermectin sensitivity

Answer 17

Some dogs have mutations in the MDR1 pump. Most likely in collies. Even if sensitive, would need a high dose to see symptoms.

Clinical signs: ataxia, depression