FORM & FUNCTION (AA Metabolism)

Question 1

Protein structure:

Answer 1

-primary structure: AA residues
-secondary structure (alpha-helix, beta-sheet)
-tertiary structure (polypeptide chain)
-quaternary structure (assembled subunits, dictates the function)
*digestion or muscle breakdown (starvation)
*protein contributes to 10-15% of energy

Question 2

Amino acids:

Answer 2

-20 AA
>9 essential (dietary only)
>11 non-essential (synthesized by body)
-can be both an acid or base depending on the R group

Question 3

Components of an AA:

Answer 3

-side chain
-amino group
-carboxyl group (proton donor)

Question 4

AA catabolism:

Answer 4

1. Ingested protein (stomach)
2. Polypeptides (small intestine)
3. Amino acids (small intestine)
4. Amino acids (serum – most goes to the liver)

Question 5

AA catabolism location:

Answer 5

-liver governs distribution of AA (like an airport)
-most AA are catabolized in the liver except:
>BCAA (skeletal muscles)
>Gln (intestine, kidney)
>Val (brain)

Question 6

AA pool:

Answer 6

1. Building blocks to synthesize new tissue proteins
2. Forming non-protein cellular molecules (ex. NTs)
3. Generates intermediates to feed into other energy pathways (via alpha-keto acids)
   *excess AA cannot be stored
   *will likely end up as fat molecules

Question 7

Goal of excess AA breakdown:

Answer 7

-to form alpha-keto acids (energy precursors)
>gluconeogenesis
>lipogenesis
>ketogenesis

Question 8

Alpha-keto acids:

Answer 8

-requires the removal of alpha-amino group (1st step of catabolism)
>alpha-ketoglutarate acts as an acceptor of the alpha-amino group
*transamination

Question 9

Transamination:

Answer 9

-alpha-ketoglutarate accepts an alpha-amino group
-catalyzes by transaminases (aminotransferase)
-some require additional enzymes, but all end products are alpha-keto acids that form an energy metabolite
*get glutamate

Question 10

Clinical relevance: aminotransferase:

Answer 10

-serum activity of aminotransferase used as an indicator of tissue damage
-enzyme is normally inside the tissue
*release into serum indicates tissue damage
Ex. ALT and AST

Question 11

Alanine transaminase (ALT):

Answer 11

-alanine to pyruvate
-found in kidney, heart, muscle and liver (very high)
-high levels (>2-3 fold increase) indicate liver damage in cats and dogs
*not used in large animals (low ALT activity in liver)

Question 12

Aspartate transaminase (AST):

Answer 12

-aspartate to oxaloacetate
-found in liver, RBC, heart, skeletal muscle (highest conc.)
-high levels indicate possible muscle trauma (rhabdomyolysis) OR liver disease

Question 13

Fate of Glutamate:

Answer 13

-universal end product of transamination
-processed in the liver
-De/transaminated to recycle alpha-ketoglutarate
-NH4+ enters the urea cycle

Question 14

NH+ enters the urea cycle:

Answer 14

-important step to remove toxic nitrogenous waste (renal section)
*nitrogen are toxic in high amounts

Question 15

AA acid substrates for CAC:

Answer 15

-acetyl-CoA is NOT glucogenic
>1 oxaloacetate is required to form citrate
*this mechanism is critical for starvation survival

Question 16

Glucogenic AA:

Answer 16

-form oxaloacetate to enter gluconeogenesis

Question 17

Ketogenic AA:

Answer 17

-form acetyl-CoA or acetoacetyl-CoA

Question 18

Non protein derivatives:

Answer 18

-tyrosine derivatives
-glutamate derivatives

Question 19

Tyrosine derivatives:

Answer 19

-catecholamines
-Thyroid hormones

Question 20

Catecholamines:

Answer 20

-amine containing catechol (neurotransmitter & hormone)
Ex. dopamine, E and NE

Question 21

Dopamine:

Answer 21

-NT
-regulates motor movement

Question 22

NE and E:

Answer 22

-NT and hormone
-produced by adrenal cortex
-regulates flight-or-flight response
-acts on alpha and beta receptors to stimulate CNS

Question 23

Thyroid hormones examples:

Answer 23

-tetraiodothyronine (T4)
-triiodothyronine (T3)

Question 24

Thyroid hormones:

Answer 24

-2x tyrosine + iodine molecules
-iodine from diet (iodized salt, seafood, dairy)
-every cell requires thyroid hormones to regulate metabolism
*hypothyroidism (endocrine disease) linked to obesity

Question 25

Glutamate derivatives:

Answer 25

-glutamate is a universal produced when alpha-ketoglutarate is broken down
-GABA: gamma-aminobutyric acid
*major inhibitory NT in the CNS
>reduces neuronal excitability/block nerve impulses

Question 26

GABA as NT:

Answer 26

1. Released from presynaptic neuron
2. Binds to postsynaptic neuron
3. Cl- enters postsynaptic neuron
   -negative charge causes inhibitory post synaptic potential=*inhibits nerve impulse
   >hyperpolarisation

Question 27

Sedatives:

Answer 27

-enhance GABA effects
Examples:
-benzodiazepine
-zolpidem (Ambien)

Question 28

Glutamate as NT:

Answer 28

-serves as an excitatory NT
1. Released from presynaptic neuron
2. Binds to postsynaptic neuron
3. Na+ enters postsynaptic neuron
-positive charge causes excitatory post synaptic potential
>depolarisation

Question 29

GABA Clinical Relevance: Epilepsy

Answer 29

-epilepsy: over stimulation/excitation
-excess glutamate (depolarization) or inadequate GABA (hyperpolarization)
-over-excitation of neuronal activity

Question 30

Therapeutic: GABA agonists:

Answer 30

-phenobarbital
-benzodiazepine

Question 31

Ivermectine: (GABA related drugs)

Answer 31

-in parasite control
-broad spectrum: heartworm, lice, scabies (nematodes and arthropod)
-triggers paralysis in parasites (enhance inhibitory NT)
-low toxicity in mammals
*in mammals, removed by a drug pump called MDR1, does not cross BBB

Question 32

GABA neurons (ivermectine):

Answer 32

-mammals: located in CNS
-arthropods & nematodes: PNS

Question 33

MDR1:

Answer 33

-multiple drug resistance 1

Question 34

Ivermectin sensitivity: clinical signs

Answer 34

-most commonly ataxia or depression
-cattle: 20-40x the therapeutic dose (TD)
-horses: 10x TD
-pigs: 100x TD
-dogs! Collies: 15-30x the therapeutic dose
>beagles: greater than 200x TD

Question 35

Collies:

Answer 35

-70% frequency have the MDR1 mutation