Amino Acid Catabolism

Question 1

Where and how are proteins digested?

Answer 1

By pancreatic proteases (trypsin, chymotrypsin, exopepidases) in the small intestine

Question 2

What type of transport mechanism do AA use?

Answer 2

Primarily through active Na+ dependent transport and through facilitated diffusion

Question 3

Describe the Na+ active transport mechanism

Answer 3

AA and Na+ are brought into the intestinal cell through the luminal/apical membrane by a cotransporter. The AA diffuses into portal circulation at the basal membrane. Na+ accumulates in the cell, 3 Na+ pumped out in exchange for 2 K+ in, requiring ATP

Question 4

What is a keto-acid?

Answer 4

Organic acid containing a ketone and carboxyl acid; a ketone is a carbonyl (C=O) between 2 other C. It is an alpha-keto-acid when the keto group is on the C adjacent to the carbonyl

Question 5

What is the alpha-ketoacid paired with Ala?

Answer 5

Pyruvate

Question 6

What is the alpha-ketoacid paired with Glu?

Answer 6

alpha-KG

Question 7

What is the alpha-ketoacid paired with Asp?

Answer 7

OAA

Question 8

What does Glutamate Dehydrogenase (GLDH) do?

Answer 8

Catalyzes the reversible rxn between alpha-KG and Glutamate (GLU) in the mitochondria

Question 9

What allosterically activates GLDH?

Answer 9

ADP, NAD+, or Leucine

Question 10

What allosterically inhibits GLDH?

Answer 10

GTP and NADH

Question 11

What vitamin do transaminases require?

Answer 11

B6 (pyridoxyl phosphate)

Question 12

What AA/alpha-ketoacid partner is required for transamination?

Answer 12

Glutamate/alpha-KG

Question 13

How are AA oxidized in the liver and kidneys?

Answer 13

The amino group is converted to an alpha-keto acid and NH4+ is produced

Question 14

How does the body generate and detoxify NH3?

Answer 14

Glutamate + NH4 + ATP --> Glutamine
-using Glutamine synthetase
-done in brain and other tissues
-Glutamine is transported in bloodstream and picked up by liver and kidneys to convert Glutamine back to Glutamate and Urea using Glutaminase/asparaginase:
Glutamine + H2O --> Glutamate + NH3

Question 15

Which AA are strictly Glucogenic? (there are 14)

Answer 15

Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Met, Pro, Ser, Thr, and Val

Question 16

Which AA are strictly Ketogenic? (there are 2)

Answer 16

Leu and Lys

Question 17

Which AA are both Glucogenic and Ketogenic? (there are 5)

Answer 17

Ile, Phe, Trp, Tyr, and Thr(?)

Question 18

What AA can increase alpha-KG anapleurotically?

Answer 18

Pro, Gln, His, Arg, and Glu

Pro, Gln, His, and Arg can be converted to Glu

Question 19

What AA can increase Succinyl CoA anapleurotically?

Answer 19

Thr, Met, Ile, and Val

They can all be converted into Propionyl CoA which can be converted to Succinyl CoA via B12 (Biotin)

Question 20

What AA can increase Fumarate anapleurotically?

Answer 20

Tyr and Phe

Question 21

What AA can increase Oxaloacetate anapleurotically?

Answer 21

Asn and Asp

Asn –> Asp –> OAA

Question 22

What AA can increase Pyruvate anapleurotically?

Answer 22

Ala, Trp, Cys, Gly, Ser, and Thr

Question 23

What AA can increase Acetyl CoA anapleurotically?

Answer 23

Leu, Ile, and Trp

Question 24

What AA can increase Acetoacetyl CoA anapleurotically?

Answer 24

Leu, Lys, Phe, Trp, Tyr

Question 25

What animals would you suspect Maple Syrup Urine Disease (MSUD) in?

Answer 25

Cattle (Herefords and polled Shorthorns)

Symptoms show up in 24 hrs, death in 5 days

Question 26

What is MSUD?

Answer 26

A defect in catabolism of branch chain amino acids: Leu, Ile, and, Val
One common transaminase enzyme impacts all 3 AA. The problem is the build up of all 3 AA, not just the one that smells

Question 27

What happens if there is a build up of alpha-Keto-beta-methylglutarate in the blood?

Answer 27

Blood pH goes down, the compound (alpha-keto-beta-methylglutarate) will spill over into urine, and the urine will smell like maple syrup

Question 28

What happens if there is a build up of Isovalery CoA in the blood?

Answer 28

Urine will smell like sweaty feet

Question 29

What happens if there is a build up of beta-Methylcrotonyl CoA?

Answer 29

Urine will smell like cat urine

Question 30

What does the catabolism of Phenylalanine (Phe) normally produce?

Answer 30

Tyrosine (Tyr)

Question 31

If there is a deficiency in phenylalanine hydroxylase (PAH) what occurs?

Answer 31

Phenylalanine (Phe) is transaminated to yield phenylpyruvate (a keto-acid), which is reduced to phenyllactate or decarboxylated to yield phenylacetate (mousy smelling urine)

Question 32

What are the 3 main outcomes of Phenylketonuria (PKU)/hyperphenylalaninuria)?

Answer 32

1 - Phenylketoacid accumulates and have phenylketoacidosis
2 - Phenylacetate causes mousy smelling sweat and urine
3 - A defect in PAH means that tyrosine becomes essential in the diet

Question 33

If you lack Tyrosine, what symptoms would show up diagnostically?

Answer 33

Lacking pigment. To make melanin (required for pigment) you need Copper and Tyrosine. Animal tyrosinases typically require copper

Question 34

Why are there no known diseases that are caused by deficiencies in Alanine, Glutamate, or Aspartate ?

Answer 34

Because they are non-essential AA

Can make Alanine from Pyruvate, Glutamate from alpha-KG, Aspartate from OAA