Amino Acid Catabolism Flashcards
Where and how are proteins digested?
By pancreatic proteases (trypsin, chymotrypsin, exopepidases) in the small intestine
What type of transport mechanism do AA use?
Primarily through active Na+ dependent transport and through facilitated diffusion
Describe the Na+ active transport mechanism
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
What is a keto-acid?
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
What is the alpha-ketoacid paired with Ala?
Pyruvate
What is the alpha-ketoacid paired with Glu?
alpha-KG
What is the alpha-ketoacid paired with Asp?
OAA
What does Glutamate Dehydrogenase (GLDH) do?
Catalyzes the reversible rxn between alpha-KG and Glutamate (GLU) in the mitochondria
What allosterically activates GLDH?
ADP, NAD+, or Leucine
What allosterically inhibits GLDH?
GTP and NADH
What vitamin do transaminases require?
B6 (pyridoxyl phosphate)
What AA/alpha-ketoacid partner is required for transamination?
Glutamate/alpha-KG
How are AA oxidized in the liver and kidneys?
The amino group is converted to an alpha-keto acid and NH4+ is produced
How does the body generate and detoxify NH3?
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
Which AA are strictly Glucogenic? (there are 14)
Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Met, Pro, Ser, Thr, and Val
Which AA are strictly Ketogenic? (there are 2)
Leu and Lys
Which AA are both Glucogenic and Ketogenic? (there are 5)
Ile, Phe, Trp, Tyr, and Thr(?)
What AA can increase alpha-KG anapleurotically?
Pro, Gln, His, Arg, and Glu
Pro, Gln, His, and Arg can be converted to Glu
What AA can increase Succinyl CoA anapleurotically?
Thr, Met, Ile, and Val
They can all be converted into Propionyl CoA which can be converted to Succinyl CoA via B12 (Biotin)
What AA can increase Fumarate anapleurotically?
Tyr and Phe
What AA can increase Oxaloacetate anapleurotically?
Asn and Asp
Asn –> Asp –> OAA
What AA can increase Pyruvate anapleurotically?
Ala, Trp, Cys, Gly, Ser, and Thr
What AA can increase Acetyl CoA anapleurotically?
Leu, Ile, and Trp
What AA can increase Acetoacetyl CoA anapleurotically?
Leu, Lys, Phe, Trp, Tyr
What animals would you suspect Maple Syrup Urine Disease (MSUD) in?
Cattle (Herefords and polled Shorthorns)
Symptoms show up in 24 hrs, death in 5 days
What is MSUD?
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
What happens if there is a build up of alpha-Keto-beta-methylglutarate in the blood?
Blood pH goes down, the compound (alpha-keto-beta-methylglutarate) will spill over into urine, and the urine will smell like maple syrup
What happens if there is a build up of Isovalery CoA in the blood?
Urine will smell like sweaty feet
What happens if there is a build up of beta-Methylcrotonyl CoA?
Urine will smell like cat urine
What does the catabolism of Phenylalanine (Phe) normally produce?
Tyrosine (Tyr)
If there is a deficiency in phenylalanine hydroxylase (PAH) what occurs?
Phenylalanine (Phe) is transaminated to yield phenylpyruvate (a keto-acid), which is reduced to phenyllactate or decarboxylated to yield phenylacetate (mousy smelling urine)
What are the 3 main outcomes of Phenylketonuria (PKU)/hyperphenylalaninuria)?
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
If you lack Tyrosine, what symptoms would show up diagnostically?
Lacking pigment. To make melanin (required for pigment) you need Copper and Tyrosine. Animal tyrosinases typically require copper
Why are there no known diseases that are caused by deficiencies in Alanine, Glutamate, or Aspartate ?
Because they are non-essential AA
Can make Alanine from Pyruvate, Glutamate from alpha-KG, Aspartate from OAA
