Amino Acid Degradation/Urea Cycle Flashcards
What is secreted by parietal cells in the stomach?
HCl
What is secreted by chief cells in the stomach?
Pepsinogen
What class of enzyme is pepsinogen?
zymogen
What is the active form of pepsinogen?
pepsin
What changes pepsinogen into its active form pepsin?
low pH
What does pepsin do?
Acts as an endopeptidase, cleaving peptide bonds to form smaller peptides and some free aa
What side group does pepsin prefer?
CO group provided by an aromatic or acidic amino acid
Where are pancreatic zymogens activated??
small intestine
What cellular mechanism absorbs amino acids?
Na+ transport proteins
What disease is characterized by an inability to absorb amino acids in the kidney due to defective Na+ amino acid pumps?
Hartnup disease
Why do patients with hartnup disease often show symptoms of pellagra?
Because they can’t absorb normal amounts of tryptophan, which is a precursor for niacin synthesis.
Patients with Cystinuria have problems absorbing which amino acid?
Cystine
What molecule tags proteins for degradation intracellularly?
ubiquitin
What protein degrades proteins inside the cell tagged by ubiquitin?
26S proteasome
Besides in the cytosol with proteasomes, where can proteins be degraded in the cell?
lysosomes
What type of enzymes degrade proteins in lysosomes and what is their optimal pH?
acid hydrolases
pH 5
What are two examples of enzymes that degrade proteins extracellularly?
Serine proteases matrix metalloproteases (Ex collagenases)
Where does the urea cycle take place?
Liver
What is the only organ with all of the enzymes for urea synthesis?
Liver
Which is very toxic to the CNS, ammonia or ammonium ion?
ammonia (in equilibrium with ammonium ion)
What are the two nontoxic compounds that ammonia is converted to?
Urea and glutamine
What are the two types of reactions used to remove the amino groups in amino acid catabolism?
Transamination and deamination
What type of reaction moves amino groups into glutamate?
Transamination
What type of reaction directly releases ammonium ions?
Deamination
What type of enzymes catalyze the transfer of an alpha-amino group from an amino acid to an alpha-ketoacid during transamination?
Aminotransferases (transaminases)
Serum levels of what two amino acid transferases are used to evaluate liver damage?
Aspartate aminotransferase (AST) Alanine aminotransferase (ALT)
What cofactor is required for aminotransferase reactions?
pyridoxal phosphate (PLP)
What vitamin is PLP derived from?
B6
Are transamination reactions reversible?
Yes
What are the three types of deamination reactions?
Oxidative Deamination
Hydrolytic Deamination
Nonoxidative deamination
Which deamination reaction is PLP dependent?
nonoxidative deamination
Oxidative deamination is a reaction in liver mitochondria and is catalyzed by what enzyme?
glutamate dehydrogenase
What two side aa side chain groups are targeted by hydrolytic deamination?
glutamine and asparagine
What is an important deamination reaction in the kidney?
hydrolytic damination of glutamine by glutaminase
What two amino acid side chains undergo nonoxidative damination?
Serine
Threonine
What are the enzymes of the two major nonoxidative damination reactions?
serine dehydratase
threonine dehydratase
both use PLP prosthetic group
What molecules transport most nitrogen from other tissues to liver or kidney?
Alanine
Glutamine
Glutamine synthetase is one of three human enzymes that can fix ____ in a carbon compound
NH4+
Why do mutations in glutamine synthetase cause severe brain malformation is newborns?
Glutamate is a neural toxin, large amounts of it accumulate in the brain
What conditions would produce a postive-nitrogen balance in a patient? Need to increase protein synthesis
Physical trauma
Growing child
excreted N < consumed N
What conditions would produce a negative-nitrogen balance in a patient? Body protein degraded to synthesis essential proteins
protein malnutrition or starvation
excreted N > consumed N
What is the expectation of most all urea cycle defects?
hyperammonemia
There is no other way to get rid of NH4+
What enzyme is involved in the rate limiting step of the urea cycle?
Carbamoyl phosphate synthetase 1 (CPS 1)
Where is CPS1 located?
mitochondria
What does CPS require as a cofactor?
N-acetylglutamate (NAG)
allosteric activator
Where is NAG synthesized?
Mitochondria by N-acetylglutamate synthase
NAG synthase is positively regulated by the presence of?
Argenine
Which form of CPS 1 is active? the dimer or the monomer?
monomer
What does CPS1 reaction require?
2 ATP
NH3 from deamination rxns
What molecule is the first and last step of urea synthesis?
Ornithine
