Proteins Flashcards
What are the two modified amino acids in collagen?
hydroxyproline
hydroxylysine
What is required for Hydroxyproline and Hydroxylysine synthesis?
Vitamin C is a required cofactor for their enzymatic generation
Which are the two ketogenic amino acids
lysine
leucine
Which are the four aa that can be keto or gluco
isoleucine
tryptophan
tyrosine
phenylalanine
Which aa strengthen collagen?
Hyp
Hyl
How does Hyp and Hyl strenghten collagen?
Interstrand covalent crosslinks between Hyl and Lys
Hyp - interstrand Hydrogen bonding
Prolyl hydroxylase
Lysyl hydroxylase
convert Proline to Hyp
convert Lysine to Hyl
respectively
Both enzymes require vitamin C
Consequence of VitC deficiency?
Scurvy - reduced strength of collagen fibrils
Gamma Carboxyglutamate?
modified form of glutamate - carboxylated
Important in prothrombin membrane targeting
Gamma glutamyl carboxylase
TM protein that carboxylates glutamate to form Gla
- vitamin K dependent!!!
How does carboxylating glutamate influence protein?
enables chelation of Ca2+ –> conformational changes
Prothrombin uses____ to target membrantes?
Gla
Gamma carboxyglutamate
2 ways to degrade protein
Proteosomal targeting - via ubiquitination (ATP dependent)
Lysosomal degradation (ATP independent)
Which AA is ubiquitinated?
it appears lysine
proteolytic degradation of proteins in stomach
via pepsin - only N terminal side of aromatic aa
proteolytic degradation of proteins in intestine?
trypsin (activated by enteropeptidase)
chymotrypsin (activated by trypsin)
(both serine proteases)
carboxypeptidase A and B
(both metalloproteases activated by enteropeptidase)
aminotransferase
transfer amino groups
aminotransferase Keq
near 1 (so reversible and mainly directed by concentration of substrate and product)
what is the major goal of transamination?
produce Aspartate and NH3 for the urea cycle
where are aminotransferases located?
mainly in the cytosol of liver, kidney, intestine, and muscle cells
What do increased levels of aminotransferases tell us?
LIVER DAMAGE/DISEASE
Especially
alanine aminotransferase
aspartate aminotransferase
Transamination feeds?
the urea cycle with aspartate (AST) and ammonia (via Glu dehydrogenase of glutamate post ALT)
Aminotransferases require what con-enzyme?
PLP (derivative of vitamin B6) - hold amino-group by forming schiff base with aminotransferase
What are the 4 control point for protein catabolism
1) Directionality of transamination (by ALT and AST)
2) N-acetylglutamate
3) Directionality of Glu dehydrogenase
4) ATP and GTP inhibit Glu Dehydrogensase — ADP and GDP activate
Why is it important to get rid of ammonia via urea?
hyperammonemia is toxic - cerebral edema / coma / death
NET UREA
3ATP + HCO3- + NH4+ +Aspartate –> 2ADP + AMP + 2Pi + PPi + fumerate + urea
Two sources of nitrogen in urea cycle?
NH4+ and aspartate
