BioChem Enzyme Regulation (11)
Home > Flashcards > Print Preview
The flashcards below were created by user
on FreezingBlue Flashcards
. What would you like to do?
alanine transaminase (ALT)
- presence of this enzyme in the blood stream is indicative of liver damage
- (catalyses the interconversion of alanine and pyruvate)
- LOW serum levels of alpha-1 antitrypsin is indicative of liver damage
- (normally secreted by liver)
What can elevated enzyme activity in blood plasma indicate?
What is a zymogen?
An inactive enzyme precursor
What is the basic concept behind zymogens?
an enzyme's active site is blocked or its residues are out of alignment until a proteolytic cleavage at a specific activation site on the chain
How are zymogens activated?
By rapid proteolytic cleavage
abundant conversion enzyme in the blood coagulation cascade
performs two proteolytic cleavages which turn prothrombin into its active form, thrombin
components of the prothrombin-converting complex: (4)
- 1) calcium
- 2) phospholipids
- 3) Factor V
- 4) Factor X
- (3 & 4 are blood coagulation proteins)
What do Factor V and Factor X do to thrombin?
Factor V cleaves prothrombin to prethrombin. Factor X cleaves prethrombin to thrombin.
formed after a single proteolytic cleavage by prothrombin-converting complex; a second cleavage between residues 15 and 16 by the same complex gives thrombin
What happens to prethrombin after cleavage between residues 15 and 16 to form thrombin?
- light chain residues = 1-15 don't change much; they're held to the rest of the enzyme (heavy chain) by a disulfide bond
- in the active enzyme, residue 16 reaches over the enzyme and forms a stabilizing interaction with residue 194
- this repositioning results in the proper formation of the catalytic triad, containing the active serene protease nucleophile residue, serine 195
the activation of thrombin is:
Where in the cell is the mature form of thrombin synthesized?
on the cell membrane surface but it's water soluble
What class of enzymes is involved in activating prothrombin and fibrinogen in the blood clotting cascade?
Prothrombin is modified by gamma-carboxylation of which amino acid residues at its N-terminus?
Which enzyme catalyzes the conversion of soluble fibrinogen to insoluble fibrin?
Why is it important for prothrombin to be gamma-carboxylated?
It allows for calcium binding, which is required to anchor prothrombin to the cell membrane
Does gamma-carboxylation of thrombin regulate enzyme activity?
gamma-carboxylation is a post-translational modification that DOES NOT directly regulate enzyme activity, but IS required for formation of the active enzyme for blood coagulation
a cofactor required for the gamma-carboxylation of prothrombin
- a vitamin K analogue that is used to treat thrombosis (too much blood clotting)
- Vitamin K ANALOGUES interfere with the carboxylation reaction
How does Warfarin work?
It inhibits the gamma-carboxylation reaction of prothrombin, thereby reducing the number of prothrombin molecules attached to the cell membrane. This reduces the amount of active thrombin that can be synthesized by a cell.
Carboxyglutamate in prothrombin mediates the process of attaching itself to blood vessel endothelium by binding to:
an anti-coagulant that promotes the high-affinity binding of antithrombin to thrombin, thereby reducing blood clotting
How is thrombin INactivated?
thrombin is inactivated when the protein antithrombin binds to its active site
- a type of serine protease that breaks down elastin fibers; released by neutrophils into lung tissue
- unregulated elastase activity would result in emphysema
What is the role of alpha1-antitrypsin in the lungs?
- it's an irreversible elastase inhibitor that prevents neutrophil-produced elastase from degrading elastin fibers in the lungs
- individuals with mutated alpha1-antitrypsin often have lung destruction and emphysema
How does cigarette smoking affect the activity of alpha1-antitrypsin?
- Cigarette smoke oxidizes a methionine residue on alpha1-antitrypsin involved in binding elastase
- methionine --> methionine sulfoxide
- Oxidation of this residue PREVENTS inhibition of elastase, results in over-degradation of lung elastin fibers --> lung scarring & emphysema
How can oxidation of alpha1-antitrypsin as a result of smoking be treated?
intravenous administration of alpha1-antitrypsin; protein diffuses from blood into lung, where it reaches therapeutic levels in the fluid surrounding epithelial cells
phosphorylation or dephosphorylation modifies the ______ of an amino acid residue
charge; if said amino acid residue (serine, threonine, or tyrosine) is in or near the active site of an enzyme, the enzyme activity MAY be changed
Which amino acids can typically be modified by enzymatic phosphorylation/dephosphorylation?
serine, threonine and tyrosine
How does phosphorylation of a kinase alter it's catalytic abilities?
phosphorylation, specifically in the activation loop of a kinase, leads to a 1000 fold increase in catalytic activity (eg. increases substrate binding)
- reversibly compete with a substrate for an enzyme's active site
- usually resemble the substrate in structure
- they are able to fit into the active site but cannot be acted upon by the enzyme
- eg. ethanol is a competitive inhibitor of ethylene glycol
- (binding site only)
competitive inhibition; Vmax reached eventually but it takes much more substrate than usual
with competitive inhibitors:
the more you use, the more COMPETITION there is with substrate
- Ki measures the affinity of an enzyme for a certain inhibitor
- the SMALLER the Ki, the GREATER the inhibitor's effectiveness
What is the effect of competitive inhibitors on Km and Vmax?
Competitive inhibitors increase Km but DO NOT alter Vmax
Km measures the affinity of an enzyme for its substrate. The smaller the Km, the greater the enzyme's affinity for its substrate. Km is also defined as 1/2 Vmax.
- bind to the enzyme in a location OTHER THAN the active site (whether or not a substrate is present) & affect the amino acid residues of the enzyme involved in the catalysis of the reaction
- (catalytic machinery only)
noncompetitive inhibition; Vmax never achieved
What is the effect of noncompetitive inhibitors on Km and Vmax?
Noncompetitive inhibitors LOWER Vmax but do NOT alter Km
using noncompetitive inhibitors, Vmax:
CANNOT be reached, no matter how much substrate is added
- form very tight complexes, kill the enzyme by forming covalent bonds with it
- eg. DIFP
an irreversibly inhibitor that inhibits serene proteases, specifically the enzymatic hydrolysis of acetylcholine (NT) by acetylcholine esterase, thus acting as an effective nerve gas
recovery from reversible inhibitors:
related to half-life (hours)
recovery from irreversible inhibitors:
the effective time relevant for recovery from irreversible inhibitors is the time required for re-synthesis of an enzyme
What are enzyme activators?
positive effectors that promote an enzyme to exist in its active form where it is a more effective catalyst
True or False: allosteric enzymes often catalyze the first step of a reaction sequence?
What does an allosteric enzyme curve look like?
What is meant by the term 'feedback inhibition'?
Feedback inhibition is a phenomenon by which the end product of a reaction or sequence of reactions inhibits the enzyme or enzymatic cascade. When sufficient product is produced, the system automatically turns itself off.
Phosphofructosekinase 1 (PFK1)
- enzyme responsible for phosphorylating fructose-6-phosphate (using ATP) in the committed step of glycolysis
- -is allosterically activated by AMP (signals that cell is energy poor)
- -is reversibly inhibited by ATP (product of glycolysis)
List three common characteristics of committed steps:
- 1. They are functionally irreversible
- 2. They occur early in the enzymatic pathway
- 3. They occur in only one pathway
Name an inhibitor of the enzyme aspartate transcarbamoylase (ATCase)
Cytidine triphosphate (CTP)
Name an activator of the enzyme aspartate transcarbamoylase (ATCase)
Adenosine triphosphate (ATP)
What would you like to do?
Home > Flashcards > Print Preview