Lecture 5 Flashcards
enzyme inhibitors
- endogenous inhibitors control mechanisms for biological systems (drugs and toxins)
irreversible inhibition
inhibitor is covalently linked to enzyme or bound so tightly dissociate from enzyme is very slow
reversible inhibition
- rapid binding equilibrium between enzyme and inhibitor
- enzyme activity fully restored when inhibitor is removed
what are the two types of reversible inhibitors?
competitive and nonceompetitive
examples of irreversible inhibitors
aspirin, nerve gas (DPF)
what groups are present on enzymes that can be inhibited by irreversible inhibitors?
seryl hydroxyl groups
what effect is there for the inhibition of COX2?
increases rates of heart attack
what part of aspirin is inhibited?
COX1 and COX2
Reversible competitive inhibitor
resembles the substrate and binds to active site
- completes with normal substrate
- diminishes rate of catalysis by reducing proportion of enzyme molecules that have bound substrate
what happens if DPF is inhibited?
leads to paralysis of the muscle
- causes respiratory failure
Reversible noncompetitive inhibitors
- binds to site on enzyme other than the active site
- alters the structure of the enzyme
enzyme still bind substrate in presence of inhibitor but is unable to catalyze reaction
how can competitive inhibition be used?
treating forms of intoxication: methanol (confused for alcohol) and ethylene glycol intoxication (antifreeze)
what organ metabolizes methanol?
liver and kidney
what are some effects of ethylene glycol?
depression of CNS, metabolic acidosis, renal damage, oxalate crystals
examples of noncompetitive inhibitors
enzymes with -SH (sulfhydryl) group (silver, lead, mercury), cleating agents
hydrolase
enzymes that catalyze hydrolytic cleavage reaction
proteases
degrade proteins by hydrolyzing bonds between amino acids
nucleases
degrade nucleic acids by hydrolyzing bonds between nucleotides
synthtases
synthesize molecules in anabolic reactions by joining two smaller molecules
isomerases
catalyze the rearrangement of bonds within a single molecule
polymerases
catalyze polymerization reactions in RNA and DNA synthesis
oxido-reductases
catalyze oxidation/reduction reactions (oxidase, reductases, dehydrogenases)
kinases
catalyzes transfer of a phosphate group from ATP to other molecules
phosphatases
catalyze the hydrolytic removal of phosphate groups from molecules
ATPases
catalyze the hydrolysis of ATP
what regulates enzyme activity?
concentration of enzyme and substrate, temperature, pH, coenzymes, prosthetic groups, cofactors, phosphorylation/dephosphorylation, zymogen activation
optimal pH for proteins
between pH 6 and pH 8 (human blood 7.4)
what pH does pepsin function at?
pH 2 –> it is a acidic gastric secretion
how does pH affect proteins?
- affects the charge
- affects binding of substrate to active site
- affects catalytic mechanism of enzyme itself
cofactor
- inorganic ions or low-molecular weight organic (nonprotein) or metalloorganic molecules
- bind through non-covalent interactions
how are prosthetic groups linked?
bound to enzymes by covalent linkages (tightly attached)
metal cofactors
- metal ions which can serve as electron pair acceptors
- form coordination bonds with enzymes that help properly position reactive groups during catalysis
what is phosphorylation?
addition of phosphate group to the side-chain hydroxyl groups of serine, theronine and tyrosine residues
how does phosphorylation affect enzyme activity?
depending on enzyme, phosphorylation can increase or decrease enzyme activity
what is a zymogen?
inactive precursor of enzymes
how are zymogens activated?
proteolytic cleavage of covalent bonds within precursor sequence
what enzymes are synthesized as zymogens?
digestive enzymes –> made in the stomach and pancreas
what enzyme produces trypsin?
trypsinogen –> cleavage by enzyme enteropeptidase
where is enteropeptidase located?
brush border of duodenal mucosa
pancreatic proteases are synthesized as inactive zymogens (T/F)
T
how does the pancreas protect itself from enzymes?
- zymogens packaged in lipid membrane bounded by secretory granules
- potent trypsin inhibitor, binds to active site of trypsin, blocking activity
acute pancreatitis
premature activation of the proteolytic and lipolytic enzymes of pancreas –> leads to destruction of pancreas
where are lysozymes found?
enzyme found in egg white, saliva, tears and other secretions
what does lysozyme do?
catalyzes the cutting of polysaccharide chains in cell walls of bacteria
what is creatine kinase associated with?
ATP regeneration in contractile or transport systems
what is the function of creatine kinase?
storage of high energy creatine phosphate in muscle
where is creatine kinase found?
skeletal muscle, heart muscle and brain
what are the three major forms of creatine kinase isoenzymes?
CK-BB (brain type –> brain and other tissue)
CK-MM (muscle type –> heart and skeletal muscle
CK-MB (hybrid type–> heart and small amount in skeletal muscle)
what diseases are associated with high creatine kinase levels?
acute myocardial infarction (AMI), muscular dystrophy, hypothyroidism
what disease does elevated serum CK-MM indicate?
skeletal or cardiac muscle injury –> strenuous physical activity or intramuscular injections
what disease does elevated serum CK-BB indicate?
damage to CNS, tumors, childbirth
which creatine kinase isoenzyme is the major form in serum?
CK-MM: makes up 94-100%
