Enzymes Part 3 Flashcards
- importance of cofactors & prosthetic groups - enzyme activation - apoptosis - regulatory mechanisms of enzyme activity
The catalytic activity of many enzymes depends on the presence of small molecules called:
cofactors or coenzymes
coenzymes
- small non-protein molecules
- helpers
cofactors are subdivided into 2 groups
- metals
2. small organic molecules (coenzymes)
small organic molecules
coenzymes
cofactor
activate inactive form of enzymes to convert into active forms
apoenzyme
inactive form of enzyme
holoenzyme
active form of enzyme after being bound by coenzyme
prosthetic group
tightly bound coenzymes
- e.g. heme group
co-substrates
loosely associated coenzymes
coenzyme
- small organic molecule
- often derived from vitamins
- can be tightly or loosely bound to an enzyme
- tightly associated with enzyme’s active site + assists with catalytic function
Biotin
- forms transient covalent bond to COO- group
- can’t be synthesized by humans; must be supplied by diet (vitamin)
zymogen
- inactive precursor
- aka proenzyme
- biochemical change usually occurs in Golgi bodies
proteolytic activation
- specific part of enzyme is cleaved in order to activate it
- cleavage does not require energy (ATP)
- occurs just once in the life of an enzyme molecule
proteolysis
- digestive enzymes that hydrolyze proteins are synthesized as zymogens in stomach and pancreas
pancreas
- secretes zymogens partly to present enzymes from digesting proteins in the cells in which they are synthesized
- enzymes like pepsin and trypsin are created in the form of pepsinogen and trypsinogen (inactive zymogens)
pepsinogen
- activated when chief cells release it into gastric acid -> hydrochloric acid partially activates it
- another partially activated pepsinogen completes activation by removing peptide, turning pepsinogen into pepsin
accidental activation of zymogens
- occur when secretion duct in pancreas in blocked by gallstone resulting in acute pancreatitis
protein hormones synthesized as inactive precursors
- e.g. insulin is derived from proinsulin by proteolytic removal of a peptide
zymogen: pepsinogen
- site of synthesis: stomach
- active enzyme: pepsin
zymogen: chymotrypsinogen
- site of synthesis: pancreas
- active enzyme: chymotrypsin
zymogen: trypsinogen
- site of synthesis: pancreas
- active enzyme: trypsin
secretion of zymogen granular by a cell of the pancreas
- darker-staining cells form clusters -> acini
- arranged in lobes separated by thin fibrous barrier
- secretory cells of each acinus surround small intercalated duct
- these cells have many small granules of zymogens
coagulation (clotting)
- blood changing from liquid to gel -> forming blood clot
- leads to hemostasis
- involves cellular (platelet) and protein (coagulation factor) component
hemostasis
cessation of blood loss from damaged vessel
mechanism of coagulation involves
- activation
- adhesion
- aggregator of platelets
- deposition and maturation of fibrin
blood leaking through endothelium starts 2 processes
- changes in platelets
2. exposure of sub endothelial tissue factor to plasma Factor VII -> leads to fibrin formation
primary hemostasis
platelets forming plug at injury site
secondary hemostasis
- occurs simultaneously
- additional coagulation factors (clotting factors) beyond Factor VII respond in a complex cascade to form fibrin strands -> strengthen platelet plug
coagulation factors
- serine proteases (enzymes) which act by cleaving downstream proteins
- circulate as inactive zymogens
coagulation cascade divided into 3 pathways
- tissue factor pathway (extrinsic)
- contact activation pathway (intrinsic)
- final common pathway
which pathways activate the final common pathway (factor x), thrombin and fibrin?
tissue factor and contact activation pathway
cofactors necessary for proper functioning of coagulation cascade
- calcium and phospholipid
- Vitamin K
procoagulant
?
anticoagulant
??
coagulation cascade
blood clotting mediated by cascade of proteolytic activations that ensure a rapid and amplified response to trauma
collagen
- fibrous protein
- major constituent of skin and bone
- derived from procollagen (soluble precursor)
many developmental processes are controlled by activation of zymogens. T/F?
True
- e.g. large amounts of collagen resorbed from tail of tadpole -> metamorphosis into frog
- e.g. conversion of procollagenase into collagenase (active protease)
apoptosis
- programmed cell death
- mediated by proteolytic enzymes -> capsases
- produces special cell fragments -> phagocytic cells
- can’t stop once it starts
- initiated through 1 of 2 pathways: intrinsic and extrinsic pathway
- both pathways use caspases (proteases)
capsases
- proteolytic enzymes that mediate apoptosis
- synthesized in precursor form as procaspases
- when activated, function to cause cell death
some enzymes with specialized regulatory functions can be regulated when physiologic conditions change, by:
- regulation of allosteric enzymes
- regulation of enzymes by covalent modification
- induction and repression of enzyme synthesis
allosteric enzymes
- consist of multiple subunits
- regulated by effectors (modifiers) that bind noncovalently at a site other than the active site altering the affinity of the enzyme for its substrate or modifying the maximal catalytic activity of the enzyme
- can increase of decrease affinity for substrate
positive effector/negative effector
- effectors can influence affinity of enzyme for its substrate K0.5
- modify maximal catalytic velocity Vmax
- or both
homotropic effectors
- when substrate itself serves as an effector
- most allosteric enzymes serve as positive homotropic effectors:
- presence of substrate molecule at one site of the enzyme enhances the catalytic properties of the other substrate-binding sites
- ex: hemoglobin is a homotropic allosteric protein
hemoglobin
- sigmoidal shape -> subunits cooperate in binding oxygen
- binding of oxygen molecule increases the oxygen affinity of the remaining heme groups in the same hemoglobin molecule (homotropic effector)
other allosteric effects found in hemoglobin
- caused by pH, pCO2 and the cocentration of 2,3-bisphosphoglycerate
- at high pO2, and high pH (such as in lungs): Hb has a very high affinity to oxygen
- at low pO2 and low pH (such as in tissues): Hb has a low affinity to oxygen, and releases oxygen to myoglobin and to tissue cells
2,3-bisphosphate
- generated from an intermediate of the glycolysis
- important regulator of binding of O2 to hemoglobin
- > allosteric effector
- binds to deoxyhemoglobin and decreases O2 affinity of hemoglobin
heterotropic effectors
- effector different from substrate
- ex: feedback inhibition of a metabolic pathway
covalent modifications
- addition or removal of phosphate groups from specific amino acids of the enzyme (Ser, Tyr, Thr)
- phosphorylation reactions are catalyzed by kinases using ATP as a phosphate donor