enzymes

transition state

• old bonds are incompletely broken and new bonds are incompletely formed

• has a different geometry from either reactants or products

how do enzymes affect the transition state?

• proximity

• orientation

• microenvironment

cofactors

• a non protein compound that must be bound either tightly (prosthetic group) or loosely (coenzyme) to an enzyme in order for it to function during catalysis.

• eg metal ions

• many are vitamin derivatives, required in diet as not synthesised

• eg thiamine and cobalamin

coenzyme

• binds reversibly 

• they are chemically changed during the course of enzyme activity

• many are vitamin derivatives

feedback vontrol of enzyme pathways

• operate within pathwats

• many metabolic pathways areeeecontrolled by feedback mechanisms

allosteric enzymes

• close to beginning end or branch point of metabolic pathways

• bind products of remote reactions in the same or related pathway

• at allosteric site

• have a quaternary structure

• display s shaped kinetic profiles- cooperitivity

can be affected by inhibitors or activators

covalent modification

• phosphorylation/dephosphorylation

• phosphorylation- kinases

• de- phosphatases

• serine/threonine kinases and tyrosine kinases are the 2 types

• phosphorylation reactions usually requie ATP as a phosphate donor producing ADP in addition to covalently linking a phosphate group to serine threonine or tyrosine on the target protein

control by regulatory proteins or nucelotides

• enzymes can be activated or inhibited through binding of nucleotides or other proteins to site remote from active site

• eg regulatory subunit of cAMP dependent protein kinase requires nucleotide cAMP binding for activation

control by ion binding

• only calcium ions

• in an E-F hand the calcium binding site is located in a tight loop connecting two alpha helices E and F

control through proteolysis

• blood clotting pathway- protease cascade

• enzymes break down proteins to regulate cellular processes

• sequential activation of protease actiivty through proteolysis ensures rapid signal amplification

• mechanisms to stop protease is required

allosteric regulation of enzyme activity

• allosteric inhibitors stablise the inactive state

• so decreases affinity of enzyme for substrate

• allosteric activators stabilise the active site

• so incereases affinity of enzyme for substrate