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

• what are the 2 types

• 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

how much does proximity increase rate by

10 5 to 10 8

how much does orientation increase rate by

10 4

how much does microenvironment increase rate by

10 4

what is the cofactor for pyruvate dehydrogenase required for the formation of acetyl coenzyme a

thiamine

what is the cofactor for methylmalonyl coa isomerase require to ensure the entry of proionate into the citric acid cycle

cobalamin

b12

deficiency leads to pining or moor sickness

what coenzyme is often covalently liked to adenosine

niacine

b3

what is an example of a protein that bidns calcium through ef hand

calmodulin and troponin c