enzymes and co-enzymes and their mechanisms Flashcards
importance of enzymes
- natures catalyst and carry out all reactions of a cell
- many inherited diseases are caused by mutations in key enzymes
- -used commercially in food products and detergents
- used in drug synthesis to produce single isomer drugs
what can be used to diagnose disease
measurement of certain enzymes in the blood
catalysts..
reduce activation energy–> however they do not change the energy of a reaction
catalysts cannot..
make a thermodynamically unstable reaction become favourable i.e. they do not change the position of the equilibrium by they do speed up how quickly the reaction reaches equilibrium
for a reaction to be favourable
the pro cuts must be of lower energy than the reactants
speed of a reaction is determined by
activation energy
role of enzymes as catalysts
- provide a specific environment for the substrate where the reaction is more favourable
- the pocket on the enzyme where this occurs is called the active site
- enzymes lowers the energy needed to carry out the reaction
- enzyme is not used up in this process
- accelerates the conversion of s–> p (also p–>s)
- ES and EP are reaction intermediates
breakdown of enzymes catalysing s–>p
E+S ES ES(Transition state)EPE+P
what is bad for catalysis
tight binding to either the substrate or product is bad for catalysis - it is the transition state that enzymes bind tightly to
what are enzymes pockets or active sister designed to complement
the reaction transition state
what forces stabilise ES, ES (TS) and EP complexes?
the same as those forces that stabilise proteins e.g. H bond Hydrophobic, ionic, van der waaal.
enzyme is complimentary to..
transition state
in some enzymes..
a transient covalent bond is formed during the reaction
the energy derived from complex format is..
binding energy
co -enzyme
non-protein organic molecules required for catalysis eg. biotin, NAD+, FAD
co-factors
inorganic substances that are required for catalysis e.g. metal ions
what is a combination protein and coenzyme/cofactor called
holoenzyme
holoenzyme
what is a combination protein and coenzyme/cofactor called
the protein alone without the co-enzyme/cofactor
apoenzyme
apoenzyme
the protein alone without the co-enzyme/cofactor
who to coenzymes and cofactors help catalysis
they allows enzymes to access chemistries that are unavailable to amino acid side chains
what can occur if there are deficiencies in certain co-enzymes
disease
e.g. what co-enzymes and cofactors are deficient in megaloblastic aneomia
folic acid
what co-enzymes and cofactors are deficient in Beriberi
thiamine deficiency
what co-enzymes and cofactors are deficient in pellagra
nicotinamide deficiency/ nicotinic acid
6 main enzyme groups
- oxidoreductase
- transferase
- hydrolase
- lyase
- isomerase
- ligase
oxidoreductase
oxidation/redution reaction in which oxygen and hydrogen are gained or lost
transferase
transfer of functional groups such as amin groups, acetyl groups or phosphate group
hydrolase
hydrolysis
lyase
removal of groups of atoms without hydrolysis
isomerase
rearrangement of atoms within a molecule
ligase
joining of two molecules- using the energy derived from the break down of ATP
enzyme mechanism x3
- general acid-base catalyst
- metal ion catalysis
- covalent catalysis
general ace-base catalysts
enzymes stabilise unstable charged intermediates by transferring protons to and from the intermediate - therefore decreasing free energy of the transition state
e.g. amino acid side chains act as week proton donor and acceptors e.g. Gaul, lys (acids and bases)
Metal ion catalysis
ionic interactions between the enzyme bund metal and substrate can:
1_ orient a substrate for reaction
2_ stables charged reaction states
3_ mediate oxidation- reduction reactions
1/3rd of all known enzymes require a metal for catalytic activity
covalent catalysis
formation of transient covalent bods between enzymes and substrate- covalent complex undergoes a reaction to generate free enzymes.
- in comparison with the uncatalysed reaction, the formation of the covalent bond with the enzyme alter the pathway of the reaction and offers an alternative route to the same product that has a lower activation energy
what are serine proteases
a large family of enzymes that include digestive enzymes like trypsin and chymotrypsin, and the blood clotting enzyme thrombin.
These are ENDOPROTEASES WHICH HYDROLYSE PEPTIDE BONDS (AMIDE)
What catalytic triad to serine proteases have in their active sites
histidine, aspartate, serine
examples of serine proteases
trypsin chymotrypsin thrombin (blood clotting)
what sort of enzyme mechanisms to protease ue
a mixture of acid-base and covalent catalysis
-serine residue acts as a the nucleophile and is made more nucleophilic by histidine and aseptic acid
6 steps of protease mechanism
1) ES complex (michaelis)
2) first TS- tetrahedral intermediate
3) acyl enzyme intermediate
4) acyl enzyme water complex
5) second TS- tetrahedral intermediate
6) free enzyme
serine protease specificity
each enzyme has a different specificity pocket
specificity of trypsin
cleaves after Arg and Lys residues and has an Asp residue at the bottom of the binding pocket
specificity of chymotrypsin
cleaves after aromatic residues and has a neutral charged serine at the binding pocket
specificity of elastase
cleaves small hydroponic residues eg. glycine, alanine and valine
Metal ion catalysis
metal atoms are utilised by enzymes as co-factors.
-metals have the ability to lose electrons very easily.
Therefore this allows them to:
1) stabilise transient and intermediate structures in the AS
2) assist in forming strong nucleophile species
3) hold substrate in place
covalent catalysis explained
- many enzymes contain catalytic residues–> responsible for forming a temporary covalent bond with the substrate
- this keeps the substrate molecule inside the AS
- at the end of the reaction this covalent bond is broken to regenerate the free enzyme
acid base catalysis
- transfer of protons
- there are specific residues in the active site which will be involved e.g. Histidine used t transfer protons
By transferring H+ ion:
1) activate strong nucleophile required in catalysis
2) stabilise charged groups
3) increase electric interaction that may stabilise the transition state
