Enzymes

Question 1

why are enzymes relevant to medicine?

Answer 1

drug action (drugs can be enzyme inhibitors e.g. penicillin)

biochemical defects in enzymes cause disease (some genetically inherited e.g. sex-linked recessive haemophillia)

chemical diagnosis/prognosis (enzymes useful indicators of tissue/organ damage during injury)

Question 2

how do enzymes work?

Answer 2

biological catalysts

specific action on substrate-specific active site

increase rate at which equilibrium is reached (dont change shift position of equilibrium as dont change concentrations of enzyme/substrate)

lower activation energy (reaction occurs at lower temp)

Question 3

how do enzymes lower activation energy?

Answer 3

providing chemically competent groups (amino acids side chains) that help make transition from A–> B

align substrates so that orientation is optimised for reaction

stabilising transition states of substrates- prevent them from turning back to substrate

Question 4

what is the active site of an enzyme?

Answer 4

region of enzyme which substrates binds and converted to product

3D structure made of crucial amino acid

binds via multiple weak interactions

complementary shape- gives specificity

Question 5

what is an enzyme assay?

Answer 5

measuring enzyme activity

procedure for measuring biochemical activity in a sample

Question 6

what is the Michealis-Menten model?

Answer 6

measure of enzyme affinity for its substrate

Question 7

what is the Michealis constant (km)

Answer 7

ratio of forward and backward reaction rate constants

Question 8

how does michealis constant (km) differ per enzyme?

Answer 8

fixed number dependent on individual enzyme

Question 9

how does the value of michealis constant (km) differ with enzyme affinity?

Answer 9

smaller km = higher affinity

Question 10

state the graphical/practical method of getting a value for km?

Answer 10

measure half Vmax

extrapolate down- gives km

Question 11

missed out km values from page 1 of introduction to enzymes

Answer 11

go back to this during revision

Question 12

which factors affect the rates of enzyme catalysed reactions?

Answer 12

substrate/enzyme concentration

temperature

pH- alteration in pH can ionise amino acid side chains which influence substrate binding, changing 3D structure of active site

inhibitors- natural/exogenous

Question 13

what is irreversible enzyme inhibition?

Answer 13

covalent modification of amino acid side chains in active site

(e.g. modification of active site on serine by nerve agents)

Question 14

what is reversible enzyme inhibition?

Answer 14

2 forms = competitive + non-competitive

Question 15

what is competitive enzyme inhibition?

Answer 15

substrate and inhibitor have similar structures + compete for active site of enzyme

Question 16

why are competitive enzyme inhibitors pharmacologically important?

Answer 16

most drugs that act on enzymes work this way

Question 17

how is competitive enzyme inhibition overcome?

Answer 17

by high substrate concentration

inhibitor only has limited chances to get into enzyme and block activity

Question 18

how does non-competitive enzyme inhibition happen?

Answer 18

inhibitor and substrate can simultaneously bind

binding occurs at independent sites
(substrate = active site, inhibitor = allosteric site)

inhibitor alters shape of active site

Question 19

how does a high substrate concentration affect non-competitive enzyme inhibition?

Answer 19

inhibition not affected

Question 20

what is the effect of competitive enzyme inhibition on a limeweaver-burk plot?

(what happens to the Vmax and Km?)

Answer 20

Vmax unchanged

Km increased

higher substrate concentration needed to reach rate of Vmax/2

Question 21

what is the effect of non-competitive enzyme inhibition on a limeweaver-burk plot?

(what happens to the Vmax and Km?)

Answer 21

Vmax decreased (proportion of enzymes switched off)

Km unchanged (substrate binding to uninhibited enzyme unaffected)

increasing substrate concentration = no effect

Question 22

what are co-factors for enzyme function?

Answer 22

metal ions or co-enzymes

components in active sites in some enzymes involved in REDOX reactions

Question 23

how do co-factors bind to enzymes?

Answer 23

electrical charge on metal involved in binding to -ve charged substrates

or

in stabilising negatively charged transition state

Question 24

give examples of enzyme cofactors

Answer 24

Cu3+, Zn2+, Fe3+, Mn2+, Mo4+ (occur naturally)

Question 25

what are coenzymes?

Answer 25

usually water soluble vitamins = essential coenzymes

carry reaction components

Question 26

give examples of co-enzymes

Answer 26

NADH carry electrons

coenzyme A carries acyl units

Question 27

which deficiency diseases are the following vitamins coenzymes for:

robiflavin (B2)
niacin
thiamine (B1)
vitamin C

Answer 27

robiflavin (B2) - ariboflavinosis

niacin - pellagra

thiamine (B1) - wernicke-korsakoff syndrome

vitamin C - scruvy

Question 28

which deficiency diseases are the following vitamins coenzymes for:

biotin
cobalamin
folic acid
pyridoxine 
pantothenic acid

Answer 28

biotin - nerve disorders

cobalamin - anaemia

folic acid - anaemia

pyridoxine - blood, skin and nerve changes

pantothenic acid - burning feet

Question 29

what is the effect of mutations in enzymes?

Answer 29

can cause metabolic defects

alter active site, regulatory site and junction between 2 polypeptides

Question 30

what is favism?

Answer 30

condition which occurs due to deficiency in glucose-6-phosphate (G6PDH)

Question 31

explain the biochemistry behind favism

Answer 31

G6PDH is used in first step of Pentose Phosphate Pathway (PPP)

produces ribose-5-phosphate (R5P) and NADPH

carriers of mutation in G6PDH have restricted ability to make NADPH

trigger haemolytic crisis and anaemia

Question 32

what are the symptoms of favism

Answer 32

haemolytic crises, jaundice = liver damage

crisis can be triggered by certain drugs, foods and infections (e.g. malaria)

Question 33

what is the prevalence rate and who is favism more common amongst?

Answer 33

> 400 million

african americans

southern mediterranean

kurdish