S1-L11: Enzymes 1

Question 1

What are enzymes?

Answer 1

• large globular protein molecules
• biological catalysts–>speed up biological reactions without being used up
• enzymes show a lot of specificity

Question 2

Why are enzymes important for humans?

Answer 2

• nearly every process in body dependent on enzymes

- ->respiration/ signalling/ digestion & DNA replication

Question 3

How are enzymes diverse (usage) and which enzymes are involved?

Answer 3

• digestion/DNA synthesis/ cell signalling/ respiration/ metabolism/ cell movement & growth/ cellular digestion/ immunology/ CO2 transport/ vascular tone control/ control of neuronal pathways
• enzymes involved in these processes include:
• ->amylase/ protease/ lipase

Question 4

Explain how enzymes work in terms of specificity/ active site and formation of ES complexes (figure 1)

Answer 4

• enzymes selective in substrate bind to due to enzyme active site
• a. site: region where substrate molecules bind AND undergo chemical reaction
• ->bring together substrates in enzyme-substrate (ES) complexes
• catalytic powers comes from binding their substrates together in orientation which promotes transition states formation

Question 5

Define:

1- activation energy
2- transition state

refer to figure 2 and figure 3

Answer 5

1-In chemical reaction is measure of energy needed for conversion of substrate to reactive state
2-highest potential E along reaction coordinate
–>point of no return where reactant molecules go on to form products

Question 6

What happens when an ES complexes form?

Answer 6

• when substrate binds

- ->enzyme may stretch OR distort key bond AND weaken so less activation energy needed to break bond start of reaction

Question 7

How does the lock and key enzyme model work?

Answer 7

-only correctly sized key (substrate) fits into key hole (a. site) of lock enzyme

Question 8

How does the induced fit model for enzymes work? (figure 5)

Answer 8

• shape of active site not exactly complementary

- ->but change shape in specific substrate presence to become complementary

Question 9

Explain how enzymes are powerful and highly specific

Answer 9

• enzymes specific in reactions catalyse AND their choice of reactants (substrate)
• enzymes normally only catalyse one reaction

Question 10

How are enzyme reactions controlled?

Answer 10

• side reactions leading to harmful waste products rare in enzyme catalysed reactions
• ->so are controlled reactions

Question 11

Outline the specific function of each of the following example enzymes and why they are specific:

1-Proteolytic enzymes (figure 6)
2-Trypsin
3-Thrombin (figure 7)

Answer 11

1-break proteins down
2-digestive enzyme- only splits bonds between lysine AND arginine residue
3-catalyses hydrolysis OR Arg- Gly only in specific chain of residue

• specific due to precise interaction of substrate with enzyme
• ->result of intricate 3D enzyme structure

Question 12

What are conenzymes?

Answer 12

• catalytic activity of many enzymes dependent on small molecule presence called cofactors AND coenzymes
• ->generally execute chemical reactions amino acids unable to do

Question 13

Define the following:

1-apoenzymes
2-haloenzymes

(figure 8)

Answer 13

1-enzymes without it’s cofactor

2-when enzyme has it’s cofactor

Question 14

Describe cofactors and how they work (figure 9)

Answer 14

• simple inorganic ions which promote enzyme function–> like Zn/Cu/ Fe
• make it fold + create an a. site
• enhances charge in a. site to improve substrate binding
• ->like amylase requires chloride ions

Question 15

Brief co-enzymes and their function (figure 9)

Answer 15

• small organic molecules attach to activate enzyme AND detach when reaction completed to deactivate enzyme
• most often these are vitamin like Niaci/ riboflavin
• coenzymes act as transporters of chemical groups from one reactant to another

Question 16

Describe lysosomes and how they work

Answer 16

• lysosomes contain over 60 enzymes
• ->play central role as “waste disposal system”
• able to digest obsolete AND un-used materials in cytoplasm

Question 17

How is synthesis of lysosomal enzymes controlled?

Answer 17

-by nuclear genes

Question 18

Outline what lysosomal storage diseases are and how they arise

Answer 18

• mutations in genes for lysosomal enzymes responsible for more than 30 different human genetic disorders
• ->known as lysosomal storage diseases
• these diseases result from accumulation of specific substrates due to inability to break them down

Question 19

Explain what Hurler Syndrome is

Answer 19

• lysosomal storage disease
• deficiency in enzyme iduronidase–> responsible for degradation mucopolysaccharide in lysosomes
• ->longer chain sugar molecules build up- so found in nucleus AND fluid around joint
• ->leads to abnormal bone structure AND development delay

Question 20

What is the possible treatment for Hurlers syndrome?

Answer 20

• enzyme replacement therapy AND bone marrow replacement

- key note: one enzyme deficiency may lead to spectrum of effects (hence term syndrome)

Question 21

Brief Niemann-Pick disease (figure 11)

Answer 21

• inherited disease which affects lipid metabolism
• lack sphingomyelinase (ASM)
• ->this lysosomal enzyme needed to metabolise lipid sphingomyelin
• if ASM absent OR not functioning properly sphingomyelin accumulates within cell
• ->eventually causes cell death AND malfunction of major organ systems

Question 22

Explain what Tay-Sachs disease is and how it works

Answer 22

• functional Hexosaminidase-A absent from lysosomes
• ->progressive deterioration of nerve cells AND of mental + physical abilities (starts around 6 months of age)
• ->results in death by approx age 4

Question 23

What is the result of the absence of Hex-A (fatty substance) OR lipid (GM2 ganglioside)?- Tay Sachs disease

(refer to figure 12)

Answer 23

• accumulates abnormally in cells
• ->especially nerve cells of brain
• ->on-going accumulation causes progressive damage to cells

Question 24

Outline the Homocystinuria disease and how it develops

figure 13

Answer 24

• mutations in Cystathionine beta-synthase gene causes most common form of homocysturia
• CBS–>enzyme responsible for converting amino acid homocysteine to cystathionine
• ->result of this is other amino acids including methionine produced
• mutation in CBS prevent homocysteine being used properly
• ->result- this amino acid + other toxic by-prouct substances build up in blood
• normally a. acids produced from protein breakdown which not needed removed from body
• babies with HCU unable to breakdown methionine
• ->can be harmful

Question 25

State the symptoms of Homocysturia (figure 14)

Answer 25

• dislocation of lenses in eye
• near sightedness
• abnormal blood clots
• osteoporosis (weakening of bones)
• learning disabilities
• developmental problems

Question 26

Outline the 6 different types of enzymes

Answer 26

• oxidoreductases
• transferases
• hydrolases
• lysases
• isomerases
• ligases
• figure 15 shows their distribution

Question 27

What reactions are catalysed by each of the six different enzyme classes (also give examples)?:

1-Hydrolase 
2-Isomerase 
3-Lyase
4-Oxidoreductase
5-Synthetases 
6-Transferase

Answer 27

1-hydrolysis (catabolic)–>lipase/ proteins
2-rearrangement of atoms in molecule–> phosphohexoisomerase
3-splitting chemicals into smaller parts without water use (catabolic)–>decarboxylase/ aldolases
4-transfer e-‘s/ H atoms one molecule to another–> dehydrogenases/oxidases
5-joining of two molecules by new bond formation (anabolic)–>DNA ligase/ DNA polymerase
6-moving functional group one molecule to another–> kinases/ transaminases

Question 28

State the function of each of the following oxidoreductases:

1-Hydroxylases 
2-Oxidases
3-Peroxidases 
4-Reductases 
5-Oxygenase's
6-Dehydrogenases

Answer 28

1-add hydroxyl groups to substrate
2-intramolecular O is the H or e- acceptor
3-reduction of hydrogen peroxide AND organic hydroperoxides
4-catalyse reductions
5-incorporate intramolecular oxygen into organic substrates
6-oxidise substrate by transferring one or more hydride ions (H-)

Question 29

What is the role of transferases?

Answer 29

• these enzymes catalyse functional group movement from one molecule to another
• these functional groups v. diverse can include
• ->phosphate/ methyl and glycosyl groups

Question 30

Outline an example of transferases (figure 16)

Answer 30

-kinases- transferases which catalyse transfer of phosphate groups to specific substrates (phosphorylation)

Question 31

What may be consequences of deficiencies in transferases?

Answer 31

-can lead to spectrum of diseases

Question 32

State the function of lyases and how they work (figure 17)

Answer 32

• catalyse breaking (elimination reactions) of various chemical bonds
• they form new double bonds OR new ring structure

Question 33

How do Isomerases work? (figure 18)

Answer 33

• catalyse structural changes within molecule
• only one substrate AND one product with nothing gained OR lost
• ->so represent only change in shape

Question 34

Explain how ligases work and outline an example (figure 19)

Answer 34

• responsible for catalysis of ligation–>joining of two substances
• usually potential energy needed
• ->so reaction couples to hydrolysis of diphosphate bond in nucleotide triphosphate like ATP
• example: DNA ligase
• ->closes “breaks” in broken DNA fragments

Question 35

Brief the way Hydrolases work

Answer 35

• catalyse hydrolysis; breaking of single bond via addition of water
• huge variety of hydrolase enzymes
• ->like digestive enzymes which classified based on their target

Question 36

Outline each of the following classifications of hydrolases:

1-Proteases/peptidases
2-Lipases
3-Nucleases

Answer 36

1-cleave (split/sever) peptide bonds between a. acids to break proteins down
2-break down lipids into fatty acids AND glycerol by cleaving ester bonds
3-cleave phosphodiester bonds between nucleotide subunits in nucleic acids
–>termed “exo” or “endo” depending on where cut
–>endo cut middle of chain BUT exo enzymes cut end of chain to release individual monomer