S1-L11: Enzymes 1 Flashcards
What are enzymes?
- large globular protein molecules
- biological catalysts–>speed up biological reactions without being used up
- enzymes show a lot of specificity
Why are enzymes important for humans?
- nearly every process in body dependent on enzymes
- ->respiration/ signalling/ digestion & DNA replication
How are enzymes diverse (usage) and which enzymes are involved?
- 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
Explain how enzymes work in terms of specificity/ active site and formation of ES complexes (figure 1)
- 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
Define:
1- activation energy
2- transition state
refer to figure 2 and figure 3
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
What happens when an ES complexes form?
- when substrate binds
- ->enzyme may stretch OR distort key bond AND weaken so less activation energy needed to break bond start of reaction
How does the lock and key enzyme model work?
-only correctly sized key (substrate) fits into key hole (a. site) of lock enzyme
How does the induced fit model for enzymes work? (figure 5)
- shape of active site not exactly complementary
- ->but change shape in specific substrate presence to become complementary
Explain how enzymes are powerful and highly specific
- enzymes specific in reactions catalyse AND their choice of reactants (substrate)
- enzymes normally only catalyse one reaction
How are enzyme reactions controlled?
- side reactions leading to harmful waste products rare in enzyme catalysed reactions
- ->so are controlled reactions
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)
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
What are conenzymes?
- catalytic activity of many enzymes dependent on small molecule presence called cofactors AND coenzymes
- ->generally execute chemical reactions amino acids unable to do
Define the following:
1-apoenzymes
2-haloenzymes
(figure 8)
1-enzymes without it’s cofactor
2-when enzyme has it’s cofactor
Describe cofactors and how they work (figure 9)
- 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
Brief co-enzymes and their function (figure 9)
- 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
Describe lysosomes and how they work
- lysosomes contain over 60 enzymes
- ->play central role as “waste disposal system”
- able to digest obsolete AND un-used materials in cytoplasm
How is synthesis of lysosomal enzymes controlled?
-by nuclear genes
Outline what lysosomal storage diseases are and how they arise
- 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
Explain what Hurler Syndrome is
- 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
What is the possible treatment for Hurlers syndrome?
- enzyme replacement therapy AND bone marrow replacement
- key note: one enzyme deficiency may lead to spectrum of effects (hence term syndrome)
Brief Niemann-Pick disease (figure 11)
- 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
Explain what Tay-Sachs disease is and how it works
- 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
What is the result of the absence of Hex-A (fatty substance) OR lipid (GM2 ganglioside)?- Tay Sachs disease
(refer to figure 12)
- accumulates abnormally in cells
- ->especially nerve cells of brain
- ->on-going accumulation causes progressive damage to cells
Outline the Homocystinuria disease and how it develops
figure 13
- 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
State the symptoms of Homocysturia (figure 14)
- dislocation of lenses in eye
- near sightedness
- abnormal blood clots
- osteoporosis (weakening of bones)
- learning disabilities
- developmental problems
Outline the 6 different types of enzymes
- oxidoreductases
- transferases
- hydrolases
- lysases
- isomerases
- ligases
- figure 15 shows their distribution
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
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
State the function of each of the following oxidoreductases:
1-Hydroxylases 2-Oxidases 3-Peroxidases 4-Reductases 5-Oxygenase's 6-Dehydrogenases
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-)
What is the role of transferases?
- these enzymes catalyse functional group movement from one molecule to another
- these functional groups v. diverse can include
- ->phosphate/ methyl and glycosyl groups
Outline an example of transferases (figure 16)
-kinases- transferases which catalyse transfer of phosphate groups to specific substrates (phosphorylation)
What may be consequences of deficiencies in transferases?
-can lead to spectrum of diseases
State the function of lyases and how they work (figure 17)
- catalyse breaking (elimination reactions) of various chemical bonds
- they form new double bonds OR new ring structure
How do Isomerases work? (figure 18)
- catalyse structural changes within molecule
- only one substrate AND one product with nothing gained OR lost
- ->so represent only change in shape
Explain how ligases work and outline an example (figure 19)
- 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
Brief the way Hydrolases work
- catalyse hydrolysis; breaking of single bond via addition of water
- huge variety of hydrolase enzymes
- ->like digestive enzymes which classified based on their target
Outline each of the following classifications of hydrolases:
1-Proteases/peptidases
2-Lipases
3-Nucleases
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
