Exam 3: Lecture 18 Flashcards
Sir Archibald Edward Garrod
- First to make connection between disease and fundamental errors in biochem reactions
- Coined term “inborn errors of metabolism”
- Enzymes must be link, mutations can cause altering biochem reactions
Definition of enzyme
- A protein that speeds up a chemical reaction in a living organism
- acts as a catalyst for specific chemical reactions, converting substrates to products
_______ cleave peptide bonds at specific sites
•Proteases
Active Site
- Usually void of water
* controls the proper shape, pH, and polarity for substrate binding and chemical reactivity
Transition state
•Unstable and highest level of free energy
Small molecules that contribute to the chemical reaction of the enzyme are?
- Cofactors
- many different roles in catalysis
- enzymes that use the same cofactor share similar mechanisms of catalysis
Apoenzyme
•Enzyme without its cofactor
Haloenzyme
•Cofactor bound and catalytically active
Types of Cofactors
- Metals: + charges, stable coordination of active site groups, contribute to chemical reactivity.
- Coenzymes: small organic molecules often derived from vitamins
Coenzymes that are tightly bound are called?
•Prosthetic groups
Scurvy
- Cofactor deficiencies: Vit C cofactor for lysyl hydroxylase-involved in collagen assembly
- Spongy gums, hemorrhaging of skin and mucous membranes
Ariboflavinosis
- Cofactor deficiency: Riboflavin (B2) required fro FAD synthesis
- Reduced glutathione reductase activity (cleans up reactive oxygen species)-requires FAD
Lesions in corner of mouth and on lips, UV sensitive
Active site of alcohol dehydrogenase
- NAD+ is reduced to NADH in the conversion of ethanol to acetaldehyde
- The cofactos NAD+ and Zinc are in a specific arrangement for this catalysis
What are the 6 classes of enzymes and their type of reaction?
- Oxidoreductases: oxidation-reduction
- Transferases: group transfer
- Hydrolases: Hydrolysis reaction (transfer of functional groups to water)
- Lyases: Addition or removal of groups to form double bonds
- Isomerases: Isomerization (intramolecular group transfer)
- Ligases: Ligation of two substrates at the expense of ATP hydrolysis
Oxidoreductases
- Enzyme that catalyzes the transfer of electron from one molecule to another
- Reductant = hydrogen or e- donor
- Oxidant = hydrogen or e- acceptor
Alcohol Dehydrogenases (ADH)
- oxidorgenase that converts alcohols to aldyhydes or ketones with the reduction of NAD+ to NADH
- Alcohol = oxidized
- NAD+ = reduced
Transferases
- Donor molecules required (source of methyl groups for ATP)
- Kinases Receptors: phosphorylate proteins and themselves
- usually at tyrosine (TKRs), serine, and threonine residues
Hydrolases
- Hydrolysis of covalent bonds
* transfer function groups to water
What hydrolases cleave double sugars to single?
- Disaccharidases
* Defect in lactase = lactose intolerance
Lyases
- Addition or removal of double bonds
* Aldolase: catalyzes second step of glycolysis
Isomerases
- intramolecular group transfer
* produce is an isomer of the substrate
Triose phyosphate isomerase
- intramolecular oxidation-reduction reaction
- Glu 165 acts as a base/oxidant
- His 95 acts as acid/reductant
Ligases
- enzymes that catalyzes the covalent linkage of two substrates
- usually at the expense of ATP hydrolysis
DNA Ligase
- forms two covalent phosphodiester bonds between 3’ hydroxy ends of one nucleotide with the 5’ phosphate end of another
- uses ATP
