An enzyme is a protein that presents active sites which perform reactions by decreasing the activation energy of that reaction.
- Complex protein and biocatalyst (catalyst of biological origin)
- Remains unchanged after the reaction
- Identified by the presence of the suffix “-ase” (e.g., lactate dehydrogenase)
- Highly specific for particular substrates and products
- Substrate (S): a substance upon which the enzyme acts
- Enzyme-substrate (ES) complex: temporary molecule formed by the non-covalent binding of the enzyme and substrate via:
- Ionic interactions: connections between charged molecules
- Hydrophobic interactions
- Van der Waals forces: weak intermolecular attractions between uncharged molecules
- Hydrogen bonding
- Product (P): molecule created by the enzymatic reaction
- PH and temperature may alter its functions.
- Area of an enzyme that binds to specific substrate molecules in order to facilitate a reaction
- Consists of binding and catalytic sites
- Binding sites: the area where the the substrate binds
- Catalytic site: the area that reduces the activation energy (energy required for a reaction to proceed)
- Substrate specificity: Each enzyme can convert only one particular substrate. This is based on the “induced-fit” model, in which the binding site of the enzyme changes to match a particular substrate.
- Stereospecificity: Substrates must be a specific isomer (e.g., lactate dehydrogenase can only convert L-lactate to pyruvate and not its mirror image, D-lactate).
- Group specificity: Enzymes react with a specific chemical group (e.g., an amino group) located on the substrate.
- Reaction specificity: Each enzyme can catalyze only a specific type of reaction (e.g., hydrolysis).
The first part of the name describes the substrate. The last part describes the enzyme function. The first part will describe the product if the following are true:
- The product is biochemically important (e.g., pyruvate kinase).
- The enzyme is in the ligase category outlined in the table below (e.g., glutamine synthetase).
- An enzyme with the same function already exists and acts upon the substrate (e.g., pyruvate dehydrogenase and lactate dehydrogenase).
|Main group||Catalytic reaction||Important subclasses (examples)|
|Oxidoreductases||Transfer of reduction equivalents (1 mole of electrons); the electron donor is oxidized and increases its charge, the electron acceptor is reduced and decreases its charge||Dehydrogenases (alcohol dehydrogenase), oxidases (xanthine oxidase), reductases (glutathione reductase)|
|Transferases||Transfer of entire groups (e.g., amino groups)|
|Hydrolases||Molecular fission with water addition = hydrolytic fission|
|Lyases||Break bonds between 2 carbons, or a carbon atom and oxygen, or carbon and sulfur|
|Isomerases||Conversion of isomeric molecules into each other without changing the molecular formula||Cis-trans isomerases (peptidyl-prolyl cis-trans isomerase, phosphoglucoisomerase)|
|Ligases||Also called synthetases, energy-dependent linkage of compounds (e.g., dependent on ATP)|
Isoenzymes, Coenzymes, and Prosthetic Groups
Enzymes can be modified in common ways to allow different organs to have the same activities or for substances outside of the substrate/enzyme/product sequence to influence enzymes.
- Catalyze the same kinds of reactions, but differ slightly in their structure (different amino acid sequence) and in the organs on which they act (glycogen phosphorylase in the muscles vs. α-glucosidase in the heart)
- Small auxiliary molecules often needed to start the enzymatic reaction
- These molecules have the capacity to attach/detach to the enzyme.
- Serve a variety of functions (electron transfer, transfer of organic materials)
- Vitamins often serve as precursors to many organic cofactors.
|Coenzyme||Associated vitamin||Reaction type||Enzyme examples|
|Thiamine pyrophosphate||B1||Oxidative decarboxylation|
|FAD/FADH2||B2||Electron transfer||Succinate dehydrogenase|
|NAD+/NADP+||B3||Electron transfer||Many dehydrogenases|
|Lipoamide||B4||Oxidative decarboxylation||Pyruvate dehydrogenase|
|Coenzyme A (CoA)||B5||Acyl group transfer||α-ketoglutarate dehydrogenase|
|Pyridoxal phosphate||B6||Transamination||Alanine transaminase (ALT)|
|Biotin||B7||Carboxyl group transfer||Pyruvate carboxylase|
|Tetrahydrofolate (THF)||B9||Transfer of C1 groups|
|5-deoxyadenosyl cobalamin||B12||Intramolecular rearrangements|
- Specific non-polypeptide units firmly bound to the enzyme and required for the biological function of some enzymes
- These molecules are permanently attached to the enzyme.
The following conditions are caused by an enzymatic deficiency:
- Glucose-6-phosphate dehydrogenase deficiency: inherited in an X-linked recessive manner. Can cause episodic intravascular hemolytic anemia when triggered by infections, certain medication, stress, or foods such as fava beans, with all the symptoms and signs of hemolytic anemia such as jaundice, pallor, dyspnea, fatigue, and tachycardia. It can also produce neonatal jaundice in newborns.
- Galactosemia: most common and severe form of galactosemia. Produced due to a deficiency of galactose-1 phosphate uridyltransferase. Presents days after birth with clinical manifestations such as lethargy, failure to thrive, jaundice, and other features of liver injury
- Chronic granulomatous disease: chronic disorder characterized by granuloma formation. Phagocytic cells are unable to produce bactericidal superoxide due to a defect in the nicotinamide adenine dinucleotide phosphate oxidase in the cells.
- Lysosomal storage diseases: a group of genetic metabolic disorders caused by lysosomal defects that result in an accumulation of undigested metabolites and cellular death
- Gaucher’s disease: inherited disorder that leads to the accumulation of undegraded glycolipid substrates in cells due to a deficiency of acid β-glucosidase
- Krabbe’s disease: Also known as globoid cell leukodystrophy, this condition is produced due to a deficient activity of the galactocerebrosidase, which produces an accumulation of galactosylceramide.
- Tay-Sachs disease: Produced due to a deficiency of hexosaminidase A, this autosomal recessive lipid storage disorder may cause blindness, hypotonia, progressive cognitive decline, and seizures.