enzymes: classification, structure. accelerate reactions by a millions fold enzymes - catalysts of...
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ENZYMES: CLASSIFICATION, STRUCTUREENZYMES: CLASSIFICATION, STRUCTURE
Accelerate reactions by a millions fold
Enzymes - catalysts of biological reactions
1. Catalyze only thermodynamically possible reactions
2. Are not used or changed during the reaction.
3. Don’t change the position of equilibrium and direction of the reaction
4. Usually act by forming a transient complex with the reactant, thus stabilizing the transition state
Common features for enzymes and inorganic catalysts:
Specific features of enzymes:
1. Accelerate reactions in much higher degree than inorganic catalysts
2. Specificity of action
3. Sensitivity to temperature
4. Sensitivity to pH
Structure of enzymesEnzyme
sComplex or holoenzymes
(protein part and nonprotein part – cofactor)
Simple (only protein)
Apoenzyme (protein part)
Cofactor
Prosthetic groups
-usually small inorganic molecule or
atom;
-usually tightly bound to apoenzyme
Coenzyme
-large organic molecule
-loosely bound to apoenzyme
Example of prosthetic group
Metalloenzymes contain firmly bound metal ions at the enzyme active sites (examples: iron, zinc, copper, cobalt).
Example of metalloenzyme: carbonic anhydrase contains
zinc
Coenzymes
• Coenzymes act as group-transfer reagents
• Hydrogen, electrons, or groups of atoms can be transferred
Coenzyme classification
(1) Metabolite coenzymes - synthesized from common metabolites
(2) Vitamin-derived coenzymes - derivatives of vitamins
Vitamins cannot be synthesized by mammals, but must be obtained as nutrients
Examples of metabolite coenzymes
ATP
S-adenosylmethionine
ATP can donate phosphoryl group
S-adenosylmethioninedonates methyl groups in many biosynthesis reactions
Cofactor of nitric oxide synthase
5,6,7,8 - Tetrahydrobiopterin
Vitamin-Derived Coenzymes
•Vitamins are required for coenzyme synthesis and must be obtained from nutrients
•Most vitamins must be enzymatically transformed to the coenzyme
•Deficit of vitamin and as result correspondent coenzyme results in the disease
• Nicotinic acid (niacin) an nicotinamide are precursor of NAD and NADP
• Lack of niacin causes the disease pellagra
NAD+ and NADP+
NAD and NADP are coenzymes for dehydro-genases
FAD and FMN• Flavin adenine dinucleotide (FAD) and Flavin
mononucleotide (FMN) are derived from riboflavin (Vit B2)
• Flavin coenzymes are involved in oxidation-reduction reactions
FMN (black), FAD (black/blue)
Thiamine Pyrophosphate (TPP)
• TPP is a derivative of thiamine (Vit B1)
• TPP participates in reactions of: (1) Oxidative decarboxylation(2) Transketo-lase enzyme reactions
Pyridoxal Phosphate (PLP)
• PLP is derived from Vit B6 family of vitamins
PLP is a coenzyme for enzymes catalyzing reactions involving amino acid metabolism (isomerizations, decarboxylations, transamination)
Enzymes active sites
Active site – specific region in the enzyme to which substrate molecule is bound
Substrate usually is relatively small molecule
Enzyme is large protein molecule
Therefore substrate binds to specific area on the enzyme
Characteristics of active sites
Specificity (absolute, relative (group), stereospecificity)
Small three dimensional region of the protein. Substrate interacts with only three to five amino acid residues. Residues can be far apart in sequence
Binds substrates through multiple weak interactions (noncovalent bonds)
There are contact and catalytic regions in the active site
Active site of lysozym consists of six amino acid residues which are far apart in sequence
Active site contains functional groups (-OH, -NH, -COO etc)
Binds substrates through multiple weak interactions (noncovalent bonds)
Theories of active site-substrate interaction
Fischer theory (lock and key model)
The enzyme active site (lock) is able to accept only a specific type of substrate (key)
Koshland theory (induced-fit model)
The process of substrate binding induces specific conformational changes in the the active site region
Properties of Enzymes
Specificity of enzymes
1.Absolute – one enzyme acts only on one substrate (example: urease decomposes only urea; arginase splits only arginine)
2.Relative – one enzyme acts on different substrates which have the same bond type (example: pepsin splits different proteins)
3.Stereospecificity – some enzymes can catalyze the transformation only substrates which are in certain geometrical configuration, cis- or trans-
Sensitivity to pHEach enzyme has maximum activity at a particular pH (optimum pH)
For most enzymes the optimum pH is ~7 (there are exceptions)
-Enzyme will denature above 45-50oC
-Most enzymes have temperature optimum of 37o
Each enzyme has maximum activity at a particular temperature (optimum temperature)
Sensitivity to temperature
Naming of EnzymesCommon names
are formed by adding the suffix –ase to the name of substrate
Example: - tyrosinase catalyzes oxidation of tyrosine; - cellulase catalyzes the hydrolysis of cellulose
Common names don’t describe the chemistry of the reaction Trivial names
Example: pepsin, catalase, trypsin.
Don’t give information about the substrate, product or chemistry of the reaction
Principle of the international classification
All enzymes are classified into six categories according to the type of reaction they catalyze
Each enzyme has an official international name ending in –ase
Each enzyme has classification number consisting of four digits: EC: 2.3.4.2
First digit refers to a class of enzyme, second -to a subclass, third – to a subsubclass, and fourth means the ordinal number of enzyme in subsubclass
The Six Classes of Enzymes
1. Oxidoreductases
• Catalyze oxidation-reduction reactions
- oxidases - peroxidases - dehydrogenases
2. Transferases
•Catalyze group transfer reactions
3. Hydrolases
•Catalyze hydrolysis reactions where water is the acceptor of the transferred group
- esterases - peptidases - glycosidases
4. Lyases
•Catalyze lysis of a substrate, generating a double bond in a nonhydrolytic, nonoxidative elimination
5. Isomerases
•Catalyze isomerization reactions
6. Ligases (synthetases)
•Catalyze ligation, or joining of two substrates
•Require chemical energy (e.g. ATP)