Enzymes: characteristics and history

• Enzymes are proteins that are folded into specific shapes.
• Enzymes are biological catalysts.
• Catalysts speed up chemical reactions.
• Enzymes are not permanently changed during a process.

Enzyme Characteristics

• Enzymes accelerate chemical reactions.
• Enzymes can perform multiple reactions as they are recycled.
• The final distribution of reactants and products is governed by equilibrium properties.
• Acting under mild conditions is an enzyme characteristic.
• Temperature and pressure are considered mild conditions.
• Enzymes are reusable.
• Enzymes are specific to substrates they catalyze.
• Most enzyme names end in "-ase".

Enzyme History

• French chemist Anselme Payen discovered the first enzyme, diastase, in 1833.
• Louis Pasteur thought fermentation was caused by a vital force called "ferments" within yeast cells.
• It was believed these ferments function only within living organisms.
• In 1877, German physiologist Wilhelm Kühne coined the term "enzyme."
• The word enzyme comes from the Greek word "ἔνζυμον" (enzymon), meaning "leavened" or "in yeast."
• Initially "enzyme" referred to nonliving substances, like pepsin, and "ferment" to chemical activity from living organisms.
• Eduard Buchner submitted a paper studying yeast extracts, finding sugar fermented without living yeast cells at the Berlin University in 1897.
• In 1907, Eduard Buchner received the Nobel Prize in Chemistry for discovering cell-free fermentation.
• The suffix "-ase" is combined with the substrate name or reaction type to name enzymes.
• Lactase cleaves lactose, and DNA polymerase forms DNA polymers.
• The biochemical identity of enzymes was unknown in the early 1900s.
• Some scientists thought proteins were carriers for true enzymes and proteins per se were unable to catalyze,.
• James B. Sumner showed that the enzyme urease was a pure protein, which he crystallized in 1926.
• Sumner also crystallized the enzyme catalase in 1937.
• John Howard Northrop and Wendell Meredith Stanley demonstrated that pure proteins can be enzymes.
• Northrop and Stanley worked on the digestive enzymes pepsin, trypsin, and chymotrypsin.
• In 1946, these three scientists were awarded the Nobel Prize in Chemistry.
• Crystallizing enzymes led to the discovery of their structure via X-ray crystallography.
• This was first done for lysozyme, found in tears, saliva, and egg whites, in 1965 by a group led by David Chilton Phillips.

Structures of Enzymes

• The active site of an enzyme binds substrates, cofactors, and prosthetic groups.
• The active site contains residues that help hold the substrate.
• Active sites usually occupy less than 5% of the total surface area of an enzyme.
• Active site has a specific shape, determined by the protein's tertiary structure.
• A change in the shape of the protein affects the shape of the active site and thus the enzyme's function.
• The active site has a binding site and catalytic Site.
• The binding site chooses the substrate and binds it to active site, while the catalytic site performs the catalytic action of the enzyme.
• A cofactor is a non-protein molecule that helps carry out chemical reactions that amino acids can't.
• Organic cofactors and inorganic cofactors are the two types of cofactors.
• Inorganic cofactors are inorganic molecules which are required for the proper activity of enzymes.
• Carbonic anhydrase requires Zn++ for activity; hexokinase needs Mg++.
• Organic cofactors are organic molecules required for enzyme activity.
• An example of an organic cofactor is that glycogen, phosphorylase, and pyridoxal phosphate.
• Prosthetic groups are tightly bound organic cofactors, while coenzymes are loosely bound organic cofactors.
• Examples of prosthetic groups include Flavin, heme groups, and biotin.
• Types of coenzymes include NAD+.
• An enzyme is termed an apoenzyme if the cofactor has been removed.
• A complete protein complex, including any small organic molecules, metal ions, or other components, is termed a holoenzyme or holoprotein.
• The reactant in a biochemical reaction is called a substrate.
• An enzyme-substrate complex forms when a substrate binds to an enzyme.
• Enzymes are synthesized by ribosomes attached to rough endoplasmic reticulum.
• The synthesis of enzymes is carried out by DNA.
• Amino acids are bonded together according to DNA codes, forming specific enzymes.

Properties of Enzymes

• Enzymes display high specificity due to the close fit between the substrate and the active site.
• Enzymes can increase reaction rates by over 10 million times.
• Most enzymes can process over 10,000 substrate molecules per second.
• Genes control the concentration and synthesis rate of enzymes.
• Enzyme activity can be inhibited or enhanced by substances.
• Active or inactive enzymes can be turned on or off by chemical surroundings.
• Inactive digestive enzymes in the stomach activate when hydrogen ions break bonds.
• A part of the molecule falls off, which exposes the active site.

Nomenclature of Enzymes

• Enzymes are named by the substrates they catalyze.
• The enzyme that catalyzes the hydrolysis is called hydrolase.
• Some enzymes named before systematic naming include pepsin, trypsin, and rennin.
• Adding the suffix "-ase" at the end of the substrate name is how enzymes are named.
• Maltase causes maltose + water to produce glucose + glucose.
• Lactase converts lactose into glucose + galactose, and maltase converts maltose into glucose.
• Cellulase converts cellulose into glucose, and lipase converts lipid into glycerol + fatty acid. Meanwhile, amylase converts starch into maltose, and protease converts protein into peptides + polypeptide.

Classification of Enzymes

• The International Enzyme Commission developed a systematic classification of enzymes.
• Classification is based on the reactions that enzymes catalyze.
• There are six major enzyme classes.
• Each class is further divided into sub-classes that describe enzyme-catalyzed reactions.
• Oxidoreductases catalyze reduction-oxidation (redox):.
• Lactate dehydrogenase is an example of oxidoreductase.
• Transferases move chemical groups, while hydrolases catalyze hydrolysis, or bond cleavage with the transfer of a water functional group.
• Hexokinase is a transferase, and lysozyme is a hydrolase.
• Lysases catalyze non-hydrolytic bond cleavage.
• Fumarase is an example of a lysase.
• Isomerases transfer intramolecular groups, while ligases catalyze the synthesis of new covalent bonds.
• Triose phosphate isomerase is an isomerase, and RNA polymerase is a ligase.

Function of Enzymes

• Enzymes weaken chemical bonds, which lowers the activation energy.
• Molecules can be built up or broken down by the body.

Enzyme-Substrate Complex

• The substance an enzyme acts on is the substrate.
• The lock and key analogy describes the substrate as the key and the enzyme as the lock.
• Emil Fischer proposed the lock and key model in 1894.
• According to the lock and key hypothesis, an enzyme's active site has a rigid shape.
• The active site doesn't change before or after a chemical reaction.
• The substrate is where the active site temporarily fits during the metabolic reaction.
• A change in the shape of an enzyme's active site is considered induced fit.
• The substrate induces active site shape change, involving H+ and ionic bonds.
• A substrate is thought to fit into an enzyme's active site like a key fits in a lock.

Factors Affecting Enzyme Activity

• Environmental conditions, cofactors & coenzymes, and enzyme inhibitors can all affect enzyme activity.
• Temperature, pH, and ionic concentration (salt ions) are environmental conditions.
• Extreme temperatures are most dangerous.
• High temperatures can denature (unfold) an enzyme, deactivating it.
• A pH near neutral has a range of approximately 6 to 8.
• Inorganic substances (zinc, iron) and vitamins are sometimes needed for proper enzymatic activity.
• Iron must be present in hemoglobin's quaternary structure to pick up oxygen.
• Two types of enzyme inhibitors are Competitive inhibitors and Noncompetitive inhibitors.
• Competitive inhibitors are chemicals that resemble an enzyme's normal substrate and compete for the active site.
• Noncompetitive inhibitors don't enter the active site, but bind somewhere else on the enzyme.
• This binding causes the enzyme to change shape, altering the active site.

Importance of Enzymes

• Enzymes are proteins in all living things, within cells or dissolved in surrounding fluids.
• Life would be impossible without the miracle of enzymes.
• Enzymes activate, inhibit, and control the body's entire metabolic process.
• The incredible energy that creates and maintains comes from enzymes.
• Metabolic, digestive, and food enzymes are the four types of enzymes.
• There are also macronutrients and micronutrients.
• Enzymes are regulated due to their important role in everyday life.
• Genetic disorders can result from the total absence or deficiency of one or more enzymes.
• Routine medical tests monitor enzyme activity in the blood to diagnose diseases.
• Many prescription drugs exert their effects through interactions with enzymes.
• Enzymes and their regulators are important tools in medicine, agriculture, and food science.