Enzyme

Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life.

An extreme example is orotidine 5'-phosphate decarboxylase, which allows a reaction that would otherwise take millions of years to occur in milliseconds.

By the late 17th and early 18th centuries, the digestion of meat by stomach secretions[8] and the conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified.

"[11] In 1877, German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme, which comes from Ancient Greek ἔνζυμον (énzymon) 'leavened, in yeast', to describe this process.

This was first done for lysozyme, an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965.

[20] Enzymes can be classified by two main criteria: either amino acid sequence similarity (and thus evolutionary relationship) or enzymatic activity.

Each enzyme is described by "EC" followed by a sequence of four numbers which represent the hierarchy of enzymatic activity (from very general to very specific).

[27] Enzyme denaturation is normally linked to temperatures above a species' normal level; as a result, enzymes from bacteria living in volcanic environments such as hot springs are prized by industrial users for their ability to function at high temperatures, allowing enzyme-catalysed reactions to be operated at a very high rate.

[31] Enzyme structures may also contain allosteric sites where the binding of a small molecule causes a conformational change that increases or decreases activity.

[32] A small number of RNA-based biological catalysts called ribozymes exist, which again can act alone or in complex with proteins.

Many enzymes possess small side activities which arose fortuitously (i.e. neutrally), which may be the starting point for the evolutionary selection of a new function.

[43] The active site continues to change until the substrate is completely bound, at which point the final shape and charge distribution is determined.

[44] Induced fit may enhance the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism.

For example, proteases such as trypsin perform covalent catalysis using a catalytic triad, stabilize charge build-up on the transition states using an oxyanion hole, complete hydrolysis using an oriented water substrate.

These cofactors serve many purposes; for instance, metal ions can help in stabilizing nucleophilic species within the active site.

These coenzymes cannot be synthesized by the body de novo and closely related compounds (vitamins) must be acquired from the diet.

To find the maximum speed of an enzymatic reaction, the substrate concentration is increased until a constant rate of product formation is seen.

Saturation happens because, as substrate concentration increases, more and more of the free enzyme is converted into the substrate-bound ES complex.

Example of such enzymes are triose-phosphate isomerase, carbonic anhydrase, acetylcholinesterase, catalase, fumarase, β-lactamase, and superoxide dismutase.

[70] Michaelis–Menten kinetics relies on the law of mass action, which is derived from the assumptions of free diffusion and thermodynamically driven random collision.

[82] A common example of an irreversible inhibitor that is used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin.

[83] As enzymes are made up of proteins, their actions are sensitive to change in many physio chemical factors such as pH, temperature, substrate concentration, etc.

Enzymes such as amylases and proteases break down large molecules (starch or proteins, respectively) into smaller ones, so they can be absorbed by the intestines.

In ruminants, which have herbivorous diets, microorganisms in the gut produce another enzyme, cellulase, to break down the cellulose cell walls of plant fiber.

Most central metabolic pathways are regulated at a few key steps, typically through enzymes whose activity involves the hydrolysis of ATP.

[91]: 141–48  Negative feedback mechanism can effectively adjust the rate of synthesis of intermediate metabolites according to the demands of the cells.

This helps with effective allocations of materials and energy economy, and it prevents the excess manufacture of end products.

Like other homeostatic devices, the control of enzymatic action helps to maintain a stable internal environment in living organisms.

Enzymes in general are limited in the number of reactions they have evolved to catalyze and also by their lack of stability in organic solvents and at high temperatures.

As a consequence, protein engineering is an active area of research and involves attempts to create new enzymes with novel properties, either through rational design or in vitro evolution.

Ribbon diagram of glycosidase with an arrow showing the cleavage of the maltose sugar substrate into two glucose products.
The enzyme glucosidase converts the sugar maltose into two glucose sugars. Active site residues in red, maltose substrate in black, and NAD cofactor in yellow. ( PDB : 1OBB ​)
IUPAC definition for enzymes
Photograph of Eduard Buchner.
Eduard Buchner
A graph showing that reaction rate increases exponentially with temperature until denaturation causes it to decrease again.
Enzyme activity initially increases with temperature ( Q10 coefficient ) until the enzyme's structure unfolds ( denaturation ), leading to an optimal rate of reaction at an intermediate temperature.
Lysozyme displayed as an opaque globular surface with a pronounced cleft which the substrate depicted as a stick diagram snuggly fits into.
Organisation of enzyme structure and lysozyme example. Binding sites in blue, catalytic site in red and peptidoglycan substrate in black. ( PDB : 9LYZ ​)
Hexokinase displayed as an opaque surface with a pronounced open binding cleft next to unbound substrate (top) and the same enzyme with more closed cleft that surrounds the bound substrate (bottom)
Enzyme changes shape by induced fit upon substrate binding to form enzyme-substrate complex. Hexokinase has a large induced fit motion that closes over the substrates adenosine triphosphate and xylose . Binding sites in blue, substrates in black and Mg 2+ cofactor in yellow. ( PDB : 2E2N ​, 2E2Q ​)
Thiamine pyrophosphate displayed as an opaque globular surface with an open binding cleft where the substrate and cofactor both depicted as stick diagrams fit into.
Chemical structure for thiamine pyrophosphate and protein structure of transketolase . Thiamine pyrophosphate cofactor in yellow and xylulose 5-phosphate substrate in black. ( PDB : 4KXV ​)
A two dimensional plot of reaction coordinate (x-axis) vs. energy (y-axis) for catalyzed and uncatalyzed reactions. The energy of the system steadily increases from reactants (x = 0) until a maximum is reached at the transition state (x = 0.5), and steadily decreases to the products (x = 1). However, in an enzyme catalysed reaction, binding generates an enzyme-substrate complex (with slightly reduced energy) then increases up to a transition state with a smaller maximum than the uncatalysed reaction.
The energies of the stages of a chemical reaction . Uncatalysed (dashed line), substrates need a lot of activation energy to reach a transition state , which then decays into lower-energy products. When enzyme catalysed (solid line), the enzyme binds the substrates (ES), then stabilizes the transition state (ES ‡ ) to reduce the activation energy required to produce products (EP) which are finally released.
Schematic diagram of the glycolytic metabolic pathway starting with glucose and ending with pyruvate via several intermediate chemicals. Each step in the pathway is catalyzed by a unique enzyme.
The metabolic pathway of glycolysis releases energy by converting glucose to pyruvate via a series of intermediate metabolites. Each chemical modification (red box) is performed by a different enzyme.
Ribbon diagram of phenylalanine hydroxylase with bound cofactor, coenzyme and substrate
In phenylalanine hydroxylase over 300 different mutations throughout the structure cause phenylketonuria . Phenylalanine substrate and tetrahydrobiopterin coenzyme in black, and Fe 2+ cofactor in yellow. ( PDB : 1KW0 ​)
Hereditary defects in enzymes are generally inherited in an autosomal fashion because there are more non-X chromosomes than X-chromosomes, and a recessive fashion because the enzymes from the unaffected genes are generally sufficient to prevent symptoms in carriers.