# Structural Biochemistry/Enzyme Catalytic Mechanism/Enzyme Classification/Lyases
## Overview

Lyases are enzymes that catalyze the cleavage of C-C, C-O, C-N bonds by other means than by hydrolysis or oxidation. These bonds are cleaved by the process of elimination and the resulting product is the formation of a double bond or a new ring. This class of enzymes differs from other enzymes in that two substrates are involved in one reaction direction, but only one substrate is involved in the other direction. To generate either a double bond or a new ring, the enzyme is acted upon the single substrate and a molecule is eliminated. Lyases can be seen in the reactions of the Citric Acid Cycle (Krebs cycle) and in glycolysis.
In glycolysis, the lyase called aldolase catalyzes the readily reversible splitting of fructose 1,6-bisphosphate (F-1,6-BP),into the products glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). This is an example of a lyase that helps to cleave carbon-carbon bonds.
A subclass of lyases is the Carbon-Carbon Lyases, which contain the decarboxylases, the aldehyde-lyases catalyzing the reversal of an aldol condensation, and the oxo-acid lyases catalyzing the cleavage of a 3-hydroxy acid, or the reverse reactions. Another subclass is the Carbon-Oxygen Lyases, which contain the hydro-lyases catalyzing the cleavage of C-O bonds by the elimination of water. Other C-O Lyases catalyze the elimination of an alcohol from a polysaccharide or the elimination of a phosphate. Carbon-Nitrogen Lyases are enzymes that release ammonia or its derivatives by forming a double bond or ring (CH-CH(-NH-R)- >C=CH- + NH2-R). Also, a specific enzyme, synthase, is responsible for catalyzing the synthesis process, and belongs to the class of Lyases that catalyze the reverse reaction.
Lyase also are enzymes that aid in breaking bonds, which often later result in the formation of a double bond or a cyclic structure by means of catalytic pathways. These types of reactions only calls for one molecule in the forward reaction, but needs two molecules for the reverse reaction.
An example of a lyase-catalyzed chemical reaction is a step in glycolysis: the formation of phosphoenolpyruvate from 2-phosphoglycerate, where dehydrations are involved to form the double bonds (refer to Bell p. 427 for diagram). The reaction, ATP > cAMP + PPi is catalyzed by the enzyme lyase.
Lyases cleave bonds in 6 different manners:
1) Carbon-Carbon bonds
2) Carbon-Oxygen bonds
3) Carbon-Nitrogen bonds
4) Carbon-Sulfur bonds
5) Carbon-Halide bonds
6) Phosphorous-Oxygen bonds
The means of this cleaving is through oxidation or hydrolysis. When acting on the single substrate, a molecule is eliminated and this generates a new double bond or a new ring. The naming of the group is formed according to 'substrate group-lyase'. For example, decarboxylase is a carbon-carbon lyase that adds or removes carboxyl groups from different organic compounds.
Example 1: Carbon-Carbon Lyases: These compounds contain decarboxylase, as explained above; aldehyde lyase which catalyzes the reverse reaction of aldol condensations; and oxo-acid lyases which catalyze the cleavage of many 3-hydroxy acids.
Example 2: Carbon-Oxygen Lyases: These enzymes catalyze the cleavage of a carbon-oxygen bond, as explained above. In hydro-lyases, this process is facilitated through the elimination of water; the same can be done by the elimination of alcohol groups as well as phosphate groups.
Example 3: Carbon-Nitrogen Lyases: This enzyme releases ammonia, while simultaneously forming a double bond or ring. Some of these enzymes can also catalyse the elimination of an amine or amide group. The following reaction is catalyzed by carbon-nitrogen lyase: CH-CH(-NH-R) > C=CH + NH2-R. Alternatively, the mechanism may also undergo the following reaction under carbon-nitrogen lyase enzyme: C(-OH)-CH(-NH2) > CH2-CO + NH3. Both illustrate the powerful cleaving ability of this enzyme at the carbon-nitrogen bond.
Example 4: Carbon-Sulfur Lyases: These enzymes work by eliminating or substituting dihydrogen sulfide (H2S) from a reaction.
Example 5: Carbon-Halide Lyases: This enzyme utilizes a mechanism which eliminates hydrochloric acid (HCl) from Dichloro-Diphenyl-Trichloroethane (DDT), a synthetic pesticide.
Example 6: Phosphorous-Oxygen Lyases: The enzyme eliminates diphosphate from nucleotide triphosphates such as ATP.
Lyase Deficiency Disorder
Lyase deficiency, also referred to as HMG-CoA lyase deficiency, is rare inherited disorder in which the body can't process the amino acid leucine. Also, the disorder prevents the body from synthesizing ketones, which are used for energy during periods where the body is without food. The condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition, but may be at risk of passing it onward to the next generation.
The symptoms of lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, lethargy, and weak muscular development. During a stint with the symptoms, blood sugar levels can become hypoglycemic, or very low, and a buildup of harmful compounds can cause the blood to become too acidic. If untreated, the disorder can lead to breathing problems, convulsions, coma, and even death. Infection, strenuous exercise, and other physical stresses can lead to bouts with the symptoms from lyase deficiency.
Treatment for Lyase Deficiency Disorder
1) Going long periods without eating food could amplify the symptoms of lyase deficiency so therefore someone with the disease should make sure they eat frequently and in good balance.
2) Eating foods high in carbohydrates and low in protein and fat may help prevent low blood sugar levels.
3) Taking L-Carnitine may aid in the body making cellular energy, which would help greatly when the body feels lethargic and dehydrated.
4) Even without the body's ability to produce leucine through the form of the enzyme lyase, most people may live a healthy lifestyle if they monitor their eating, exercising, and blood sugar levels carefully.
Examples of Lyases
A page with a list of Lyases can be found here