Lyases

For medical students2 min readUpdated 2026-10-10

Lyases are enzymes that catalyze the non-hydrolytic cleavage of various chemical groups from substrates, as well as the addition of molecules across double bonds. The main feature of these biocatalysts is that bond cleavage occurs without the participation of water as a cleaving agent.

MechanismNon-hydrolytic cleavage of groups

GroupsCleavage of $CO_2$, $H_2O$, $NH_2$, $SH_2$, etc.

BondsAddition of molecules across double bonds

CoenzymePyridoxal phosphate (PLP) for decarboxylases

Principles of Lyase Action

These enzymes perform two key, yet functionally opposite tasks. First, they can cleave specific groups ($CO_2$, $H_2O$, $NH_2$, $SH_2$) from substrate molecules. The most important condition is that this occurs via a non-hydrolytic pathway, meaning water does not act as "scissors" (a cleaving agent).

Second, lyases can catalyze addition reactions. Most commonly, this involves the addition of a small molecule (such as water) directly across a double bond of the substrate molecule, leading to a change in its chemical structure.

Decarboxylation Reactions

A classic example of group cleavage is decarboxylation. During this reaction, enzymes remove a carboxyl group (-COOH).

Let us examine this process using a specific example:

Substrate: Glutamic acid (also known as glutamate).
Enzyme: Glutamate decarboxylase.
Coenzyme: Pyridoxal phosphate (PLP).
Reaction products: $\gamma$-aminobutyric acid (GABA) is formed, and carbon dioxide ($CO_2$) is released.

Mechanism: The carboxyl group is removed from the $\alpha$-position of glutamic acid. This is how a new molecule is formed through the elimination of $CO_2$.

Water Addition (Hydratase) Reactions

The second major type of lyase reaction is addition. An example of a hydratase reaction is the interaction of a substrate with a water molecule.

Substrate: Fumarate.
Enzyme: Fumarate hydratase (or fumarase).
Reaction equation: `Fumarate + H₂O` $\rightleftarrows$ `Malate`.

Mechanism: Water adds strictly across the double bond of the fumarate molecule. As a result, the double-bond region ($CH=CH$) becomes saturated and converts into a single bond with a hydroxyl group ($CH_2-CH(OH)$), forming malate. This reaction is reversible.

Mnemonic

To remember the core concept, imagine lyases as "dry scissors" (cutting off groups without water) or "glue for double bonds" (adding molecules to replace a double bond).

Frequently asked questions

Which enzyme class do lyases belong to in the international classification?

According to the international enzyme classification, lyases belong to the fourth class of enzymes. All known enzymes are systematically divided into six major groups based on the type of reaction catalyzed, with lyases assigned the fourth ordinal number.

How do lyases fundamentally differ from hydrolases?

The fundamental difference lies in the mechanism of chemical bond cleavage and the involvement of water molecules in the catalysis process.

Feature	Lyases	Hydrolases
Cleavage mechanism	Non-hydrolytic bond cleavage	Bond cleavage involving water
Reaction type	Elimination of groups without water or addition across double bonds	Transfer of groups to water

What subclasses of enzymes belong to lyases besides decarboxylases and hydratases?

Aside from decarboxylases and hydratases, important subclasses of lyases include:

C-C lyases
C-O lyases
C-N lyases
C-S lyases

Additionally, in the enzyme commission classification, class 4 is designated as lyases (synthases).

In which metabolic pathway does fumarate hydratase operate?

Fumarate hydratase (fumarase) functions in the aspartate-argininosuccinate shunt and the tricarboxylic acid (TCA) cycle, where it catalyzes the hydration of fumarate to form malate.

What is the biological role of GABA formed during glutamate decarboxylation?

GABA ($\gamma$-aminobutyric acid), formed by the decarboxylation of glutamic acid, serves as the major inhibitory neurotransmitter in the central nervous system.

Do lyases use water to cleave bonds?

No. Lyases cleave chemical groups ($CO_2$, $NH_2$, etc.) via a non-hydrolytic pathway, meaning water does not participate in the reaction as a cleaving agent.

Which group is removed during glutamate decarboxylation?

During the action of glutamate decarboxylase, the carboxyl group (-COOH) is cleaved from the $\alpha$-position of glutamic acid.

How does bond structure change during the action of fumarase?

Fumarase adds water across the double bond of fumarate ($CH=CH$). The double bond is broken, and $CH_2-CH(OH)$ is formed—the malate molecule.

Go deeper

Role and functions of $\gamma$-aminobutyric acid (GABA)
Structure and function of the coenzyme pyridoxal phosphate (PLP)
Significance of the fumarate-to-malate conversion reaction
Cleavage of other groups: ammonia ($NH_2$) and hydrogen sulfide ($SH_2$)