How Do Hydrolase Enzymes Work in Biological Processes?
Hydrolases are a type of enzyme that acts as a biochemical catalyst by breaking a chemical bond with water, resulting in the division of a larger molecule into smaller molecules. Esterase enzymes, such as lipases, phosphatases, glycosidases, peptidases, and nucleosidases, are examples of hydrolase enzymes.
Because of their degradative properties, hydrolase enzymes are important for the human body. Lipases help break down fats, lipoproteins, and other large molecules into smaller molecules like fatty acids and glycerol in lipids. Fatty acids and other small molecules are used as a source of energy and for synthesis.
A hydrolase is a type of enzyme that catalyses the hydrolysis of a chemical bond in biochemistry. A hydrolase, for example, is an enzyme that catalyses the following reaction:
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This article will study acid hydrolases, glycoside hydrolase and examples of hydrolases in detail.
Acid Hydrolases
Acid hydrolases are enzymes that function best when the pH is acidic. It's most commonly found in lysosomes, which have an acidic interior. Acid hydrolases include nucleases, proteases, glycosidases, lipases, phosphatases, sulfatases, and phospholipases, and they make up the lysosome's approximately 50 degradative enzymes.
Example of Hydrolases:
Nucleases
Lipase: for example lysosomal acid lipase.
Proteases
Glycoside hydrolase
Glycoside Hydrolase
Hydrolysis of glycosidic bonds in complex sugars is catalysed by glycoside hydrolases (also known as glycosidases or glycosyl hydrolases). They are extremely common enzymes that play a variety of roles in nature, including cellulose (cellulase), hemicellulose (hemicellulose), and starch (amylase) degradation, antibacterial protection strategies (e.g., lysozyme), pathogenesis mechanisms (e.g., viral neuraminidases), and normal cellular function (e.g., trimming mannosidases involved in N-linked glycoprotein biosynthesis). Glycosidases, together with glycosyltransferases, are the key enzymes involved in the synthesis and breakage of glycosidic bonds.
Epoxide Hydrolase
Epoxide hydrolases (EHs), also known as epoxide hydratases, are enzymes that metabolise compounds containing an epoxide residue, converting it to two hydroxyl residues through a dihydroxylation reaction, resulting in diol products. EH activity can be found in a variety of enzymes. The structurally linked isozymes microsomal epoxide hydrolase (mEH), soluble epoxide hydrolase (sEH, epoxide hydrolase 2, EH2, or cytoplasmic epoxide hydrolase), and the more recently discovered but not yet well described functionally, epoxide hydrolase 3 (EH3) and epoxide hydrolase 4 (EH4).
Lysosomal Hydrolase
Lysosomal lipase is a type of lipase that works inside the cell, in the lysosomes. Lysosomal lipase's primary role is to hydrolyze lipids including triglycerides and cholesterol. These fats are carried around and degraded into free fatty acids. Lysosomal lipases work best in an acidic pH range, which is compatible with the lysosomal lumen environment. Only the lipids present in organelle membranes and extracellular lipids were thought to be hydrolyzed by these enzymes.
Serine Hydrolase
Serine hydrolases are one of the largest known enzyme groups, accounting for around 200 enzymes or 1% of the human proteome's genes. The presence of a nucleophilic serine in the active site, which is used for substrate hydrolysis, is a distinguishing feature of these enzymes. Via this serine, catalysis begins with the formation of an acyl-enzyme intermediate, followed by saponification of the intermediate by water/hydroxide and regeneration of the enzyme. The nucleophilic serine of these hydrolases, unlike other non-catalytic serines, is normally activated by a proton relay involving a catalytic triad consisting of the serine, an acidic residue (e.g. aspartate or glutamate), and a simple residue (usually histidine), though there are variations on this mechanism.
Cholesterol Ester Hydrolase
A sterol esterase is an enzyme that catalyses the chemical reaction in enzymology.
Sterol Ester + H2O sterol + fatty acid
Thus, sterol ester and H2O are the enzyme's two substrates, while sterol and fatty acid are the enzyme's two products.
Bile Salt Hydrolase
Intestinal bacteria manufacture bile salt hydrolase (BSH), which catalyses the deconjugation of glyco- and Tauro-conjugated bile acids by hydrolyzing the amide bond and releasing free bile acids (e.g. cholic acid and chenodeoxycholic acid) and amino acids (glycine and taurine).
Soluble Epoxide Hydrolase
The EPHX2 gene encodes a bifunctional enzyme known as soluble epoxide hydrolase (sEH). The epoxide hydrolase family includes sEH. This enzyme binds to various epoxides and transforms them to the corresponding diols in the cytosol and peroxisomes. This protein also has lipid-phosphate phosphatase activity in another area. Familial hypercholesterolemia has been linked to mutations in the EPHX2 gene.
Alpha Beta Hydrolase
The alpha/beta hydrolase superfamily is a group of hydrolytic enzymes with a similar fold but different phylogenetic origins and catalytic functions. Each enzyme consists of an alpha/beta-sheet (rather than a barrel) with 8 beta strands linked by 6 alpha-helices at its centre. The enzymes are thought to have diverged from a common ancestor, maintaining no apparent sequence similarity but retaining the catalytic residues' structure. All of them have a catalytic triad, the components of which are carried on loops, the fold's most well-preserved structural features.
Nudix Hydrolase
Nudix hydrolases are a group of hydrolytic enzymes that can cleave nucleoside diphosphates linked to any moiety, hence their name. Nucleoside monophosphate (NMP) and X-P are the products of the reaction. With varying degrees of substrate specificity, nudix enzymes hydrolyze a broad variety of organic pyrophosphates, including nucleoside bi- and triphosphates, dinucleoside and diphosphoinositol polyphosphates, nucleotide sugars, and RNA caps. The Nudix superfamily of enzymes can be present in eukaryotes, bacteria, and archaea, among other species.
Bleomycin Hydrolase
Bleomycin hydrolase (BMH) is a cytoplasmic cysteine peptidase with a long evolutionary history. Hydrolysis of the reactive electrophile homocysteine thiolactone is its biological function. Another of its functions is metabolic inactivation of the glycopeptide bleomycin (BLM), which is an important component of cancer treatment regimens. The protein has the cysteine protease papain superfamily's characteristic active site residues.
Did You Know?
Acetylcholinesterase is one of the most common hydrolases (cholinesterase). Acetylcholine is a powerful neurotransmitter involved in voluntary muscle contraction. Nerve impulses pass through neurons to the synaptic cleft, where acetylcholine stored in vesicles is released, bringing the impulse through the synapse and propagating the nerve impulse to the postsynaptic neuron. After the nerve impulse has passed, cholinesterase, which hydrolyzes acetylcholine to choline and acetic acid, must interrupt the activity of the neurotransmitter molecules. Some harmful toxins, such as Clostridium botulinum exotoxin and saxitoxin, interact with cholinesterase, and many nerve agents, such as tabun and sarin, work by binding to cholinesterase.
FAQs on Hydrolase Enzymes: Definition, Types, and Key Roles
1. What are hydrolase enzymes and what is their primary role in biochemistry?
Hydrolase enzymes are a major class of enzymes (EC 3) that act as biochemical catalysts for hydrolysis reactions. Their primary role is to use a water molecule to break a chemical bond, effectively splitting a larger, more complex molecule into smaller, simpler ones. This process is fundamental to digestion and cellular metabolism.
2. What are the main types of hydrolase enzymes based on the bonds they target?
Hydrolase enzymes are classified based on the specific type of chemical bond they break. The main types include:
- Esterases: These enzymes break ester bonds, which are found in lipids. A key example is lipase.
- Proteases (or Peptidases): These break the peptide bonds that link amino acids together in proteins. Examples include pepsin and trypsin.
- Glycosidases: These target glycosidic bonds in carbohydrates, breaking down starches and sugars. Amylase is a well-known example.
- Nucleases: These are responsible for breaking the phosphodiester bonds within nucleic acids like DNA and RNA.
3. Can you provide some examples of common hydrolase enzymes and their functions?
Some of the most common hydrolase enzymes include lipase, which digests fats (triglycerides) into fatty acids and glycerol; amylase, found in saliva and the pancreas, which breaks down starch into simpler sugars; and sucrase, which splits the sugar sucrose into glucose and fructose. All these are vital for nutrient absorption.
4. Where are hydrolase enzymes typically found in the human body?
Hydrolase enzymes are prevalent throughout the human body, especially in the digestive system. They are secreted in saliva, stomach acid (as pepsin), pancreatic juice (as trypsin and lipase), and the small intestine. Additionally, they are found within cellular organelles called lysosomes, where they break down cellular waste and foreign materials.
5. What kind of chemical reaction is catalysed by a hydrolase enzyme?
A hydrolase enzyme catalyses a hydrolysis reaction. In this reaction, one molecule of water is consumed to break a specific covalent bond in the substrate molecule. For a substrate represented as A–B, the general reaction is: A–B + H₂O → A–OH + B–H. The water molecule is split, with -OH attaching to one part and -H to the other.
6. How are hydrolases fundamentally different from lyases?
The fundamental difference lies in their mechanism for breaking bonds. Hydrolases use a molecule of water to cleave a bond (hydrolysis). In contrast, lyases break bonds through an elimination reaction, which does not involve water. This lyase-catalysed reaction often results in the formation of a new double bond or a ring structure in the product molecule.
7. Can a hydrolase enzyme perform its function without the presence of water?
No, a hydrolase enzyme cannot perform its catalytic function without water. The term 'hydrolase' itself points to its mechanism—hydrolysis, which is the chemical breakdown of a compound due to reaction with water. The water molecule is a direct reactant in the process, making it essential for the enzyme's activity.
8. Why are the hydrolase enzymes found in lysosomes known as 'acid hydrolases'?
They are called acid hydrolases because they are designed to function optimally in the highly acidic environment of the lysosome, which has a pH of approximately 4.5 to 5.0. This is a crucial safety feature; if a lysosome were to leak its contents into the cell's cytoplasm (which has a neutral pH of ~7.2), these enzymes would become largely inactive, preventing them from damaging the cell itself.
9. How do common digestive enzymes like pepsin and lipase perfectly exemplify the role of hydrolases?
Pepsin and lipase are classic examples of hydrolases because their primary job is to break down large food molecules using water.
- Pepsin, a protease in the stomach, uses water to break the peptide bonds in proteins, converting them into smaller polypeptides.
- Lipase, from the pancreas, uses water to break the ester bonds in fats (triglycerides), splitting them into absorbable fatty acids and glycerol.
Both enzymes facilitate digestion through hydrolysis.
