Acyl-enzyme Intermediate

Definition

An acyl-enzyme intermediate is a transient covalent complex formed during enzymatic reactions, where the enzyme's active site temporarily binds to an acyl group from a substrate. This intermediate plays a crucial role in the catalytic mechanism of certain enzymes, particularly those involved in the hydrolysis or synthesis of ester, amide, or peptide bonds.

5 Must Know Facts For Your Next Test

1. The acyl-enzyme intermediate is a key step in the catalytic mechanism of enzymes that hydrolyze or synthesize ester, amide, or peptide bonds, such as proteases, lipases, and esterases.
2. The formation of the acyl-enzyme intermediate involves the nucleophilic attack of a catalytic serine, threonine, or cysteine residue on the carbonyl carbon of the substrate, resulting in the release of the leaving group.
3. The acyl-enzyme intermediate is stabilized by hydrogen bonding interactions with other active site residues, such as those in the catalytic triad of serine proteases.
4. The acyl-enzyme intermediate is subsequently hydrolyzed, releasing the product and regenerating the free enzyme for the next catalytic cycle.
5. The rate and efficiency of the acyl-enzyme intermediate formation and hydrolysis are critical factors that determine the overall catalytic activity and specificity of the enzyme.

Review Questions

• Describe the role of the acyl-enzyme intermediate in the catalytic mechanism of serine proteases.
  • In serine proteases, the acyl-enzyme intermediate is a key step in the hydrolysis of peptide bonds. The catalytic serine residue in the enzyme's active site performs a nucleophilic attack on the carbonyl carbon of the substrate, forming a covalent acyl-enzyme intermediate. This intermediate is stabilized by hydrogen bonding interactions with other active site residues, such as the histidine and aspartate residues of the catalytic triad. The acyl-enzyme intermediate is then hydrolyzed, releasing the product and regenerating the free enzyme for the next catalytic cycle.
• Explain how the formation and hydrolysis of the acyl-enzyme intermediate affects the overall catalytic activity and specificity of enzymes.
  • The rate and efficiency of the acyl-enzyme intermediate formation and hydrolysis are critical factors that determine the catalytic activity and specificity of enzymes. The stability and lifetime of the intermediate can influence the enzyme's turnover rate, as well as its ability to discriminate between different substrates. Enzymes with a more stable acyl-enzyme intermediate may have a higher catalytic efficiency but reduced substrate specificity, while those with a less stable intermediate may have lower overall activity but greater selectivity. The precise balance of these factors is what gives each enzyme its unique catalytic properties and allows it to perform its specialized function within the cell.
• Evaluate the significance of the acyl-enzyme intermediate in the context of the catabolism of triacylglycerols and the fate of glycerol.
  • The acyl-enzyme intermediate is a crucial step in the catabolism of triacylglycerols and the subsequent fate of glycerol. Lipases, the enzymes responsible for hydrolyzing the ester bonds in triacylglycerols, form an acyl-enzyme intermediate during their catalytic mechanism. This intermediate allows the lipase to efficiently cleave the ester bonds, releasing fatty acids and glycerol. The glycerol can then enter other metabolic pathways, such as gluconeogenesis or oxidation to produce energy, while the fatty acids can be further catabolized through $$\beta\text{-oxidation}$$ to generate ATP. The formation and hydrolysis of the acyl-enzyme intermediate in lipases is therefore a key step in the overall metabolism and utilization of triacylglycerols, the primary energy storage molecules in the body.

Related terms

Catalytic Triad: A set of three amino acid residues in the active site of certain enzymes, such as serine proteases, that work together to facilitate the formation of an acyl-enzyme intermediate during the reaction.

Serine Proteases: A class of enzymes that use a serine residue in their active site to form an acyl-enzyme intermediate during the hydrolysis of peptide bonds, as seen in digestive enzymes like trypsin and chymotrypsin.

Nucleophilic Attack: The process by which a nucleophilic group, such as the hydroxyl group of a serine residue, attacks the carbonyl carbon of a substrate to form the acyl-enzyme intermediate.