University:
York University
Course:
CHEM 2021 | Introductory Organic Chemistry II
Academic year:

2023
Views:

437

Pages:

5
Author:

Niklas

PLP as a Coenzyme: Structure: PLP is a derivative of vitamin B6 and plays a crucial role in many enzymatic reactions. Functions: It is involved in various reactions, including amino acid transamination, racemization, decarboxylation, and synthesis of small molecules. How PLP Attaches to an Enzyme: Condensation: PLP attaches to an enzyme through a condensation reaction between the aldehyde group of PLP and a lysine residue on the enzyme. This forms a Schiff base linkage. Mechanism of PLP-Catalyzed Reactions: The image depicts a general mechanism for PLP-dependent reactions. It involves the following steps: Substrate Binding: The amino acid substrate binds to PLP through a Schiff base linkage. Formation of a Quinonoid Intermediate: The amino acid side chain undergoes a series of proton transfers and electron rearrangements, leading to the formation of a quinonoid intermediate. Product Formation: The quinonoid intermediate can undergo various reactions, such as transamination, decarboxylation, or racemization, depending on the specific enzyme and reaction conditions. The final product is released, and PLP is regenerated for another catalytic cycle. I. AA Decarboxylase Example Reactions: The diagram shows two specific examples of amino acid decarboxylation reactions catalyzed by PLP-dependent enzymes: L-DOPA to Dopamine: L-DOPA (L-3,4-dihydroxyphenylalanine) is decarboxylated to form dopamine. Histidine to Histamine: Histidine is decarboxylated to form histamine. II. Mechanism of AA Decarboxylation The mechanism involves the following steps: Substrate Binding: The amino acid substrate binds to the PLP cofactor through a Schiff base linkage. Transamination: The α-amino group of the amino acid is transferred to PLP, forming a new Schiff base intermediate. Decarboxylation: The α-carboxyl group of the amino acid is eliminated as CO2, resulting in a carbanion intermediate. Protonation: A proton is transferred from the PLP cofactor to the carbanion, forming a new carbon-hydrogen bond. Product Release: The product (amine) is released from the enzyme, and PLP is regenerated for the next catalytic cycle.2. PLP - Transamination: Overview: The diagram shows a general mechanism for transamination reactions catalyzed by PLP-dependent enzymes. In this reaction, an amino group from an amino acid is transferred to an α-keto acid, resulting in the formation of a new amino acid and a new α-keto acid. Example Reaction: The diagram shows a specific example of transamination involving glutamic acid and pyruvate. Glutamic acid donates its amino group to pyruvate, forming α-ketoglutarate and alanine. Mechanism: Substrate Binding: The amino acid substrate binds to the PLP cofactor through a Schiff base linkage. Transamination: The α-amino group of the amino acid is transferred to PLP, forming a new Schiff base intermediate. Proton Transfer: A proton is transferred from the PLP cofactor to the α-carbon of the amino acid, forming a carbanion intermediate. Keto Acid Formation: The carbanion intermediate attacks the carbonyl carbon of the α-keto acid, resulting in the formation of a new Schiff base intermediate. Product Release: The product amino acid is released from the enzyme, and PLP is regenerated for the next catalytic cycle.