PPCS Human

Phosphopantothenoylcysteine Synthetase (PPCS) is an enzyme that plays a crucial role in the biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5). This enzyme is essential for various metabolic pathways in both prokaryotes and eukaryotes. The human recombinant form of PPCS is particularly significant for research and therapeutic applications.

The PPCS gene is located on chromosome 1 (1p34.2) in humans . It encodes a protein that is involved in the second step of the CoA biosynthesis pathway. The enzyme catalyzes the conversion of 4’-phosphopantothenate and L-cysteine to 4’-phosphopantothenoylcysteine, using ATP as a cosubstrate .

PPCS belongs to the family of ligases, specifically those forming carbon-nitrogen bonds as acid-D-amino-acid ligases (peptide synthases). The reaction it catalyzes is as follows :

$$\text{NTP} + (R)-4'-phosphopantothenate + \text{L-cysteine} \rightleftharpoons \text{NMP} + \text{diphosphate} + \text{N-[(R)-4'-phosphopantothenoyl]-L-cysteine}$$

In humans, PPCS prefers ATP over CTP as the nucleoside triphosphate (NTP) involved in the reaction .

The biosynthesis of CoA is a vital process for cellular metabolism. CoA is a cofactor that is involved in various biochemical reactions, including the synthesis and oxidation of fatty acids, and the metabolism of carbohydrates and amino acids. The role of PPCS in this pathway underscores its importance in maintaining cellular function and energy production .

Mutations in the PPCS gene have been associated with certain diseases, such as dilated cardiomyopathy (CMD2C) and familial isolated dilated cardiomyopathy . Understanding the function and regulation of PPCS can provide insights into these conditions and potentially lead to the development of targeted therapies.

Human recombinant PPCS is used in various research applications to study its structure, function, and role in metabolic pathways. It is also utilized in the development of assays and therapeutic interventions aimed at modulating CoA biosynthesis .