Carboxyl-containing metabolites (CCMs)

Carboxyl-containing metabolites (CCMs) represent a vast and diverse chemical class of endogenous molecules characterized by the presence of at least one carboxylic acid (-COOH) functional group. This group is estimated to comprise approximately 65% of the human endogenous metabolome and includes structurally diverse entities such as short-chain fatty acids (SCFAs), amino acids, bile acids, fatty acids, and tricarboxylic acid (TCA) cycle intermediates (Source: [5], [10]). Beyond their roles in central carbon metabolism and energy production, CCMs act as potent signaling molecules by binding to specialized receptors, notably the Free Fatty Acid Receptors (FFARs) and Hydroxycarboxylic Acid Receptors (HCARs), which regulate glucose homeostasis and inflammatory responses (Source: [1], [12]). Dysregulation of these metabolites is strongly linked to the pathophysiology of various conditions, including metabolic syndrome, chronic kidney disease, and several types of cancer, where they often serve as diagnostic or prognostic biomarkers (Source: [4], [5], [6]). Consequently, while not a single protein target, the pathways governed by these metabolites are major focal points for drug development in metabolic and inflammatory diseases.

Other names

Carboxylic acid-containing metabolitesCarboxyl metabolomeOrganic acidsCCMsCarboxylated small molecules

Carboxyl-containing metabolites act as endogenous ligands that activate specific G protein-coupled receptors (e.g., FFAR1, FFAR2, HCAR2), serve as substrates or modulators for metabolic enzymes, and function as agonists for nuclear receptors such as Peroxisome Proliferator-Activated Receptors (PPARs) and Farnesoid X Receptor (FXR).