Fig. 5: Isoprene production pathway with IDI2 activity in human skeletal-myocyte.
From: Origin of breath isoprene in humans is revealed via multi-omic investigations
The pathway is based on the results of this study. The pathway depicts the potential contributions of myocellular organelles, e.g., sarcoplasm, sarcoplasmic reticulum (SR), mitochondria and most importantly the peroxisomes. Human IDI2 is only and highly expressed within the myocellular peroxisomes. Peroxisomes are metabolic organelle—mainly responsible for lipolysis. Here, acetyl-CoA is produced via beta-oxidation of fatty acids within peroxisomes. Acetyl-CoA is then channeled towards farnesyl-PP (FPP) production. One step before the FPP generation, isopentyl-PP (IPP) is converted into its active isoform dimethylallyl-PP (DMAPP) by the IDI2 activity. IDI2 does not convert DMAPP back to IPP. In human, DMAPP is the only source of isoprene. Unlike plants, humans lack isoprene synthase and its enzyme homologue. Thus, IDI2 determines human isoprene production in skeletal-myocytes. Farnesyl-PP exits peroxisomes and enters other organelles to execute in other metabolic pathways, e.g., cholesterol metabolism in the SR.
