Mayer J M, Roy-De Vos M, Audergon C, Testa B, Etter J C
School of Pharmacy, University of Lausanne, Switzerland.
Int J Tissue React. 1994;16(2):59-72.
This review shows conclusively that profens can enter physiological pathways of lipid biochemistry. The first step in this interaction is the formation of an acyl-CoA thioester. These conjugates can lead to the incorporation of the xenobiotic acid into lipids. The resulting hybrid triglycerides have the potential to form long-lasting residues in adipose tissues and to be incorporated into membranes. Furthermore, the acyl-CoA conjugate may also alter lipid biochemistry by inhibiting lipid beta-oxidation either by interfering with the acyl-CoA synthetases or by modifying CoA levels. Thus, the acyl-CoA conjugates of profens intermediates in the inversion of inactive (R)-profens to active (S)-profens can be viewed as pivotal to bioactivation and to pathways of potential toxicity.
本综述确凿地表明，丙酸类药物可进入脂质生物化学的生理途径。这种相互作用的第一步是形成酰基辅酶A硫酯。这些共轭物可导致外源性酸掺入脂质中。由此产生的杂合甘油三酯有可能在脂肪组织中形成持久的残留物并掺入细胞膜。此外，酰基辅酶A共轭物还可能通过干扰酰基辅酶A合成酶或改变辅酶A水平来抑制脂质β-氧化，从而改变脂质生物化学。因此，丙酸类药物中间体的酰基辅酶A共轭物在无活性（R）-丙酸类药物转化为活性（S）-丙酸类药物的过程中，可被视为生物活化和潜在毒性途径的关键因素。
