Synthesis of fatty acid ethyl esters in mammalian tissues after ethanol exposure: a systematic review of the literature

Abstract

The ability to undergo non-oxidative metabolism from ethanol to fatty acid ethyl esters (FAEEs) varies greatly among tissues and organs. To gain a greater understanding of non-oxidative ethanol metabolism to FAEE, we aimed to collect all published data on FAEE synthesis in mammalian organs and tissues to identify all tissues, organs, and enzymes that are known to, or likely possess FAEE-synthetic activity. A systematic search for relevant papers was performed and two independent reviewers examined potentially relevant abstracts (articles on FAEEs that pertain to ethanol exposure) to determine whether they met the inclusion criteria. Information on FAEE synthesis was retrieved from papers meeting the inclusion/exclusion criteria and summarized by organ/tissue/matrix examined. The systematic search through four databases yielded 78 articles that investigated FAEE synthesis by tissues, tissue fractions and cell lines, and 29 articles that attempted to purify and/or characterize the enzymes involved in FAEE synthesis. Two enzyme activities have been studied: FAEE synthase (FAEES, which conjugates ethanol and free fatty acid) and acyl-CoA: ethanol O-acyltransferase (AEAT, which conjugates ethanol and fatty acyl-CoA). Both activities are expressed by a variety of different enzymes. FAEES activity is the most widely studied and has been purified from several tissues and shown to be associated with several well-known enzymes, while the identity of enzymes possessing AEAT activity remains unknown. The organs and tissues that have been shown to synthesize FAEEs are discussed, with special emphasis on the studies that attempted to elucidate the enzymology of FAEE synthesis in those tissues.

A Mechanistic Review of Cell Death in Alcohol‐Induced Liver Injury

“…In the first pathway, ethanol interacts with fatty acid and generates fatty acid ethyl ester (FAEE) through FAEE synthase (Zelner et al, 2013). Increasing evidence shows that FAEE exacerbates alcohol-induced injury in various tissues including liver (Wu et al, 2006), pancreas (Wu et al, 2008, Werner et al, 2002), and heart (Beckemeier and Bora, 1998, Wu et al, 2008, Wu et al, 2006).…”

Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

“…Additionally, a minimal amount of ethanol can also be metabolized via two nonoxidative pathways. In the first pathway, ethanol interacts with fatty acid and generates fatty acid ethyl ester (FAEE), which is catalyzed by FAEE synthase in many tissues and organs [22]. FAEE was thought to have minor effect and mainly considered as a diagnostic marker but accumulated evidence shows that FAEE exacerbates injury after ethanol exposure especially in pancreas [23, 24], liver [25], and heart [23, 25, 26] and is facilitated by ADH deficiency [27].…”

Fatty Acid Ethyl Esters Disrupt Neonatal Alveolar Macrophage Mitochondria and Derange Cellular Functioning

“…Neonatal control lungs demonstrated measurable FAEEs as have been demonstrated in control samples from other animal models including mice (Bearer et al., 1992), ewes (Zelner et al., 2013), as well as meconium from control guinea pigs (Brien et al., 2006). Ethyl linoleate was significantly increased in the neonatal lung after in utero ethanol exposure (Table2, p  ≤ 0.05).…”

“…Although FAEEs in meconium are most notably known for their use as a biomarker of in utero alcohol exposure in the newborn (Bearer et al., 1992, 2005; Best and Laposata, 2003; Chan et al., 2004a,b; Gareri et al., 2009; Ostrea et al., 2006), FAEEs have been demonstrated to accumulate in a variety of alcohol-exposed fetal tissues (Bearer et al., 1992; Zelner et al., 2013). With exposure to alcohol, synthesis of FAEEs can occur either from the conjugation of ethanol and free fatty acid via FAEE synthase, or from the conjugation of ethanol and fatty acyl-CoA via acyl-CoA: ethanol O-acyltransferase.…”

“…With exposure to alcohol, synthesis of FAEEs can occur either from the conjugation of ethanol and free fatty acid via FAEE synthase, or from the conjugation of ethanol and fatty acyl-CoA via acyl-CoA: ethanol O-acyltransferase. Activity of these enzymes has been demonstrated in multiple fetal organs in animal models of ethanol exposure, including the lung (Manautou et al., 1992; Zelner et al., 2013). To advance our understanding of in utero ethanol's effects on neonatal AM functioning, the current study tested our hypotheses that FAEEs accumulate in ethanol-exposed neonatal lung and directly contribute to AM dysfunction via MT injury.…”