Similarities Between Endocannabinoid Signaling in Animal Systems and N-Acylethanolamine Metabolism in Plants - Communication in Plants: Neuronal Aspects of Plant Life - page 211

A breakthrough in plant NAE research was accomplished by the re-
cent identification of a FAAH homolog (At5g64440) from the Arabidopsis
genome based upon the occurrence of the AS domain and conservation
of several key catalytic residues (Shrestha et al. 2003). The Arabidopsis
FAAH complementary DNA (cDNA) was predicted to encode a protein of
607 amino acids and the AS domain was nearly 60% identical to that of
the mammalian FAAH. Moreover, like mammalian FAAHs, the Arabidop-
sis FAAH protein contained a putative transmembrane domain near the
N-terminus and shared three domains of unknown function near the C-
terminus (Shrestha et al 2003). The recombinant Arabidopsis FAAH was
shown by biochemical analysis to hydrolyze a variety of plant NAEs and,
interestingly, had a higher affinity for anandamide. Furthermore, Arabidop-
sis FAAH activity was strongly inhibited by methylarchidonyl fluorophos-
phonate, an active-site-directed inhibitor of mammalian FAAH (Shrestra
et al. 2003). Thus, despite the low primary sequence similarity between
mammalian and Arabidopsis FAAH (just 18.5% identity over their entire
lengths), molecular and biochemical evidence indicate that the Arabidop-
sis At5g64440 gene encodes a functional NAE amidohydrolase. Hence, the
machinery for degradation of NAEs appears to be functionally conserved
between plants and animals (Fig. 14.2).
The cloning of mammalian FAAH paved the way for the generation of
animal models to characterize the role of this enzyme in endocannabinoid
signaling. As predicted, FAAH knockout mice exhibited a tenfold elevation
of anandamide and other NAEs when compared with wild-type mice. In
addition to exhibiting increased sensitivity to exogenously applied anan-
damide, FAAH knockout mice displayed a variety of physiological and be-
havioral abnormalities consistent with altered endocannabinoid signaling,
such as hypothermia and reduced response to pain (Cravatt et al. 2001).
Similar to the scenario in FAAH knockout mice, Arabidopsis seedlings
downregulating or overexpressing FAAH are altered in their sensitivity to
exogenously applied NAE. Preliminary results with FAAH transgenics are
beginning to indicate that the formation and degradation of NAE may be
important in mediating plant responses to the environment (Wang, Blan-
caflor and Chapman, unpublished data).
14.3.3
NAE Oxidation
NAE action in plants could be accomplished via the formation of oxylipins,
which are cyclic oxidation products derived from the catabolism of free
fatty acids (FFAs). In mammalian systems, oxidation products of polyun-
saturated NAEs, including eicosanoid ethanolamides, prostaglandins and