Biochemistry & Molecular Biology Journal Open Access

Keywords

Alpha/Beta; Hydrolase; Lipid; Acyltransferase; Lipase; Arabidopsis

Description

The ABHD family of proteins is rapidly becoming as structurally related enzymes with various biochemical functions in both synthesis and degradation. The proteins have a conserved lipase (GXSXG) and acyltransferase (HXXXXD) motifs, which suggests that they may have a role in lipid biosynthesis and turnover [1]. In recent years, the mammalian ABHD proteins are likely to have regulatory functions of lipid metabolism and signal transduction. To date, eighteen human ABHD hydrolases and their expression in various tissues have been reported, but most need to be characterized [2]. Mutations in ABHD5/CGI58 cause Chanarin– Dorfman syndrome, an autosomal recessive disorder in humans [3- 5]. Human CGI-58 has lysophosphatidic acid (LPA) acyltransferase [6] and lysophosphatidyl glycerol acyltransferase [7] activities. In various cancers, high levels of ABHD11 mRNA transcripts have been reported, but the role of this enzyme in cancer metabolism is not known. ABHD11 has been identified as a possible biomarker for lung carcinoma [8]. In vivo metabolite profiling disclosed that human ABHD3 overexpressing cells exhibited elevated levels of phospholipase activity [9]. In a similar study, ABHD6 was shown to have an enzymatic activity that hydrolyzed both monoacylglycerol (MAG) and lysophospholipid [10]. In a rodent model, ABHD12 was reported to be a major lysophosphatidyl serine and MAG lipase [11]. Similarly, ABHD16A was shown to hydrolyze phosphatidylserine in mammalian systems. Disruption of these two enzymes showed altered phospholipid and lysophospholipid levels and caused neuro-immunological disorders in mice [12]. From the above research, it is clear that ABHD proteins in human are playing the vital roles in with respect to lipid metabolism and various disease conditions.

Unlike human ABHD proteins, in plants, very few studies demonstrated the biochemical and physiological functions of these ABHD family proteins. Recombinant Arabidopsis CGI58 was shown to possess LPA acyltransferase activity [13]. Accumulation of nonpolar lipids in the leaves of Arabidopsis CGI58 mutants was also demonstrated [14]. Our recent research on ABHD11 of Arabidopsis revealed that the heterologously overexpressed ABHD11 had the ability to hydrolyze lysolipids, phospholipids and to some extent monoacylglycerol. The mutant ABHD11 altered the plant growth and the expression levels of various chloroplast lipid biosynthetic genes and eventually increased the galactolipids in leaves [15].

Various attempts are upcoming to increase the oil content in plant seeds. Our studies on ABHD family proteins revealed that abolishing the enzyme activity influences the lipid biosynthesis more towards leaf lipids such as galactolipids and less towards storage lipids. Galactolipids are the abundant lipid found in leaves and are vital for photosynthesis. Hence, in depth knowledge is required on plant ABHD proteins to disclose its physiological roles with respect to lipid metabolism.

Acknowledgement

This study was supported by Council of Scientific and Industrial Research (CSIR), New Delhi.

References

1. Lord CC, Thomas G, Brown JM (2013) Mammalian alpha beta hydrolase domain(ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism. BiochimBiophysActa1831:792-802.
2. Lord CC, Betters JL, Ivanova PT, Milne SB, Myers DS, et al. (2012)CGI-58/ABHD5-derived signaling lipids regulate systemic inflammation and insulin action. Diabetes 61: 355-363.
3. Rozenszajn L, Klajman A, YaffeD,Efrati P (1966) Jordans’ anomaly in white blood cells:A case report. Blood28: 258-265.
4. Dorfman ML, Hershko C, Eisenberg S, Sagher F (1974) Ichthyosiformdermatosis with systemic lipidosis. Arch Dermatol 110:261-266.
5. Chanarin I, Patel A, Slavin G, Wills EJ, Andrews TM, et al. (1975) Neutral lipid storage disease: A new disorder of lipid metabolism. Br Med J 1:553-555.
6. Ghosh AK, Ramakrishnan G, Chandramohan C, Rajasekharan R (2008a) CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid. J BiolChem 283:24525-24533.
7. Zhang J, Xu D, Nie J, Han R, Zhai Y, et al. (2014) Comparative gene identification-58 (CGI-58) promotes autophagy as a putative lysophosphatidylglycerolacyltransferase. J BiolChem 289: 33044-33053.
8. Wiedl T, Arni S, Roschitzki B, Grossmann J, Collaud S, et al. (2011) Activity-based proteomics: identification ofABHD11 and ESD activities as potential biomarkers for human lung adenocarcinoma. J Proteomics 74:1889-1894.
9. Long JZ, Cisar JS, Milliken D, Niessen S, Wang C, et al. (2011) Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids. Nat ChemBiol 7: 763-765.
10. Thomas GT, Betters JL, Lord CC, Brown AL, Marshall S, et al. (2013) The serine hydrolase ABHD6 is a critical regulator of the metabolic syndrome. Cell Rep 5:508-520.
11. Blankman JL, Long JZ, Trauger SA, Siuzdak G, Cravatt BF (2013) ABHD12controls brain lysophosphatidylserine pathways that are deregulated in a murine model of the neurodegenerative disease PHARC. ProcNatlAcadSci110:1500-1505.
12. Kamat SS, Camara K, Parsons WH, Chen DH, Dix MM, et al. (2015) Immunomodulatorylysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nat ChemBiol 11:164-171.
13. Ghosh AK, Neha C, Rajakumari S, Daum G, Rajasekharan R (2009)AT4G24160, a soluble acyl-coenzyme A-dependent lysophosphatidic acid acyltransferase. Plant Physiol 151:869-881.
14. James CN, Horn PJ, Case CR, Gidda SK, Zhang D, et al. (2010) Disruption of the Arabidopsis CGI-58homologue produces Chanarin-Dorfman-like lipid droplet accumulation in plants. ProcNatlAcadSci USA 107:17833-17838.
15. Vijayakumar A, Panneerselvam V, Vijayakumar AK, Rajasekharan R(2016) The Arabidopsis ABHD11 mutant accumulates polar lipids in leaves as a consequence of absent acylhydrolase activity. Plant Physiol 170:180-193.