Long‐chain acyl‐coenzyme a synthetase in rat brain myelin

Abstract

Long-chain acyl-CoA synthetase (EC 6.2.1.3), an enzyme(s) that activates fatty acids prior to incorporation into phospholipids and other substances, has been detected in highly purified myelin from rat brain stem. The high levels relative to microsomes (11% and 15% for oleate and arachidonate, respectively) tended to preclude contamination by the latter membrane as the source of activity. Additional evidence came from sequential purification and mixing experiments. Km values were not appreciably different for the two substrates with the two membranes, but Vmax values were approximately 2-4-fold greater for arachidonate in both membranes. Triton X-100 increased activity somewhat in myelin but not in microsomes; with arachidonate as substrate it reduced activity in the latter. Heat inactivation studies and pH profiles suggested the presence of two different enzymes, as previously shown for other tissues.

TNFα downregulates PPARδ expression in oligodendrocyte progenitor cells: Implications for demyelinating diseases

“…Several functions have been proposed for ACS2 in brain: maturation of neurons, which involves lipid biosynthesis and turnover; signal transduction pathways involving acyl-CoA esters (Faergeman and Knudsen, 1997) such as the stimulation of Ca 2ϩ release from intracellular compartments (Fulceri et al, 1993(Fulceri et al, , 1994Dumonteil et al, 1994) and stimulation of ion channels (Kakar et al, 1987;Larsson et al, 1996); and activation of fatty acids (Whali et al, 1995). ACS activity has been found also in myelin sheets (Vaswani and Ledeen, 1987) and even if the form involved is not yet determined, it may be involved in lipid turnover; acylation of myelin proteins (Campagnoni and Macklin, 1988) such as PLP, one of the major components of mature myelin responsible for the stabilization of the myelin sheets. PLP has been postulated to play a critical role in the early differentiation of OLs.…”

“…Moreover, PPAR␦ has been demonstrated to regulate acyl-CoA synthetase 2 (ACS2) expression in brain (Basu-Modak et al, 1999). ACS is particularly important in activating fatty acids that need to be transformed into acyl-CoA derivatives for their metabolism and its activity has been reported also in myelin (Vaswani and Ledeen, 1987). Acylation is a common posttranslational modification of myelin proteins (Campagnoni and Macklin, 1988) such as proteolipid protein (PLP).…”

Peroxisome Proliferator-activated Receptor β Regulates Acyl-CoA Synthetase 2 in Reaggregated Rat Brain Cell Cultures

“…55), the bound fatty acids of which are turned over very rapidly (3). ACS activity has been reported in myelin (21), but the type involved not yet determined. It will be the aim of future work to investigate whether and how ACS2 is involved in the processes described above.…”

“…Brain lipids serve primarily in modifying the fluidity, structure, and functions of the membranes, and both anabolic and catabolic pathways of lipid metabolism are important in brain development (18,19). Fatty acids need to be activated to their acyl-CoA by acyl-CoA synthetases (ACSs), the activities of which have been found in the brain (20,21). Moreover, ACS1, ACS2, and ACS3 mRNAs have been analyzed in the postnatal rat brain, and the levels of ACS2 and ACS3 vary during its development (22).…”

Growth, Adipose, Brain, and Skin Alterations Resulting from Targeted Disruption of the Mouse Peroxisome Proliferator-Activated Receptor β(δ)

“…5). Since two ACS are expressed in the developing rodent brain and have important roles in fatty acid utilization (15,43,50) and since recent data suggest that PPAR␤ regulates ACS-2 (6), expression of the mRNAs for these enzymes were also analyzed. As shown in Fig.…”