Phospholipase D catalyzes the hydrolysis of the phosphodiester bond of glycerophospholipids to generate phosphatidic acid and a free headgroup.
Phospholipase D (PLD) activity was first discovered in carrot extracts as a phospholipid-specific phosphodiesterase activity that hydrolysed phosphatidylcholine to yield phosphatidic acid (PA) and choline.
It is mainly specific for Phosphatidylcholine then Phosphatidylethanolamine.
Measures of Dispersion and Variability: Range, QD, AD and SD
Phospholipase D (PLD)
1. Phospholipase D: An Interfacial
Enzyme of Lipid Metabolism
SAKEEL AHMED (PhD Scholar)
Department of Pharmacology (NIPER, Mohali)
2. Phospholipase D catalyzes the hydrolysis of the phosphodiester bond of glycerophospholipids to generate
phosphatidic acid and a free headgroup.
Phospholipase D (PLD) activity was first discovered in carrot extracts as a phospholipid-specific
phosphodiesterase activity that hydrolysed phosphatidylcholine to yield phosphatidic acid (PA) and choline
Phospholipase D (PLD)
3. Structure of Phospholipase D
Catalytic domain is flanked by regulatory sequences. These include lipid-binding PX and
PH domains, as well as motifs that are unique to the PLD enzymes
The catalytic core of the eukaryotic PLD enzymes consists of four conserved regions (I–
IV).
Domains II and IV are particularly highly conserved and contain the invariant charged
motif, HxKxxxxD (HKD).
4. Mechanism of PLD Activity
Figure. Mechanisms of phospholipase D enzyme activities.
5. FIG. Schematic illustration of the two
extreme modes of interfacial catalysis on
vesicles. In the scooting mode (top) the
enzyme bound to the interface does not
dissociate during several thousand
turnover cycles. Under these conditions
the bound enzyme "sees“ only the
substrate and inhibitor at the interface to
which it is bound, and the excess vesicles
which do not contain enzyme are not
hydrolyzed, In the hopping mode (bottom)
the enzyme desorbs from the interface
after each or a few turnover cycles. Thus
excess vesicles are ultimately accessible
for hydrolysis.
7. Regulation of PLD
Fig. Regulation of PLD by cell surface receptors and intracellular signals through actions of intermediate
protein and lipid activators.
9. References
Selvy, P. E., Lavieri, R. R., Lindsley, C. W. & Brown, H. A. Phospholipase D : Enzymology
, Functionality , and Chemical Modulation. 6064–6119 (2011).
Majd, S., Yusko, E. C., Yang, J., Sept, D. & Mayer, M. A Model for the Interfacial
Kinetics of Phospholipase D Activity on Long- Chain Lipids. Biophysj 105, 146–153
(2013).
Mcdermott, M., Wakelam, M. J. O. & Morris, A. J. REVIEW / SYNTHÈSE Phospholipase
D 1 , 2. 253, 225–253 (2004).
Freyberg, Z., Siddhanta, A. & Shields, D. ‘ Slip , sliding away ’: phospholipase D and the
Golgi apparatus. (2003)
Editor's Notes
PH domain of PLD1 is required for localization to membranes in vitro. Phorbol esters, epidermal growth factor (EGF) and Platelet derived growth factor (PDGF).
Streptomyces chromofuscus PLD (scPLD). is the most well-characterized non-HKD PLD.22 scPLD exhibits both phosphodiesterase as well as phosphatase activities23and is proposed to be secreted by the bacteria to scavenge for phosphate in the microenvironment. scPLD activity is not dependent on the surface mole fraction of substrate within a lipid micelle or vesicle, and hence substrate presentation does not impact scPLD activity.
PKCα = Ca2+ Ca2þ-dependent isoform of PKC and PKCδ has been demonstrated to stimulate PLD activity. Additionally, members of the Rac- and Rho-GTPase family regulate PLD1 and PLD2 activities. GTP-bound form of ARF1 stimulates PLD1 catalytic activity more than 13-fold, whereas PLD2 is only stimulated 1.5-fold.
PKCα = Ca2+ Ca2þ-dependent isoform of PKC and PKCδ has been demonstrated to stimulate PLD activity. Additionally, members of the Rac- and Rho-GTPase family regulate PLD1 and PLD2 activities.