and its stimulus is transferred to each corresponding functional protein through G
protein. A series of cellular signaling process is affected by structure and physical
property of lipid membrane. Major components of membrane, phospholipids are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol,
phosphatidic acid. In metabolic pathway of biosynthesis for phospholipids, phosphatidic acid is synthesized from fatty acyl-CoA and glycerol phosphate, and it is
converted to diacylglycerol, a start molecule for synthesis of phospholipid. Synthetic
reaction is generally chemical reaction with positive change of standard free energy,
and nucleotide triphosphate such as ATP, CTP, GTP and UTP is required to couple
with synthetic reaction for supplying energy by its hydrolysis of negative change of
standard free energy. And nucleotide triphosphate is also used for activation of
binding site. In one pathway of phospholipid biosynthesis, diacylglycerol (DG) is
activated by CTP and CDP-diacylglycerol is generated. In another pathway, polar
base is activated by CTP to generate CDP-polar base and then it binds to
diacylglycerol to generate CDP-diacylglycerol. Phosphatidylinositol (PI) is synthesized in former pathway. Phosphatidylcholine (PC) and phosphatidylethanolamine
(PE) are synthesized in latter pathway. Phosphatidylserine (PS) is synthesized from
PE by exchange reaction with minor change of standard free energy. These biosynthetic pathways are shown in Fig. 6.3). On the other hand, hydrolysis of phospholipids is mediated by phospholipases such as phospholipase A, phospholipase C and
phospholipase D. These chemical reactions proceed with negative change of standard free energy. These enzymes are activated when a cell receives stimulus, and
rapid conversion of lipid is observed. Phospholipase A releases fatty acid from
phospholipid and the released arachidonic acid becomes substrate for generation
of prostaglandin, leukotriene, and thromboxane and so on. And these molecules
regulate functions of cell. Phospholipase C generates diacylglycerol from
phosphatidylinositol as substrate, and the diacylglycerol as second messenger activates protein kinase C. And phospholipase D generates phosphatidic acid from
mainly phosphatidylcholine as substrate, and the phosphatidic acid induces proliferation of cell. Regulation of physiological function of cell is performed by transfer
of phosphate moiety of ATP to protein, i.e. phosphorylation of protein. Energy of
ATP is used in phosphorylation process. For example, some species of protein
kinases are activated sequentially in cycle of cell division, and proliferation and
differentiation of cell are also regulated by protein kinase. And malfunction of this
mechanism is supposed to induce cancer cell from study of oncogene. Malfunction
of protein kinase C is a candidate of canceration of cell. Phosphatidylserine, calcium
ion and diacylglycerol are required for activation of protein kinase C [16]. Protein
kinase C in cytoplasm was bound to plasma membrane when cell received a specific
stimulus [17], and calcium ion was required for binding of protein kinase C
[18]. Diacylglycerol of neutral lipid generated from negatively charged
phosphatidylinositol was supposed to promote calcium ion-induced phase separation
of phosphatidylserine in signaling of cell because of the phase separation in signaling -mimicking artificial membrane system [19]. Stimulus received by receptor
raised concentration of calcium ion from 0.2 μM to 0.6 μM in liver cell [20], and
promotion of phase separation of phosphatidylserine by diacylglycerol was also
6.4 Conversion of Membrane Lipid with Receiving Stimulus and Functions of a Cell
85
protein. A series of cellular signaling process is affected by structure and physical
property of lipid membrane. Major components of membrane, phospholipids are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol,
phosphatidic acid. In metabolic pathway of biosynthesis for phospholipids, phosphatidic acid is synthesized from fatty acyl-CoA and glycerol phosphate, and it is
converted to diacylglycerol, a start molecule for synthesis of phospholipid. Synthetic
reaction is generally chemical reaction with positive change of standard free energy,
and nucleotide triphosphate such as ATP, CTP, GTP and UTP is required to couple
with synthetic reaction for supplying energy by its hydrolysis of negative change of
standard free energy. And nucleotide triphosphate is also used for activation of
binding site. In one pathway of phospholipid biosynthesis, diacylglycerol (DG) is
activated by CTP and CDP-diacylglycerol is generated. In another pathway, polar
base is activated by CTP to generate CDP-polar base and then it binds to
diacylglycerol to generate CDP-diacylglycerol. Phosphatidylinositol (PI) is synthesized in former pathway. Phosphatidylcholine (PC) and phosphatidylethanolamine
(PE) are synthesized in latter pathway. Phosphatidylserine (PS) is synthesized from
PE by exchange reaction with minor change of standard free energy. These biosynthetic pathways are shown in Fig. 6.3). On the other hand, hydrolysis of phospholipids is mediated by phospholipases such as phospholipase A, phospholipase C and
phospholipase D. These chemical reactions proceed with negative change of standard free energy. These enzymes are activated when a cell receives stimulus, and
rapid conversion of lipid is observed. Phospholipase A releases fatty acid from
phospholipid and the released arachidonic acid becomes substrate for generation
of prostaglandin, leukotriene, and thromboxane and so on. And these molecules
regulate functions of cell. Phospholipase C generates diacylglycerol from
phosphatidylinositol as substrate, and the diacylglycerol as second messenger activates protein kinase C. And phospholipase D generates phosphatidic acid from
mainly phosphatidylcholine as substrate, and the phosphatidic acid induces proliferation of cell. Regulation of physiological function of cell is performed by transfer
of phosphate moiety of ATP to protein, i.e. phosphorylation of protein. Energy of
ATP is used in phosphorylation process. For example, some species of protein
kinases are activated sequentially in cycle of cell division, and proliferation and
differentiation of cell are also regulated by protein kinase. And malfunction of this
mechanism is supposed to induce cancer cell from study of oncogene. Malfunction
of protein kinase C is a candidate of canceration of cell. Phosphatidylserine, calcium
ion and diacylglycerol are required for activation of protein kinase C [16]. Protein
kinase C in cytoplasm was bound to plasma membrane when cell received a specific
stimulus [17], and calcium ion was required for binding of protein kinase C
[18]. Diacylglycerol of neutral lipid generated from negatively charged
phosphatidylinositol was supposed to promote calcium ion-induced phase separation
of phosphatidylserine in signaling of cell because of the phase separation in signaling -mimicking artificial membrane system [19]. Stimulus received by receptor
raised concentration of calcium ion from 0.2 μM to 0.6 μM in liver cell [20], and
promotion of phase separation of phosphatidylserine by diacylglycerol was also
6.4 Conversion of Membrane Lipid with Receiving Stimulus and Functions of a Cell
85