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Phospholipid‐Metabolizing Enzymes in Alzheimer's Disease: Increased Lysophospholipid Acyltransferase Activity and Decreased Phospholipase A 2 Activity
Author(s) -
Ross Brian M.,
Moszczynska Anna,
Erlich Jeffrey,
Kish Stephen J.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020786.x
Subject(s) - phospholipid , acyltransferase , phosphocholine , biochemistry , biology , phosphodiesterase , neurodegeneration , plasmalogen , phospholipase a1 , choline kinase , phospholipase a2 , catabolism , medicine , endocrinology , chemistry , phosphatidylcholine , enzyme , membrane , disease
Damage to brain membrane phospholipids may play an important role in the pathogenesis of Alzheimer's disease (AD); however, the critical metabolic processes responsible for the generation and repair of membrane phospholipids affected by the disease are unknown. We measured the activity of key phospholipid catabolic and anabolic enzymes in morphologically affected and spared areas of autopsied brain of patients with AD and in matched control subjects. The activity of the major catabolic enzyme phospholipase A 2 (PLA 2 ), measured in both the presence and absence of Ca 2+ , was significantly decreased (−35 to −53%) in parietal and temporal cortices of patients with AD. In contrast, the activities of lysophospholipid acyltransferase, which recycles lysophospholipids into intact phospholipids, and glycerophosphocholine phosphodiesterase, which returns phospholipid catabolites to be used in phospholipid resynthesis, were increased by ∼50–70% in the same brain areas. Brain activities of enzymes involved in de novo phospholipid synthesis (ethanolamine kinase, choline kinase, choline phosphotransferase, phosphoethanolamine cytidylyltransferase, and phosphocholine cytidylyltransferase) were either normal or only slightly altered. The activities of PLA 2 and acyltransferase were normal in the degenerating cerebellum of patients with spinocerebellar atrophy type 1, whereas the activity of glycerophosphocholine phosphodiesterase was reduced, suggesting that the alterations in AD brain were not nonspecific consequences of neurodegeneration. Our data suggest that compensatory phospholipid metabolic changes are present in AD brain that reduce the rate of phospholipid loss via both decreased catabolism (PLA 2 ) and increased phospholipid resynthesis (acyltransferase and glycerophosphocholine phosphodiesterase).