Lipids

, Volume 32, Issue 4, pp 351–358 | Cite as

Phospholipid biosynthetic enzymes in human brain

  • Brian M. Ross
  • Anna Moszczynska
  • Jan K. Blusztajn
  • Allan Sherwin
  • Andres Lozano
  • Stephen J. Kish
Article

Abstract

Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis. However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect. Thus, the objective of our study was to characterize the enzymes involved, in particular, whether differences existed in the relative affinity of substrates for the enzymes of phosphatidylethanolamine (PE) compared to those of phosphatidylcholine (PC) synthesis. The concentration of choline in rapidly frozen human brain biopsies ranged from 32–186 nmol/g tissue, a concentration similar to that determined previously for ethanolamine. Since human brain ethanolamine kinase possessed a much lower affinity for ethanolamine (Km=460 μM) than choline kinase did for choline (Km=17 μM), the activity of ethanolamine kinase in vivo may be more dependent on substrate availability than that of choline kinase. In addition, whereas ethanolamine kinase was inhibited by choline, and to a lesser extent by phosphocholine, choline kinase activity was unaffected by the presence of ethanolamine, or phosphoethanolamine, and only weakly inhibited by phosphocholine. Phosphoethanolamine cytidylyl-transferase (PECT) and phosphocholine cytidylyltransferase (PCCT) also displayed dissimilar characteristics, with PECT and PCCT being located predominantly in the cytosolic and particulate fractions, respectively. Both PECT and PCCT exhibited a low affinity for CTP (Km approximately 1.2 mM), suggesting that the activities of these enzymes, and by implication, the rate of phospholipid synthesis, are highly dependent upon the cellular concentration of CTP. In conclusion, our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more dependent upon substrate (ethanolamine) availability than that of PC synthesis.

Abbreviations

PC

phosphatidylcholine

PCCT

phosphocholine cytidylyltransferase

PE

phosphatidylethanolamine

PECT

phosphoethanolamine cytidylyltransferase

TLC

thin-layer chromatography

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Copyright information

© AOCS Press 1997

Authors and Affiliations

  • Brian M. Ross
    • 1
  • Anna Moszczynska
    • 5
  • Jan K. Blusztajn
    • 3
  • Allan Sherwin
    • 4
  • Andres Lozano
    • 2
  • Stephen J. Kish
    • 1
    • 5
  1. 1.Department of PsychiatryUniversity of TorontoTorontoCanada
  2. 2.Toronto HospitalTorontoCanada
  3. 3.Department of PathologyBoston University Medical SchoolBoston
  4. 4.Montreal Neurological InstituteMontrealCanada
  5. 5.Human Neurochemical Pathology LaboratoryClarke Institute of PsychiatryTorontoCanada

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