Abstract:
:Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.
journal_name
Proc Natl Acad Sci U S Aauthors
Payne F,Lim K,Girousse A,Brown RJ,Kory N,Robbins A,Xue Y,Sleigh A,Cochran E,Adams C,Dev Borman A,Russel-Jones D,Gorden P,Semple RK,Saudek V,O'Rahilly S,Walther TC,Barroso I,Savage DBdoi
10.1073/pnas.1408523111subject
Has Abstractpub_date
2014-06-17 00:00:00pages
8901-6issue
24eissn
0027-8424issn
1091-6490pii
1408523111journal_volume
111pub_type
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