Orsini, Roberta Clara (2021) Plasma phospholipid dysregulation in patients with cystathionine β- synthase deficiency. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Plasma phospholipid dysregulation in patients with cystathionine β- synthase deficiency
Orsini, Roberta Clararoberta.orsini@alice.it
Date: 11 February 2021
Number of Pages: 43
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Clinica e Chirurgia
Dottorato: Terapie avanzate biomediche e chirurgiche
Ciclo di dottorato: 33
Coordinatore del Corso di dottorato:
Di Minno, Giovannidiminno@unina.it
Di Minno, Matteo Nicola DarioUNSPECIFIED
Date: 11 February 2021
Number of Pages: 43
Keywords: Homocystinuria, plasma untargeted lipidomics, S-adenosylmethionine, Sadenosylhomocysteine, phosphatidylethanolamine-N-methyltransferase
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Area 03 - Scienze chimiche > CHIM/03 - Chimica generale e inorganica
Area 03 - Scienze chimiche > CHIM/06 - Chimica organica
Area 06 - Scienze mediche > MED/09 - Medicina interna
Date Deposited: 24 Feb 2021 09:46
Last Modified: 07 Jun 2023 10:29
URI: http://www.fedoa.unina.it/id/eprint/13986

Collection description

Patients with cystathionine β-synthase deficiency (CBSD) exhibit extremely high circulating levels of homocysteine (Hcy) and clinical signs and symptoms whose pathophysiological understanding is poorly elucidated. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated lipid peroxidation. Although phospholipid metabolism is key for a variety of cell functions, no information is available about lipidomic profile in CBSD patients. We have characterized plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels. Using an untargeted lipidomic approach, changes in phospholipid metabolism were determined by comparing the plasma of 11 CBSD patients with that of 11 healthy subjects (CTRL). CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p=0.02), and depletion of phosphatidylcholine (PC; p=0.02) and of lysophosphatidylcholine (LPC; p=0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p=0.015) and 5.3-fold (p=0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r=0.520; p=0.019) was found. Our findings reveals e novel biochemical alteration in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE. Variations in plasma SAM and SAH concentration are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, reduction of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with CBSD.


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