Peter J. Crick

Rare Cholesterol Related Disorders – A Sterolomic Library for Diagnosis and Monitoring of Diseases

Mohsen Ali Asgari, Eylan Yutuc, Jonas Abdel‐Khalik, Peter J. Crick et autres

Abstract Cholesterol is an essential molecule in all animals, it can be made by de novo synthesis and can be taken up from the diet. Inherited disorders of cholesterol synthesis, metabolism and transport lead to disease, often with neurological signs. However, such …

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The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson’s Disease and Their Association With Disease State and Clinical Features

William James Griffiths, Jonas Abdel‐Khalik, Sarah F. Moore, Ruwani Wijeyekoon et autres

Disordered cholesterol metabolism is linked to neurodegeneration. In this study we investigated the profile of cholesterol metabolites found in the cerebrospinal fluid (CSF) of Parkinson's disease (PD) patients. When adjustments were made for confounding variables of age and sex, 7α,(25R)26-dihydroxycholesterol and a …

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Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates

Jonas Abdel‐Khalik, Tom Hearn, Alison L. Dickson, Peter J. Crick et autres

-unsaturated bile acids in plasma and urine of patients with Smith-Lemli-Opitz syndrome (SLOS), a defect in cholesterol biosynthesis resulting in elevated levels of 7-dehydrocholesterol (7-DHC), an immediate precursor of cholesterol. Using liquid chromatography - mass spectrometry (LC-MS) we have uncovered a pathway …

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Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse

Peter J. Crick, Eylan Yutuc, Jonas Abdel‐Khalik, Ahmed Saeed et autres

While the presence and abundance of the major oxysterols and cholestenoic acids in the circulation is well established, minor cholesterol metabolites may also have biological importance and be of value to investigate. In this study by observing the metabolism of deuterium-labelled cholesterol …

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Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders

William James Griffiths, Eylan Yutuc, Jonas Abdel‐Khalik, Peter J. Crick et autres

Cholestane-3β,5α,6β-triol (3β,5α,6β-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7β-hydroxycholesterol (7β-HC) can also be formed by free radical oxidation of cholesterol. Here we …

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Mining for Oxysterols in Cyp7b1−/− Mouse Brain and Plasma: Relevance to Spastic Paraplegia Type 5

Anna Meljon, Peter J. Crick, Eylan Yutuc, Joyce L.W. Yau et autres

Deficiency in cytochrome P450 (CYP) 7B1, also known as oxysterol 7α-hydroxylase, in humans leads to hereditary spastic paraplegia type 5 (SPG5) and in some cases in infants to liver disease. SPG5 is medically characterized by loss of motor neurons in the corticospinal …

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First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid-chromatography–Urgent need for harmonisation of analytical methods

Dieter Lütjohann, Ingemar Björkhem, Silvia Friedrichs, Anja Kerksiek et autres

Serum concentrations of lathosterol, the plant sterols campesterol and sitosterol and the cholesterol metabolite 5α-cholestanol are widely used as surrogate markers of cholesterol synthesis and absorption, respectively. Increasing numbers of laboratories utilize a broad spectrum of well-established and recently developed methods for …

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Developing an Enzyme-Assisted Derivatization Method for Analysis of C27 Bile Alcohols and Acids by Electrospray Ionization-Mass Spectrometry

Jonas Abdel‐Khalik, Peter J. Crick, Eylan Yutuc, Yuqin Wang et autres

Enzyme-assisted derivatization for sterol analysis (EADSA) is a technology designed to enhance sensitivity and specificity for sterol analysis using electrospray ionization–mass spectrometry. To date it has only been exploited on sterols with a 3β-hydroxy-5-ene or 3β-hydroxy-5α-hydrogen structure, using bacterial cholesterol oxidase enzyme …

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Additional pathways of sterol metabolism: Evidence from analysis of Cyp27a1−/− mouse brain and plasma

William James Griffiths, Peter J. Crick, Anna Meljon, Spyridon Theofilopoulos et autres

Cytochrome P450 (CYP) 27A1 is a key enzyme in both the acidic and neutral pathways of bile acid biosynthesis accepting cholesterol and ring-hydroxylated sterols as substrates introducing a (25R)26-hydroxy and ultimately a (25R)26-acid group to the sterol side-chain. In human, mutations in …

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Bile Acid Biosynthesis Avoiding Cholesterol

William James Griffiths, Jonas Abdel‐Khalik, Peter J. Crick, Eylan Yutuc et autres

Abstract Bile acids are the end products of cholesterol metabolism secreted into bile. They are essential for the absorption of lipids and lipid soluble compounds from the intestine. Here we have investigated the bile acid content of plasma and urine from patients …

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International descriptive and interventional survey for oxycholesterol determination by gas- and liquid-chromatographic methods

Dieter Lütjohann, Ingemar Björkhem, Silvia Friedrichs, Anja Kerksiek et autres

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Identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in human cerebrospinal fluid and plasma

Jonas Abdel‐Khalik, Peter J. Crick, Eylan Yutuc, Andrea E. DeBarber et autres

Dihydroxyoxocholestenoic acids are intermediates in bile acid biosynthesis. Here, using liquid chromatography - mass spectrometry, we confirm the identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in cerebrospinal fluid (CSF) based on comparisons to authentic standards and of 7α,12α-dihydroxy-3-oxocholest-4-en-26-oic and 7α,x-dihydroxy-3-oxocholest-4-en-26-oic (where hydroxylation is …

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