Metabolism, Physiology, and Analyses of Primary Fatty Acid Amides

Divito, Erin B; Cascio, Michael

doi:10.1021/cr300363b

Cited by 46 publications

(28 citation statements)

References 96 publications

(130 reference statements)

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“…Strong associations between aberrant regulation of FAAH/FAAH2 and alcohol and substance dependency, as well as obesity [85] have been made. The overexpression of FAAH/FAAH2 also associates with sleep deprivation [58] as well as cholesterol level maintenance [86]. Incidentally, the index patient NWU001 experienced a number of symptoms which seem to correlate with the transcriptome footprint and abovementioned literature.…”

Section: Discussionmentioning

confidence: 75%

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Biochemical Characterisation and Whole Genome Expression Profiling of Cultured Skin Fibroblasts from Two South African Adults with Urinary 3-Hydroxyisovaleric Acid and 3-Methylcrotonylglycine

Berg¹,

Erasmus²,

Suormala³

et al. 2016

J Rare Disord Diagn Ther

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We report on the first case of marginal 3-methylcrotonyl-CoA carboxylase (MCC) deficiency in South Africa. Urinary 3-hydroxyisovaleric acid and 3-methylcrotonylglycine were detected in four males of a non-consanguineous family. Only the index patient (NWU001) had non-specific symptoms, the others were asymptomatic. The inherited metabolite profile and partially reduced MCC activity were indicative of marginal MCC deficiency. In vivo L-leucine loading confirmed a reduced flux through the leucine degradation pathway. No known deleterious mutations were detected in the open reading frames of MCCC1 and MCCC2. NWU001 was heterozygous for a SNP in MCCC1 (rs2270968; c.1391A>C, p.H464P). NWU002 was heterozygous for a MCCC2 splice variant which skips exon 7 and causes an in frame deletion of 38 amino acids that is identical to a predicted shorter MCCC2 isoform-2 (Q9HCC0-2). Whole genome expression profiles from cultured skin fibroblasts of NWU001 and NWU002 and two healthy adults using Affymetrix ® HuExST1.0 arrays detected 14237 significantly differentially expressed transcript IDs of which only 1277 have known annotation and gene association. The underlying molecular interactions, secondary signalling responses and functional relationships of these 1277 transcripts were inspected following a knowledge-based functional analyses approach using Ingenuity Pathway Analysis software. The transcriptome had a footprint of oxidative stress, disruption of energy homeostasis, inflammation, impaired cellular maintenance and repair mechanisms. Of note was the significant up regulation of the fatty acid amide hydrolase variant 2 (FAAH2) HuChrX transcript in the anandamide degradation canonical pathway. The observations that the two MCC transcripts were not significantly differentially expressed and that more than 90% of the significantly differently expressed transcripts are still poorly annotated further support the notion that secondary factors other than the MCC loci impact on the MCC deficiency phenome.

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Section: Discussionmentioning

confidence: 75%

“…These enzymes convert fatty acid amides to ethylamine and the corresponding fatty acid. While FAAH seems to prefer poly-unsaturated fatty acid amides as substrates, it seems as if FAAH2 is more specific for mono-unsaturated fatty acid amides [58]. However, FAAH2 is not yet well characterised.…”

Section: Functional Analysis Of the Huchrx Transcript Subsetmentioning

confidence: 99%

Biochemical Characterisation and Whole Genome Expression Profiling of Cultured Skin Fibroblasts from Two South African Adults with Urinary 3-Hydroxyisovaleric Acid and 3-Methylcrotonylglycine

Berg¹,

Erasmus²,

Suormala³

et al. 2016

J Rare Disord Diagn Ther

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“…Cyt c in its native structure can interact with certain kinds of lipids, such as catalyzing the fatty acid amidation reaction. 31 The fact that cytochrome c can interact with the lipid bilayer has been known for tens of years, 32 even before the term "apoptosis" was dened.…”

Section: Binding To Lipids and Lipid Containing Membranesmentioning

confidence: 99%

“…At this stage, cyt c only slightly penetrates into the membrane. However, 31 P NMR shows that the binding with cyt c will cause the generation of non-bilayer structures or lateral phase separation of enriched acidic phospholipids, especially in cardiolipin bilayer regions. At the same time, ESR or resonance Raman spectroscopy suggests that cyt c, upon binding with lipids, will undergo a backbone structural change around or within the heme part.…”

Section: Binding To Lipids and Lipid Containing Membranesmentioning

confidence: 99%

Double-edged sword in cells: chemical biology studies of the vital role of cytochrome c in the intrinsic pre-apoptotic mitochondria leakage pathway

et al. 2015

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Besides functioning as an electron transporter in the mitochondrial electron transport chain, cytochrome c (cyt c) is also one of the determinants in the execution of cell death. The interaction between cyt c and lipids has long been of great interest in biological systems, while the study of cyt c has attracted even more attention since its new function in apoptosis was discovered. Theories on the cause-effect signaling pathways have been proposed. However, until recently, some of the detailed parts have remained poorly understood in the big picture of cyt c-mediated apoptosis. In the past few years, new labelling, monitoring and detecting methods as well as in vitro model systems such as cyt c-cardiolipin (CL) or cyt c-membrane systems have been developed to overcome these drawbacks. The discovery of the versatile roles of cyt c in metabolic as well as apoptotic processes suggests cyt c per se as a potential drug target. In this review, we divide the whole cyt c-mediated pre-apoptotic mitochondrial leakage process into several sections in a chronological order and summarize the recent discoveries and hypotheses. With the combinatorial effort of modern interdisciplinary subjects such as chemical biology, bio-inorganic chemistry, structural biology and physical organic chemistry, we expect that researches in this field will shed light on our understanding of the whole intrinsic apoptotic process, and further contribute to health sciences.

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“…In this study, we have focused attention on fatty acyls (for review see Divito and Cascio, 2013). N-acyl ethanolamines (NAEs) have a long history of physiological and G-protein coupled receptor mediated effects that are directly related to, or reminiscent of, cannabinoid activation (Lambert et al, 2002; Ahn et al, 2008; Luchicchi and Pistis, 2012; Mechoulam and Parker, 2013).…”

Section: Introductionmentioning

confidence: 99%

Multidimensional Liquid Chromatography Coupled with Tandem Mass Spectrometry for Identification of Bioactive Fatty Acyl Derivatives

Divito¹,

Kroniser²,

Cascio³

2016

Front. Physiol.

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Recognition of the contributions of lipids to cellular physiology, both as structural components of the membrane and as modulatory ligands for membrane proteins, has increased in recent years with the development of the biophysical and biochemical tools to examine these effects. Their modulatory roles in ion channels and transporters function have been extensively characterized, with the molecular mechanisms of these activities being the subject of intense scrutiny. The physiological significance of lipids in biochemistry is expanding as numerous fatty acyls are discovered to possess signaling properties. These bioactive lipids are often found in quantities of pmol/g of tissue and are co-extracted with numerous lipophilic molecules, making their detection and identification challenging. Common analytical methodologies involve chromatographic separation and mass spectrometric techniques; however, a single chromatographic step is typically ineffective due to the complexity of the biological samples. It is, therefore, essential to develop approaches that incorporate multiple dimensions of separation. Described in this manuscript are normal phase and reversed phase separation strategies for lipids that include detection of the bioactive primary fatty acid amides and N-acyl glycines via tandem mass spectrometry. Concerted utilization of these approaches are then used to separate and sensitively identify primary fatty acid amides extracted from homogenized tissue, using mouse brains as a test case.

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Metabolism, Physiology, and Analyses of Primary Fatty Acid Amides

Cited by 46 publications

References 96 publications

Biochemical Characterisation and Whole Genome Expression Profiling of Cultured Skin Fibroblasts from Two South African Adults with Urinary 3-Hydroxyisovaleric Acid and 3-Methylcrotonylglycine

Biochemical Characterisation and Whole Genome Expression Profiling of Cultured Skin Fibroblasts from Two South African Adults with Urinary 3-Hydroxyisovaleric Acid and 3-Methylcrotonylglycine

Double-edged sword in cells: chemical biology studies of the vital role of cytochrome c in the intrinsic pre-apoptotic mitochondria leakage pathway

Multidimensional Liquid Chromatography Coupled with Tandem Mass Spectrometry for Identification of Bioactive Fatty Acyl Derivatives

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