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Shotgun lipidomics identifies a paired rule for the presence of isomeric ether phospholipid molecular species.

Yang K, Zhao Z, Gross RW, Han X - PLoS ONE (2007)

Bottom Line: The biochemical basis of this rule results from the fact that the enzymes which participate in either the sequential oxidation of aliphatic alcohols to fatty acids, or the reduction of long chain fatty acids to aliphatic alcohols (metabolic precursors of ether lipid synthesis), are not entirely selective with respect to acyl chain length or degree of unsaturation.Application of this rule to mass spectrometric analyses provides predictive clues to the presence of specific molecular species and greatly expands the number of identifiable and quantifiable ether lipid species present in biological samples.Through appropriate alterations in the database, use of the paired rule increases the number of identifiable metabolites in metabolic networks, thereby facilitating identification of biomarkers presaging disease states.

View Article: PubMed Central - PubMed

Affiliation: Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.

ABSTRACT

Background: Ether phospholipids are abundant membrane constituents present in electrically active tissues (e.g., heart and the brain) that play important roles in cellular function. Alterations of ether phospholipid molecular species contents are associated with a number of genetic disorders and human diseases.

Methodology/principal findings: Herein, the power of shotgun lipidomics, in combination with high mass accuracy/high resolution mass spectrometry, was explored to identify a paired rule for the presence of isomeric ether phospholipid molecular species in cellular lipidomes. The rule predicts that if an ether phospholipid A'-B is present in a lipidome, its isomeric counterpart B'-A is also present (where the ' represents an ether linkage). The biochemical basis of this rule results from the fact that the enzymes which participate in either the sequential oxidation of aliphatic alcohols to fatty acids, or the reduction of long chain fatty acids to aliphatic alcohols (metabolic precursors of ether lipid synthesis), are not entirely selective with respect to acyl chain length or degree of unsaturation. Moreover, the enzymatic selectivity for the incorporation of different aliphatic chains into the obligatory precursor of ether lipids (i.e., 1-O-alkyl-glycero-3-phosphate) is also limited.

Conclusions/significance: This intrinsic amplification of the number of lipid molecular species present in biological membranes predicted by this rule and demonstrated in this study greatly expands the number of ether lipid molecular species present in cellular lipidomes. Application of this rule to mass spectrometric analyses provides predictive clues to the presence of specific molecular species and greatly expands the number of identifiable and quantifiable ether lipid species present in biological samples. Through appropriate alterations in the database, use of the paired rule increases the number of identifiable metabolites in metabolic networks, thereby facilitating identification of biomarkers presaging disease states.

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Comparison of representative aliphatic or acyl chain profiles in different lipid domains of bovine heart.The profiles of both aliphatic chains (open column in Panel A) and fatty acyl chains (closed column in Panel A) of bovine heart ether-linked ethanolamine glycerophospholipids (PtdEtn) were derived from individual molecular species listed in Table 1. The fatty acyl chain composition of bovine heart diacyl PtdEtn (Panel B) was also calculated from the identified individual molecular species as listed in Table 1. The profile of acyl-CoA in bovine heart (Panel C) was re-plotted from previously published data [28].
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pone-0001368-g007: Comparison of representative aliphatic or acyl chain profiles in different lipid domains of bovine heart.The profiles of both aliphatic chains (open column in Panel A) and fatty acyl chains (closed column in Panel A) of bovine heart ether-linked ethanolamine glycerophospholipids (PtdEtn) were derived from individual molecular species listed in Table 1. The fatty acyl chain composition of bovine heart diacyl PtdEtn (Panel B) was also calculated from the identified individual molecular species as listed in Table 1. The profile of acyl-CoA in bovine heart (Panel C) was re-plotted from previously published data [28].

Mentions: To further uncover the abundant, but cryptic, biochemical information present in the acyl chain composition of cellular lipids, the obligatory diversity in aliphatic chain regiospecificity predicted by the paired rule in different phospholipid molecular species was exploited. The composition of O-alkyl or O-alkenyl (sn-1) chains in ether PtdEtn molecular species present in bovine heart lipid extracts demonstrated that 16∶0 (31.1 mol%), 18∶0 (34.6 mol%), and 18∶1 (22.7 mol%) moieties were predominant with smaller amounts of 17∶0, 18∶2, 16∶1, 19∶0, and 14∶0 chains (in order of decreasing abundance). Other less abundant aliphatic chains collectively accounted for only 0.5 mol% of the total bovine heart ether PtdEtn. This molecular species profile was very different from that of the acyl CoA pool in bovine heart (Figure 7C). This difference clearly indicates the selective activities of the acyl-CoA reductase and the alkyl DHAP synthase which are involved in the synthesis of the obligatory precursor of ether lipids, alkyl DHAP (Figure 8).


Shotgun lipidomics identifies a paired rule for the presence of isomeric ether phospholipid molecular species.

Yang K, Zhao Z, Gross RW, Han X - PLoS ONE (2007)

Comparison of representative aliphatic or acyl chain profiles in different lipid domains of bovine heart.The profiles of both aliphatic chains (open column in Panel A) and fatty acyl chains (closed column in Panel A) of bovine heart ether-linked ethanolamine glycerophospholipids (PtdEtn) were derived from individual molecular species listed in Table 1. The fatty acyl chain composition of bovine heart diacyl PtdEtn (Panel B) was also calculated from the identified individual molecular species as listed in Table 1. The profile of acyl-CoA in bovine heart (Panel C) was re-plotted from previously published data [28].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2147047&req=5

pone-0001368-g007: Comparison of representative aliphatic or acyl chain profiles in different lipid domains of bovine heart.The profiles of both aliphatic chains (open column in Panel A) and fatty acyl chains (closed column in Panel A) of bovine heart ether-linked ethanolamine glycerophospholipids (PtdEtn) were derived from individual molecular species listed in Table 1. The fatty acyl chain composition of bovine heart diacyl PtdEtn (Panel B) was also calculated from the identified individual molecular species as listed in Table 1. The profile of acyl-CoA in bovine heart (Panel C) was re-plotted from previously published data [28].
Mentions: To further uncover the abundant, but cryptic, biochemical information present in the acyl chain composition of cellular lipids, the obligatory diversity in aliphatic chain regiospecificity predicted by the paired rule in different phospholipid molecular species was exploited. The composition of O-alkyl or O-alkenyl (sn-1) chains in ether PtdEtn molecular species present in bovine heart lipid extracts demonstrated that 16∶0 (31.1 mol%), 18∶0 (34.6 mol%), and 18∶1 (22.7 mol%) moieties were predominant with smaller amounts of 17∶0, 18∶2, 16∶1, 19∶0, and 14∶0 chains (in order of decreasing abundance). Other less abundant aliphatic chains collectively accounted for only 0.5 mol% of the total bovine heart ether PtdEtn. This molecular species profile was very different from that of the acyl CoA pool in bovine heart (Figure 7C). This difference clearly indicates the selective activities of the acyl-CoA reductase and the alkyl DHAP synthase which are involved in the synthesis of the obligatory precursor of ether lipids, alkyl DHAP (Figure 8).

Bottom Line: The biochemical basis of this rule results from the fact that the enzymes which participate in either the sequential oxidation of aliphatic alcohols to fatty acids, or the reduction of long chain fatty acids to aliphatic alcohols (metabolic precursors of ether lipid synthesis), are not entirely selective with respect to acyl chain length or degree of unsaturation.Application of this rule to mass spectrometric analyses provides predictive clues to the presence of specific molecular species and greatly expands the number of identifiable and quantifiable ether lipid species present in biological samples.Through appropriate alterations in the database, use of the paired rule increases the number of identifiable metabolites in metabolic networks, thereby facilitating identification of biomarkers presaging disease states.

View Article: PubMed Central - PubMed

Affiliation: Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.

ABSTRACT

Background: Ether phospholipids are abundant membrane constituents present in electrically active tissues (e.g., heart and the brain) that play important roles in cellular function. Alterations of ether phospholipid molecular species contents are associated with a number of genetic disorders and human diseases.

Methodology/principal findings: Herein, the power of shotgun lipidomics, in combination with high mass accuracy/high resolution mass spectrometry, was explored to identify a paired rule for the presence of isomeric ether phospholipid molecular species in cellular lipidomes. The rule predicts that if an ether phospholipid A'-B is present in a lipidome, its isomeric counterpart B'-A is also present (where the ' represents an ether linkage). The biochemical basis of this rule results from the fact that the enzymes which participate in either the sequential oxidation of aliphatic alcohols to fatty acids, or the reduction of long chain fatty acids to aliphatic alcohols (metabolic precursors of ether lipid synthesis), are not entirely selective with respect to acyl chain length or degree of unsaturation. Moreover, the enzymatic selectivity for the incorporation of different aliphatic chains into the obligatory precursor of ether lipids (i.e., 1-O-alkyl-glycero-3-phosphate) is also limited.

Conclusions/significance: This intrinsic amplification of the number of lipid molecular species present in biological membranes predicted by this rule and demonstrated in this study greatly expands the number of ether lipid molecular species present in cellular lipidomes. Application of this rule to mass spectrometric analyses provides predictive clues to the presence of specific molecular species and greatly expands the number of identifiable and quantifiable ether lipid species present in biological samples. Through appropriate alterations in the database, use of the paired rule increases the number of identifiable metabolites in metabolic networks, thereby facilitating identification of biomarkers presaging disease states.

Show MeSH
Related in: MedlinePlus