Glycerol in the body can be chemically converted to triacylglycerides and phospholipids PL which are chiral, and which exist in one enantiomeric form. How can this be possible if the two CH2OH groups on glycerol are identical? It turns out that even though these groups are stereochemically equivalent, we can differentiate them as follows. Orient glycerol with the OH on C2 pointing to the left.
Now the two alcohol substituents on C1 and C3 are not identical and the resulting molecule is chiral. Hence we say that C1 is the proS carbon.
Hence C3 is the proR carbon. This shows that in reality we can differentiate between the two identical CH2OH substituents. We say that glycerol is not chiral, but prochiral. Think of this as glycerol has the potential to become chiral by modifying one of two identical substituents. We can relate the configuation of glycerol above, when OH on C2 is pointing to the left to the absolute configuration of L-glyceraldehyde, a simple sugar a polyhydroxyaldehyde or ketone , another 3C glycerol derivative.
A recent study revealed associations of phospholipase A 2 , LPC, lysophosphatidic acid and proinflammatory cytokine levels in atherosclerotic plaques, suggesting involvement of LPC in plaque inflammation and vulnerability [10]. It was shown recently that total PC and TG are elevated in hypertensive patients and that antihypertensive agents reduce plasma total cholesteryl esters and TG [11]. Obesity leads to increased lipid load in plasma, while IR controlled for body mass index BMI has little effects on plasma lipid composition.
Furthermore several additional loci associated with phospholipid species were identified, among those key enzymes involved in lipid metabolic processes like beta oxidation, polyunsaturated FA PUFA synthesis, TG breakdown and receptor-mediated lipoprotein uptake [13] , [15]. An overview of published SNP-lipid species correlations related to vascular and metabolic disease was recently published [16].
Sphingolipids are localized in cell and organelle membranes and lipoproteins and are suggested to exert important functions in cell signaling, cell surface protection, protein and lipid transport and sorting. Recent publications highlight their roles in both health and disease including cardiovascular disease [18] , [19].
Cer occupies the central position in sphingolipid metabolism. Both, palmitate and stearate, have been shown to induce apoptosis in cultured cells [21] — [23] and part of cardiomyocyte loss in genesis or progression of heart failure in humans is mediated by apoptosis [24]. As FA-induced apoptosis is specific for these two FAs [22] it has been suggested that FA-induced apoptosis is mediated by Cer synthesis. While this appears to be true for some cell types [22] , [23] other data indicate that Cer is not causal for FA-induced apoptosis [25] but may enhance the effect [25].
Cer, IR and inflammation are suggested to be linked via an IL-6 related mechanism. Cer may also influence induction of inflammation that is involved in IR states that are often found with coronary heart disease [26]. Furthermore elevated plasma Cer levels were found to be correlating with hypertension grade [27].
Previously, free FA levels were identified as independent predictors of total and cardiovascular mortality and as independent risk factors for future sudden cardiac death in the Ludwigshafen Risk and Cardiovascular Health LURIC study [29] , [30]. In brief it included patients of Caucasian origin hospitalized for coronary angiography between June and May Written informed consent was obtained from each of the participants. Clinical indications for angiography were chest pain or non-invasive tests consistent with myocardial ischemia.
To limit clinical heterogeneity, individuals suffering from acute illness other than acute coronary syndromes, chronic non-cardiac diseases and a history of malignancy within the five past years were excluded.
Criteria for the definition of CAD were recently published [32]. Anthropometric and clinical parameters of the examined cohort were previously published [33] and a short summary is shown in table 1. For each lipid class two non-naturally occurring internal standards were added and quantification was achieved by calibration lines generated by addition of naturally occurring lipid species to plasma.
Deisotoping and data analysis for all lipid classes was performed by self programmed Excel Macros according to the principles described previously [34].
Glycerophospholipid species were annotated based on assumption of even numbered carbon chains only. All lipid variables were logarithmically transformed and divided by their respective standard deviation to achieve a normal distribution prior to analyses. Cox proportional hazards regression was applied to assess the effect of molecular lipids on total and cardiovascular mortality during a median follow-up of 8 years. The six molecular lipid species which showed the strongest protective effect and the six molecular lipid species that showed the highest risk increment were summed up to create a protective lipids score and a risk lipids score, respectively.
We then calculated the ratio of risk lipids to protective lipids and assessed the association with mortality per 0. The SPSS statistical package version Our cohort included controls and CAD positive patients.
From the patients had survived a myocardial infarction prior to enrollment in the study. The CAD group was significantly older than the control group, showing significantly higher prevalence for type 2 diabetes, smoking, and hypertension.
All identified species were similarly associated with total and CAD mortality Figure 1 — 3. All protective PC species showed overall a slightly higher assocition with death due to CAD than to total mortality. Species with significant association to CAD and total mortality are shown. Positive association with CAD is shown in grey and positive association with total mortality in black.
Negative association with CAD is shown by a dashed white bar and negative association with total mortality in white. Species are named according to the number of carbon atoms and degree of desaturation. Besides their association the mean concentration and standard deviation are shown. PC and LPC species were annotated based on assumption of even numbered carbon chains only. PE species were annotated based on assumption of even numbered carbon chains only.
Besides their association the mean concentration and standard deviation are shown together with the putative involved Cer-synthase.
The remaining 16 PE species were positively associated with mortality, independent of chain length and degree of saturation. In summary highly polyunsaturated PC species together with LPC species and long chain saturated SM species seem to be associated with a protective role.
Finally we tested if the combination of certain lipid species increased their prognostic value. The result of that were hazard ratios of 2. Diabetes, CAD and age per 10 years increase showed an approximately 2-fold increase; hypertension, CRP and male sex showed an approximately 1. The quotient of the sums of protective and risk lipid species on the other hand showed an almost 3-fold increased risk.
In this study we provide data that plasma glycerophospholipid and sphingolipid species are easily accessible predictors of mortality. This is in agreement with studies suggesting that deregulation of SCD supports inflammation, atherosclerosis, hypertriglyceridemia, and metabolic syndrome [38].
The nseries is endogenously derived from stearate. The nseries is endogenously derived from palmitate. Adapted from A type of lipids that associate the cell membranes are referred to as sphingolipids. They are based on an eighteen carbon amine alcohol. In simple terms, sphingolipids contain organic aliphatic amino alcohol sphingosine or any substance that resembles the sphingosine.
All the members that belong to the group sphingolipids contain a complex or simple sugar that is attached to the first carbon of the alcohol group C1. The member that deviates from this common structure is sphingomyelin. This molecule consists of a phosphorylcholine group that is the same polar head group present in phosphatidylcholine. Since sphingomyelin does not contain the sugar moiety, it is considered as an analog to phosphatidylcholine. In addition to the sugar, all sphingolipids contain a fatty acid, which is attached to the amino group of the sphingosine molecule.
The sphingomyelin is the only sphingolipid that is considered as a phospholipid that functions as a major component of biological membranes. The sphingomyelin is the only phosphorous containing sphingolipids that are present in abundant forms in the nervous tissue. Sphingomyelins also present in the blood. Sphingolipidosis and sphingolipodystrophy are two disease conditions that are developed due to abnormal sphingolipid metabolism.
Due to the accumulation of sphingolipids in the brain, there can be a development of a rare disease called Tay Sachs disease condition.
Cell membranes are important structures that separate the internal cell environment from the external environment. They are made up of different constituents such as Glycerophospholipids and Sphingolipids. Glycerophospholipds are considered as the main constituents of the lipid bilayer. Sphingolipids are another class of lipids that associate the membranes.
All the members that belong to the group sphingolipids contain a complex or simple sugar that is attached to the alcohol on the first carbon except sphingomyelin. Both contain fatty acids in their structure. This is the difference between Glycerophospholipids and Sphingolipids. Rodriguez-Cuenca, S.
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