Gradient Temperature Raman Spectroscopy of Fatty Acids with One to Six Double Bonds Identifies Specific Carbons and Provides Systematic Three Dimensional Structures
Specialized pro-resolving mediators provide promising
targets for new drugs and natural products. Much work has been accomplished on the
structure/ function of the lipoxygenase and cyclooxygenase enzymes but not on the
substrates. A better visualization of three-dimensional lipid structures will allow
increased refinement of the interactions that produce the pro-resolving mediators,
and lead to improvements in synthetic pathways. We present systematic analysis of
oleic (18:1n-9), linoleic (18:2n-6), alpha-linolenic (18:3n-3), arachidonic (20:4n-6), docosapentaenoic (22:5n-3), and docosahexaenoic (22:6n-3) acids. Continuous
gradient temperature Raman spectroscopy (GTRS) applies the temperature gradients
utilized in differential scanning calorimetry to Raman spectroscopy. GTRS can identify
and differentiate specific carbon chain sites, finally allowing Raman analysis to
explain why the long-chain polyunsaturated fatty acids (LC-PUFA) exhibit such extreme
functional differences despite minimal changes in chemical structure. Detailed vibrational
analysis of the important frequency ranges 1450
- 1200 cm-1 (includes CH2 bending and twisting) and
1750 - 1425 cm-1 (includes C=C stretching and C-C stretching plus H-C
in-plane rocking) shows for the first time that each molecule has its own characteristic
set of modes with only some redundancy/commonality. The number and frequency of
modes correlates with three-dimensional molecular structure, not the degree of unsaturation.
The high degree of specificity of lipoxygenase and cyclooxygenase enzymes should
be reconsidered in light of the fact that individual sites on the polyunsaturated
fatty acid chain are nonequivalent, and each
LC-PUFA molecule has an individual, specific
References
[1]
Broadhurst, C.L., Schmidt, W.F., Kim, M.S., Nguyen, J.K., Qin, J., Chao, K., Bauchan, G.L. and Shelton, D.R. (2016) Continuous Gradient Temperature Raman Spectroscopy of N-6DPA and DHA from -100 to 20°C. Chemistry and Physics of Lipids, 200, 1-10. https://doi.org/10.1016/j.chemphyslip.2016.06.003
[2]
Broadhurst, C.L., Schmidt, W.F., Kim, M.S., Nguyen, J.K., Qin, J., Chao, K., Bauchan, G.L. and Shelton, D.R. (2016) Continuous Gradient Temperature Raman Spectroscopy of Oleic and Linoleic Acids from -100 to 50°C. Lipids, 51, 1289-1302.
https://doi.org/10.1007/s11745-016-4194-1
[3]
Broadhurst, C.L., Schmidt, W.F., Nguyen, J.K., Qin, J., Chao, K., Aubuchon, S.R. and Kim, M.S. (2017) Continuous Gradient Temperature Raman Spectroscopy and Differential Scanning Calorimetry of N-3DPA and DHA from -100 to 10°C. Chemistry and Physics of Lipids, 204, 94-102.
[4]
Broadhurst, C.L., Schmidt, W.F., Nguyen, J.K., Qin, J., Chao, K. and Kim, M.S. (2017) Continuous Gradient Temperature Raman Spectroscopy from -100 to 40°C Yields New Molecular Models of Arachidonic Acid and 2-Arachidonoyl-1-stearoylsn-glycero-3-phosphocholine. Prostaglandins, Leukotrienes and Essential Fatty Acids, 127, 6-15. https://doi.org/10.1016/j.plefa.2017.09.019
[5]
Olsen, E.F., Rukke, E.-O., Flatten, A. and Isaksson, T. (2007) Quantitative Determination of Saturated, Monounsaturated, and Polyunsaturated Fatty Acids in Pork Adipose Tissue with Non-Destructive Raman Spectroscopy. Meat Science, 76, 628-634.
https://doi.org/10.1016/j.meatsci.2007.02.004
[6]
Bekhit, M.Y., B. Grung, B. and Mjos, S.A. (2014) Determination of Omega-3 Fatty Acids in Fish Oil Supplements Using Vibrational Spectroscopy and Chemometric Methods. Applied Spectroscopy, 68, 1190-1200. https://doi.org/10.1366/13-07210
[7]
Toledo, D.A., Roque, N.R., Teixeira, L., Milán-Garcés, E.A., Carneiro, A.B., Almeida, M.R., Andrade, G.F., Martins, J.S., Pinho, R.R., Freire-de-Lima, G.C., Bozza, P.T., D’Avila, H. and Melo, R.C. (2016) Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism. PLoS ONE, 11, e0160433. https://doi.org/10.1371/journal.pone.0160433
[8]
Killeen, D.P., Marshall, S.N., Burgess, E.J., Gordon, K.C. and Perry, N.B. (2017) Raman Spectroscopy of Fish Oil Capsules: Polyunsaturated Fatty Acid Quantitation plus Detection of Ethyl Esters and Oxidation. Journal of Agricultural and Food Chemistry, 65, 3551-3558. https://doi.org/10.1021/acs.jafc.7b00099
[9]
Dangi, B., Obeng, M., Nauroth, J.M., Teymourlouei, M., Needham, M., Raman, K. and Arterburn, L.M. (2009) Biogenic Synthesis, Purification, and Chemical Characterization of Anti-Inflammatory Resolvins Derived from Docosapentaenoic Acid (DPAn-6). The Journal of Biological Chemistry, 284, 14744-14759.
https://doi.org/10.1074/jbc.M809014200
[10]
Kohli, P. and Levy, B.D. (2009) Resolvins and Protectins: Mediating Solutions to Inflammation. British Journal of Pharmacology, 158, 960-971.
https://doi.org/10.1111/j.1476-5381.2009.00290.x
[11]
Weylandt, K.-H. (2016) Docosapentaenoic Acid Derived Metabolites and Mediators—The New World of Lipid Mediator Medicine in a Nutshell. European Journal of Pharmacology, 785, 108-115. https://doi.org/10.1016/j.ejphar.2015.11.002
[12]
Serhan, C.N. (2017) Discovery of Specialized Pro-Resolving Mediators Marks the Dawn of Resolution Physiology and Pharmacology. Molecular Aspects of Medicine, 58, 1-11. https://doi.org/10.1016/j.mam.2017.03.001
[13]
Hansen, T.V., Dalli, J. and Serhan, C.N. (2017) The Novel Lipid Mediator PD1n-3 DPA: An Overview of the Structural Elucidation, Synthesis, Biosynthesis and Bioactions. Prostaglandins & Other Lipid Mediators, 133, 103-110.
https://doi.org/10.1016/j.prostaglandins.2017.06.003
[14]
Zheng, J.S., Huang, T., Yang, J., Fu, Y.Q. and Li, D. (2012) Marine N-3 Polyunsaturated Fatty Acids Are Inversely Associated with Risk of Type 2 Diabetes in Asians: A Systematic Review and Meta-Analysis. PLoS ONE, 7, e44525.
https://doi.org/10.1371/journal.pone.0044525
[15]
Zheng, J.S., Hu, X.J., Zhao, Y.M., Yang, J. and Li, D. (2013) Intake of Fish and Marine N-3 Polyunsaturated Fatty Acids and Risk of Breast Cancer: Meta-Analysis of Data from 21 Independent Prospective Cohort Studies. BMJ, 346, e3706.
https://doi.org/10.1136/bmj.f3706
[16]
Torris, C., Molin, M. and Cvancarova-Smastuen, M. (2014) Fish Consumption and Its Possible Preventive Role on the Development and Prevalence of Metabolic Syndrome—A Systematic Review. Diabetology & Metabolic Syndrome, 6, e112.
https://doi.org/10.1186/1758-5996-6-112
[17]
Wan, Y., Zheng, J., Wang, F. and Li, D. (2017) Fish, Long Chain Omega-3 Polyunsaturated Fatty Acids Consumption, and Risk of All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis from 23 Independent Prospective Cohort Studies. Asia Pacific Journal of Clinical Nutrition, 26, 939-956.
[18]
Kuhn, H., Walther, M. and Kuban, R.J. (2002) Mammalian Arachidonate 15-Lipoxygenases Structure, Function, and Biological Implications. Prostaglandins & Other Lipid Mediators, 68-69, 263-290.
[19]
Andreou, A. and Feussner, I. (2009) Lipoxygenases: Structure and Reaction Mechanism. Phytochemistry, 70, 1504-1510.
https://doi.org/10.1016/j.phytochem.2009.05.008
[20]
Neau, D.B., Bender, G., Boeglin, W.E., Bartlett, S.G., Brash, A.R. and Newcomer, M.E. (2014) Crystal Structure of a Lipoxygenase in Complex with Substrate: The Arachidonic Acid-Binding Site of 8R-Lipoxygenase. The Journal of Biological Chemistry, 289, 31905-31913. https://doi.org/10.1074/jbc.M114.599662
[21]
Kobe, M.J., Neau, D.B., Mitchell, C.E., Bartlett, S.G. and Newcomer, M.E. (2014) The Structure of Human 15-Lipoxygenase-2 with a Substrate Mimic. The Journal of Biological Chemistry, 289, 8562-8569. https://doi.org/10.1074/jbc.M113.543777
[22]
Kuhn, H., Banthiya, S. and van Leyen, K. (2015) Mammalian Lipoxygenases and Their Biological Relevance. Biochimica et Biophysica Acta, 1851, 308-330.
[23]
Gabbs, M., Leng, S., Devassy, J.G., Monirujjaman, M. and Aukema, H.M. (2015) Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. Advances in Nutrition, 6, 513-540. https://doi.org/10.3945/an.114.007732
[24]
Liao, X., Wang, W., Fan, C., Yang, N., Zhao, J., Zhang, Y., Gao, R., Shen, G., Xia, S. and Li, G. (2017) Prokaryotic Expression, Purification and Characterization of Human Cyclooxygenase-2. International Journal of Molecular Medicine, 40, 75-82.
https://doi.org/10.3892/ijmm.2017.3007
[25]
Qin, J., Chao, K. and Kim, M.S. (2010) Raman Chemical Imaging System for Food Safety and Quality Inspection. Transactions of the American Society of Agricultural and Biological Engineers, 53, 1873-1882.
