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Phospholipids

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Nice animated overview of phospholipid structure and how these fats are important to cell membranes:

Lipoprotein Structures

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Here we have assembled some papers and thoughts that examine the structure of lipoproteins:

Apo A-1:

Wu et al. 2007. The refined structure of nascent HDL reveals a key functional domain for particle maturation and dysfunction. Nature Structural & Molecular Biology. 14: 861-868.

Apo B-100:

Segrest JP et al. 2001. Structure of apoliprotein B-100 in LDL. Journal of Lipid Research. 42: 1346-1367.

LDLr:

Jeon H & Blacklow SC. 2005. Structure and physiological function of the LDLr. Annual Review of Biochemistry. 74: 535-562.

 

LDL

Can be produced directly 1

Small VLDL2 / large IDL1 lead to mid sized LDL2, while small IDL2which is similar in size and density to large LDL1, is the metabolic precursor to these particles. IDL1 is part of a delipidation cascade, thus we go VLDL->IDL -> LDL, but IDL2 is directly secreted (possibly in the liver), and thus the arising LDL remains in the same size and density region.

References

1Gaw, A., C. J. Packard, G. M. Lindsay, B. A. Griffin, M. J. Caslake, A. R. Lorimer, and J. Shepherd. 1995. Overproduction of small very low density lipoproteins (Sf 20–60) in moderate hypercholesterolemia: relationships between apolipoprotein B kinetics and plasma lipoproteins. J. Lipid Res. 36: 158–171.

ApoB

Secreted throughout the VLDL-LDL-IDL spectrum 1,2,3. Inversely related to TGs4, such that at low TG ApoB is released as IDL / LDL but at high TG 90% of ApoB is secreted in VLDL

References

1Fisher, W. R., L. A. Zech, L. L. Kilgore, and P. W. Stacpoole. 1991.Metabolic pathways of apolipoprotein B in heterozygous familial hypercholesterolemia: studies with a [3H]leucine tracer. J. Lipid Res. 32: 1823–1836.

2Soutar, A. K., N. B. Myant, and G. R. Thompson. 1977. Simultaneous measurement of apolipoprotein B turnover in very-lowand low-density lipoproteins in familial hypercholesterolaemia. Atherosclerosis. 28: 247–256.

3Nakaya, N., B. H. Chung, J. R. Patsch, and O. D. Taunton. 1977. Synthesis and release of low density lipoproteins by the isolated perfused pig liver. J. Biol. Chem. 252: 7530–7533.

4Packard, C. J., T. Demant, J. P. Stewart, D. Bedford, M. J. Caslake, G. Schwertfeger, A. Bedynek, J. Shepherd, and D. Seidel. 2000. Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. J. Lipid Res. 41: 305–318.

VLDL

Large VLDL (VLDL1) have less cholesterol ester and more triglyceride.

VLDL2 largely arises from VLDL1 as indicated by by a 90% reduction is rate of this conversion in lipoprotein lipase deficiency1,2 although some also arises from the liver.

Uptake of VLDL, that has not been degraded into VLDL remnants, may occur through the VLDL receptor3, dependent on ApoE. LRP receptor may uptake VLDL remnants4. An inverse relationship between VLDL size and LDL size has been suggested 5, although this has not been substantiated by my own, more recent research 6

References
1Packard, C. J., A. Gaw, T. Demant, and J. Shepherd. 1995. Development and application of a multicompartmental model to study very low density lipoprotein subfraction metabolism.J. Lipid Res.36:172–187.

2Stalenhoef, A. F., M. J. Malloy, J. P. Kane, and R. J. Havel. 1984. Metabolism of apolipoproteins B-48 and B-100 of triglyceriderich
lipoproteins in normal and lipoprotein lipase-deficient humans. Proc. Natl. Acad. Sci. USA. 81: 1839–1843.

3Tacken, P. J., B. Teusink, M. C. Jong, D. Harats, L. M. Havekes, K. W. van Dijk, and M. H. Hofker. 2000. LDL receptor deficiency unmasks altered VLDL triglyceride metabolism in VLDL receptor transgenic and knockout mice. J. Lipid Res. 41: 2055–2062.

4Hussain, M. M., F. R. Maxfield, J. Mas-Oliva, I. Tabas, Z. S. Ji, T. L. Innerarity, and R. W. Mahley. 1991. Clearance of chylomicron remnants by the low density lipoprotein receptor-related protein/ alpha 2-macroglobulin receptor. J. Biol. Chem. 266: 13936–13940.

5 Ref missing

6Wood, A.C., Glasser, S., Garvey, W.T., Kabagambe, E.K., Borecki, I.E., Tiwari, H.K., Tsai, M., Hopkins, P., Ordovas, J., & Arnett, D. K., How do VLDL, LDL and HDL lipoprotein diameters cluster across the components of the metabolic syndrome? submitted

LRP receptor

Uptakes chylomicron remnants and VLDL remnants.

Triglycerides

Variation in plasma TG mainly varies with levels of VLDL1 levels 1. This variation affects how ApoB is secreted – at low TG, ApoB is secreted as IDL or LDL, at high levels of TG it is secreted as VLDL.

High TG should lead to increased VLDL, and increased LDL from delipidation cascades, it should reduce the amount of directly synthesized LDL. LDL that is directly synthesized is larger than that which is a VLDL remnant, therefore reducing TG levels, should lead to an increased in the overall size of LDL.

References
1Gofman, J. W., O. Delalla, F. Glazier, N. K. Freeman, D. Lindgren, A. V. Nichols, B. Strisower, and A. R. Tramplin. 1954. The serum lipoprotein transport system in health, metabolic disorders, atherosclerosis and coronary artery disease. Plasma. 2: 413–484.

ApoC-III

Interacts with (to inhibit) or displaces ApoE1,2,3,4

References

1Aalto-Setala, K., E. A. Fisher, X. Chen, T. Chajek-Shaul, T. Hayek, R. Zechner, A. Walsh, R. Ramakrishnan, H. N. Ginsberg, and J. L. Breslow. 1992. Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apoCIII and reduced apoE on the particles. J. Clin. Invest. 90: 1889–1900.

2Windler, E., Y. Chao, and R. J. Havel. 1980. Regulation of the hepatic uptake of triglyceride-rich lipoproteins in the rat. Opposing effects of homologous apolipoprotein E and individual C apolipoproteins. J. Biol. Chem. 255: 8303–8307.

3Windler, E., Y. Chao, and R. J. Havel. 1980. Determinants of hepatic uptake of triglyceride-rich lipoproteins and their remnants in the rat. J. Biol. Chem. 255: 5475–5480.

4Windler, E., and R. J. Havel. 1985. Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. J. Lipid Res. 26: 556–565.

ApoE

Ligand for the VLDL receptor, which uptakes VLDL

Inhibited by ApoC-III

Papers I have enjoyed

This blog-iki (blog because I don’t know how to make a wiki properly) is not intended to be original, citeable material. Rather just an online resource for collected notes on lipid reading I / we have conducted. Therefore below is a list of papers that have largely contributed to the knowledge herein:

Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002;43:1363-79: Great article on the origin of small, dense LDLs