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Lipoprotein


DATA No : TLP3001 INFORMANT : Kazuo Kondo

NAME : lipoprotein (a)

COMMON NAME:
SYMBOL: Lp(a)
FORMULA: MOL.WT (average) :
BIOLOGICAL ACTIVITY
Biological activities
There is substantial evidence for an association between serum Lp(a) concentration and myocardial infarction. Most of this evidence is from case control rather than prospective studies. There is also evidence that serum Lp(a) is related to the extent of coronary artery disease assessed angiographically. It is often stated that Lp(a) is a strong independent indicator of coronary heart disease risk. (Ref. 3009/3010/3011)
PHYSICAL AND CHEMICAL PROPERTIES
MELTING POINT:Definition
Lp(a) can be defined as a lipoprotein particle having as a protein moiety apolipoprotein B-100(the protein associated with low-density lipoprotein) disulfide-linked to apolipoprotein(a), the distinctive glycoprotein of Lp(a) that is homologous to plasminogen(Ref. 3001/3002/3003/3004)

BOILING POINT:

REFRACTIVE INDEX:

OPTICAL ROTATION:

DENSITY:

SOLUBILITY:Physical properties
Mean Diameter 21-26 nm
Relative weight composition %
Protein30.9}0.8 Phospholipid 19.0}0.2 Free cholesterol 7.9}1.8 Cholesterol ester 37.1}1.6 Triglyceride 8.0}5.3
Density
1.05-1.21g/mL(Ref. 3005)
SPECTRAL DATA
UV SPECTRA:

IR SPECTRA:

NMR SPECTRA:

MASS SPECTRA:

OTHER SPECTRA:
CHROMATOGRAM DATA
Western blotting
Fig.Western blotting of Lp(a) phenotypes and antisera
[Chromatogram 3001]
SOURCE
Characterization
Lp(a) particles, first identified in human plasma by K. Berg in 1963(Ref. 3006), are similar to low-density lipoproteins (LDL), containing apolipoprotein B-100 (apo B-100) and a similar lipid content. In addition, Lp(a) contains the glycoprotein apolipoprotein(a) (apo (a)), which is disulfide-linked to apo B-100(Ref. 3001).
CHEMICAL SYNTHESIS
Structure
Lp(a) is made up of a low-density lipoprotein-like structure in which apolipoprotein B-100, the protein moiety of authentic low-density lipoprotein, is covalently linked to a glycoprotein, apolipoprotein (a) ,which is the specific marker of Lp (a) that exhibits a striking similarity to plasminogen. The dominant structural motif of apo (a) is the kringle, a three-disulfide, triple-loop structure named for its resemblance to a Danish pretzel. Kringle 4 is repeated 13 to 37 times, whereas there is only one kringle 5. It is now established that the size of each apo (a) isoform is under strict genetic control and determined by the number of kringles that it contains. Usually, there is 1 mol of apo (a) and 1 mol of apo B-100 in each Lp(a) particle. However, species of Lp (a) having one copy of apo B-100 and 2mol of apo (a) have been reported.
Composition
Lp(a) is heterogeneous, both within and among individuals, and this heterogeneity may at least partly be accounted for by differences in the size of apo (a). The Mr of apo (a) varies among individuals, and no fewer than six isoforms with Mr ranging from 450,000 to 1,000,000 Da have been observed.(Ref. 3007)
Synthesis
The primary site of synthesis of Lp (a) appears to be the hepatocyte, although apo (a) mRNA has also been identified in testes and brain.(Ref. 3008) Synthesis of apo (a) in liver is hardly surprising given that the hepatocyte is also the primary site of the synthesis of apo B-100.
METABOLISM
Metabolism
Lp(a) contains an LDL component having an apo B-100 moiety, early studies addressed the access of Lp (a) to LDL receptor pathways. Several groups have demonstrated that Lp (a) binds to the classic LDL receptor in cultured fibroblasts, although with a lower affinity than LDL itself; the estimated apparent Kd for Lp (a) is 9.5 nM compared with 7.8 nM for LDL, according to Krempler and colleagues.
GENETIC INFORMATION
The cDNA for apo (a) predicted a protein consisting of tandemly repeated plasminogen kringle-four-like domains followed by a single plasminogen kringle-five-like and protease domain. It is postulated that the differences in the sizes of the isoforms is a result of allelic variation in the number of kringle-four repeats. The apo (a) gene has been localized to the long arm of chromosome 6 (q26-27) where it is closely linked to the plasminogen gene.(Ref. 3012)
NOTE

REFERENCES
[3001]
AUTHOR:Scanu, A. M.
TITLE:Lipoprotein(a). A genetic risk factor for premature coronary heart disease PubMed ID:1534588
JOURNAL:Jama.
VOL:267 PAGE : 3326-3329 (1992)
[TOP]

[3002]
AUTHOR:Sattler, W., Kostner, G. M., Waeg, G., and Esterbauer, H.
TITLE:Oxidation of lipoprotein Lp(a). A comparison with low-density lipoproteins PubMed ID:1825020
JOURNAL:Biochim Biophys Acta.
VOL:1081 PAGE : 65-74 (1991)
[TOP]

[3003]
AUTHOR:Gaubatz, J. W., Heideman, C., Gotto, A. M., Jr., Morrisett, J. D., and Dahlen, G. H.
TITLE:Human plasma lipoprotein [a]. Structural properties PubMed ID:6220008
JOURNAL:J Biol Chem.
VOL:258 PAGE : 4582-4589 (1983)
[TOP]

[3004]
AUTHOR:AD, M. Bewu, and Durrington, P. N.
TITLE:Lipoprotein (a): structure, properties and possible involvement in thrombogenesis and atherogenesis PubMed ID:2149271
JOURNAL:Atherosclerosis.
VOL:85 PAGE : 1-14 (1990)
[TOP]

[3005]
AUTHOR:Armstrong, V. W., Walli, A. K., and Seidel, D.
TITLE:Isolation, characterization, and uptake in human fibroblasts of an apo(a)-free lipoprotein obtained on reduction of lipoprotein(a) PubMed ID:2999280
JOURNAL:J Lipid Res.
VOL:26 PAGE : 1314-1323 (1985)
[TOP]

[3006]
AUTHOR:Berg, K.
TITLE:A New Serum Type System In Man--The Lp System PubMed ID:14064818
JOURNAL:Acta Pathol Microbiol Scand.
VOL:59 PAGE : 369-382 (1963)
[TOP]

[3007]
AUTHOR:McLean, J. W., Tomlinson, J. E., Kuang, W. J., Eaton, D. L., Chen, E. Y., Fless, G. M., Scanu, A. M., and Lawn, R. M.
TITLE:cDNA sequence of human apolipoprotein(a) is homologous to plasminogen PubMed ID:3670400
JOURNAL:Nature.
VOL:330 PAGE : 132-137 (1987)
[TOP]

[3008]
AUTHOR:Tomlinson, J. E., McLean, J. W., and Lawn, R. M.
TITLE:Rhesus monkey apolipoprotein(a). Sequence, evolution, and sites of synthesis PubMed ID:2925643
JOURNAL:J Biol Chem.
VOL:264 PAGE : 5957-5965 (1989)
[TOP]

[3009]
AUTHOR:Dahlen, G. H., Guyton, J. R., Attar, M., Farmer, J. A., Kautz, J. A., and Gotto, A. M., Jr.
TITLE:Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography PubMed ID:2944670
JOURNAL:Circulation.
VOL:74 PAGE : 758-765 (1986)
[TOP]

[3010]
AUTHOR:Armstrong, V. W., Cremer, P., Eberle, E., Manke, A., Schulze, F., Wieland, H., Kreuzer, H., and Seidel, D.
TITLE:The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels PubMed ID:2948513
JOURNAL:Atherosclerosis.
VOL:62 PAGE : 249-257 (1986)
[TOP]

[3011]
AUTHOR:Frick, M. H., Dahlen, G., Berg, K., Valle, M., and Hekali, P.
TITLE:Serum lipids in angiographically assessed coronary atherosclerosis PubMed ID:202436
JOURNAL:Chest.
VOL:73 PAGE : 62-65 (1978)
[TOP]

[3012]
AUTHOR:Drayna, D. T., Hegele, R. A., Hass, P. E., Emi, M., Wu, L. L., Eaton, D. L., Lawn, R. M., Williams, R. R., White, R. L., and Lalouel, J. M.
TITLE:Genetic linkage between lipoprotein(a) phenotype and a DNA polymorphism in the plasminogen gene PubMed ID:2976021
JOURNAL:Genomics.
VOL:3 PAGE : 230-236 (1988)
[TOP]

Last updated June 19, 2007. Copyright © 1989-2007 Japanese Conference on the Biochemistry of Lipids (JCBL). All rights reserved.