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Biomedical subjects

G C Chen

Publications and source records attributed to G C Chen.

At least 73 records · Page 4Linked to original sources

beta-Carotene as a probe of lipid domains of reconstituted human plasma low-density lipoprotein: induced circular dichroism.

Mixtures of neutral lipids containing cholesteryl esters and beta-carotene were used to reconstitute the lipid core of heptane-extracted low-density lipoproteins (LDL). The resulting preparations of reconstituted LDL, referred to as r-[cholesteryl ester + beta-carotene]LDL, exhibited temperature-dependent circular dichroism (CD) in the visible region similar to that of native LDL. Since beta-carotene lacks intrinsic optical asymmetry, the observed CD must be induced by environmental constraint. LDL reconstituted with cholesteryl oleate, cholesteryl linoleate, or cholesteryl linolenate in the presence of beta-carotene exhibited thermotropic transitions at approximately 40, 35, and 30 degrees C, respectively. These temperatures are similar to the liquid-crystalline to isotropic liquid phase transition temperatures observed for pure cholesteryl ester model systems. The addition of triolein to r-[cholesteryl linoleate + beta-carotene]LDL lowered the transition temperature and decreased the specific ellipticity of the visible CD bands. When triolein accounted for 70% or more of the total neutral lipid content of r-[cholesteryl linoleate + triolein + beta-carotene]LDL, specific ellipticity was zero. The addition of low levels of unesterified cholesterol to r-[cholesteryl linoleate + beta-carotene]LDL did not alter the transition temperature but did reduce the specific ellipticity by 40%. The current data indicate that the organization of the core of neutral lipids in reconstituted LDL resembles that of native LDL with respect to environmental constraint on the beta-carotene molecule and that the helicity of the protein moiety resembles that of native LDL. In addition, the data are consistent with the possibility that the core cholesteryl esters of reconstituted LDL undergo phase transitions similar to their transitions in the free state.

Absorption↗

Radioimmunoassay of human arginine-rich apolipoprotein, apoprotein E. Concentration in blood plasma and lipoproteins as affected by apoprotein E-3 deficiency.

A radioimmunoassay for apolipoprotein E in human blood serum has been developed that measures equally the major polymorphic species of the protein (apolipoproteins E-1, E-2, E-3, and E-4) and the apo E in the dimer of apolipoproteins E and A-II. The assay is specific and yields values for apolipoprotein E in very low density lipoproteins that agree closely with those obtained by a quantitative electrophoretic method. Apolipoprotein E is also present in at least one species of high density lipoprotein, but the content of apolipoprotein E in the lipoprotein fractions of plasma is uncertain owing to dissociation during ultracentrifugation. The concentration of apolipoprotein E is higher in serum of normolipidemic, premenopausal women than in men of comparable age and is a direct function of the serum triglyceride level. Apolipoprotein E levels are increased out of proportion to triglyceride levels in hyperlipidemic patients with familial dysbetalipoproteinemia (homozygotes for lack of apolipoprotein E-3). Heterozygous relatives of homozygotes have significantly higher apolipoprotein E levels in serum than unaffected relatives. The concentration of partially degraded (remnant) triglyceride-rich lipoproteins also appears to be increased in heterozygotes, who comprise about 15% of the population.

Amino Acids↗

Secondary structure in very low density and intermediate density lipoproteins of human serum.

We have studies the secondary structures of the protein moieties of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) of human serum by circular dichroism (CD). Two potential complications in the application of this technique to lipoproteins have been evaluated. First, using chronographic potentiometry in CD measurements of VLDL fractions of different mean particle diameters, we have analyzed statistically the CD signals in order to define the limits imposed by light scattering with respect to both particle diameter and wavelength. We found that CD measurements can be made to as low as 210 nm on particles of 520 A or smaller, and to 194 nm on particles of 450 A and below. Second, we have evaluated the CD contribution of lipid chromophores. Despite the high ratio of lipid to protein, the relative CD effect of the lipids is smaller than for low density lipoproteins (LDL). due to the extremely small ellipticity of natural VLDL triglycerides. Thus, CD measurements can be obtained with confidence on the preponderant bulk of normal VLDL. For the first time we report the CD spectra of human VLDL and IDL. In contrast with human LDL and the lipoproteins of the hypercholesterolemic rabbit, the entire CD SPECTRUM OF HUMAN VLDL shows increased ellipticity with decreasing temperature, which is completely reversible. We have found that the protein moieties of human VLDL and IDL contain substantially more helix (approximately 50%) than does that of human LDL.

Animals↗

Confirmation of regional assignment of nucleoside phosphorylase (NP) on chromosome 14 by gene dosage studies.

Gene dosage studies yielded results consistent with assignment of the locus for nucleoside phosphorylase to band 14q13. The red blood cells from a patient with the karyotype 47,XX,+der(14),t(8;14)(8qter leads to 8q24::14q21 leads to 14pter)pat had enzyme activity 50% higher than red cells from 47 normal controls, two trisomies involving chromosomes other than 14, and five balanced translocations involving chromosome 14. On the other hand, the red cells of a case with a karyotype 45,XX,-14,-22+der(22),t(14;22)(14qter leads to 14q11 or 14q12::22p11 leads to 22qter)mat and a case with a a karyotype 47,XX,+der(14),t(14;16)(14pter leads to 14q11::16q24 leads to 16qter)mat had normal activity

Child, Preschool↗

Conformation of beta-endorphin and beta-lipotropin: formation of helical structure in methanol and sodium dodecyl sulfate solutions.

Circular dichroic spectra of camel beta-endorphin and ovine beta-lipotropin in water show little, if any, secondary structure. Intrinsic viscosities and sedimentation coefficients of the two peptides also suggest that the molecules are not compact and globular. Methanol or sodium dodecyl sulfate promotes the formation of helical structure to an extent as much as one-half of either peptide molecule. The conformation of the complex between camel beta-endorphin and dodecyl sulfate may be related to the opiate-like function of this peptide hormone.

Amino Acid Sequence↗

Temperature dependence of the optical activity of human serum low density lipoprotein. The role of lipids.

Low density lipoprotein (LDL) (1.024-1.045 G/cm3) was prepared by ultracentrifugal flotation from serum of normal fasting subjects. Circular dichroism (CD) and optical rotatory dispersion (ORD) spectra in the ultraviolet region were measured at 2, 25, and 37 degrees on LDL, lipid extracted from LDL, and on pure component lipids. All exhibit reversible, temperature-dependent optical activities. Sphingomyelin has a strong negative CD band around 195 nm. Cholesterol and cholesteryl esters have a CD minimum at 208 nm. They have positive CD bands around 201 and 198 nm which decrease sharply and become negative at 198 and 193 nm, respectively. The CD of the total lipid extract of LDL is negative and drops monotonically below 200 nm. Thus, the lipid moiety could account for the increasing negativity of the CD of LDL below 195 nm. After subtraction of the ellipticity corresponding to amounts of lipids in organic solvents equivalent to those found in LDL, the 208-210 nm trough of LDL diminishes markedly. This is accompanied by a blue-shift of the extrema from 195-196 to 193 nm and an increase in the magnitude of the positive ellipticity. The fractions of helix and of beta form in the protein, determined by the method of Y. H. Chen, J. T. Yang, and K. H. Chau ((1974), Biochemistry 13, 3350), in the wavelength interval of 250-240 nm, remain essentially unchanged between 2 and 37 degrees. These observations suggest that a substantial part of the thermal change in the CD spectrum of LDL between 208 and 210 nm may be attributable to lipids.

Cholesterol↗

6-Thio and -seleno-beTa-D-glucose esters of dimethylarsinous acid.

Syntheses of 2-Se-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranosyl)-3-N,N-dimethylselenopseudourea hydroiodide (3), 1,2,3,4-tetra-O-acetyl-6-S-dimethylarsino-6-thio-beta-D-glucopyranose (4), 1,2,3,4-tetra-O-acetyl-6-Se-dimethylarsino-6-seleno-beta-D-glucopyranose (7), 6-S-dimethylarsino-6-thio-beta-D-glucopyranose (5), and 6-Se-dimethylarsino-6-seleno-beta-D-glucopyranose (9) are described. Various spectral properties of the compounds are given. The relative rates of alkaline hydrolysis of 5 and 9 are compared.

Arsenicals↗