Leland L. Smith

Biological activities of oxysterols

Literature dealing with the biological activities of cholesterol autoxidation products and related oxysterols in vivo and in vitro published since the previous 1981 monograph is reviewed. Although several oxysterols are important cholesterol metabolites implicated in bile acids and steroid hormones biosynthesis, effects on cellular membranes and on specific enzyme systems as well as cytotoxic, atherogenic, mutagenic, and carcinogenic activities characterize oxysterols as a class. Circumstantial evidence implicates oxysterols of the human diet and those formed in vivo with human health disorders, but recent work also supports an hypothesis that some oxysterols be endogenous intracellular regulators of de novo sterol biosynthesis. The true physiological relevance, if any, of these matters has not been adduced.

Cholesterol autoxidation 1981–1986

Literature published between 1980 and 1986 dealing broadly with the topic of cholesterol autoxidation is reviewed. The review builds on the detailed 1981 monographic treatment of the topic by the author and covers new items of chemistry, analysis, and metabolism.

REVIEW OF PROGRESS IN STEROL OXIDATIONS : 1987-1995

Material dealing with the chemistry, biochemistry, and biological activities of oxysterols is reviewed for the period 1987–1995. Particular attention is paid to the presence of oxysterols in tissues and foods and to their physiological relevance.

Thin-layer chromatographic examination of cholesterol autoxidation

Abstract The air oxidation of cholesterol has been studied by means of one- and two-dimensional thin-layer chromatographic methods herein developed; A semi-quantitative photoelectric densitometric procedure for evaluation of one-dimensional chromatoplates is also described. The autoxidation ofcholesterol by heating or storing in air, irradiation in air, treatment with benzoyl peroxide, purification via the dibromide, and in sodium stearate colloidally dispersed medium has been examined and the autoxidation products resolved by thin-layer chromatography have been catalogued. The complexity of the air oxidation of cholesterol is emphasized as is the necessity of careful control work in chemical and biological systems containing cholesterol.

Another cholesterol hypothesis: cholesterol as antioxidant

Current emphasis on cholesterol as agency if not cause of human atherosclerosis and subsequent cardiovascular disease ignores the essentiality of cholesterol in life processes. Additionally ignored is the ubiquitous presence of low levels of oxidized cholesterol derivatives (oxysterols) in human blood and select tissues, oxysterols also implicated in atherosclerosis. Whereas such oxysterols may be regarded putatively as agents injurious to the aorta, an alternative view of some of them is here proposed: that B-ring oxidized oxysterols of human blood represent past interception of blood and tissue oxidants in vivo by cholesterol as an ordinary aspect of oxygen metabolism. Such interception and subsequent efficient hepatic metabolism of oxysterols so formed, with biliary secretion and fecal excretion, constitute as in vivo antioxidant system. Whether cholesterol, oxysterols, oxidized lipoproteins, or oxidants in blood, singly or in concert, cause or exacerbate human atherosclerosis remains to be understood.

Detection of sterol hydroperoxides on thin-layer chromatoplates by means of the wurster dyes

Abstract A specific and sensitive means of detection of sterol hydroperoxides on irrigated thin-layer chromatoplates using N,N-dimethyl-p-phenylenediamine dihydrochloride or N,N,N′,N′-tetramethyl-p-phenylenediamine dihydrochloride has been developed. Using the color test the presence of specific sterol hydroperoxides in aged samples of cholesterol, stigmasterol, β-sitosterol, lanosterol, 24,25-dihydrolanosterol, 3α, 5-cyclo-5α-cholestan-6β-ol, 5α-cholest-7-en-3β-ol, and 5α-cholest-8(14)-en-3β-ol and the absence of sterol hydroperoxides in similarly stored samples of 5α-cholestan-3β-ol and 5β-cholestan-3β-ol are demonstrated. Autoxidation of cholesterol in the solid state, in the irradiated solid state, in colloidal dispersion, and in aerated solution is shown to proceed via initial formation of sterol hydroperoxides.

High-performance liquid chromatography of cholesterol autoxidation products

Abstract High-performance liquid chromatography with microparticulate silica gel and octadecyl silica reversed-phase columns accords ready resolution of the common autoxidation products of cholesterol. Resolution of two pairs of isomeric sterols (5,6α-epoxy-5α-cholestan-3β-ol and 5,6β-epoxy-5β-cholestan-3β-ol, 3β-hydroxy-5α-cholest-6-ene-5-hydroperoxide and 3β-hydroxycholest-5-ene-7α-hydroperoxide) not previously resolved chromatographically has been achieved in both systems. Application of the procedure to the isolation of cholesta-4,6-dien-3-one from autoxidized cholesterol is described.

Sterol metabolism—XLVII. oxidized cholesterol esters in human tissues☆

Abstract Human aorta, liver, and plasma have been examined for the presence of fatty acylesters of oxidized cholesterol derivatives using high performance liquid chromatography and chemical ionization mass spectrometry. Many such sterol esters have been detected, including eight individual diesters and six individual monoesters of six sterols and six C 14 -C 18 fatty acids. Mono- and di-esters of the epimeric 5-cholestene-3β,7-diols, 5-cholestene-3β,25-diol, and a 5-cholestene-3β,26-diol were found at μ/g levels in aorta; palmitate esters of 5-cholestene-3β,25-diol and 3β-hydroxy-5-cholesten-7-one were detected at ng/g levels in liver; and esterified 5-cholestene-3β,7α-diol,5-cholestene-3β,7β-diol, 3β-hydroxy-5-choles ten-7-one, a 5-cholestene-3β.24-diol, 5-cholestene-3β,25-diol, and a 5-cholestene-3β,26-diol were present in plasma at ng/ml levels. The presence of esterified 5-cholestene-3β,7α-diol, 5-cholestene-3β,7β-diol, and 3β-hydroxy-5-cholesten-7-one together may be interpreted as evidence of in vivo lipid peroxidation of cholesterol.

Biotransformations of Steroids

Different types of microbiological transformation of steroids are reviewed, with special attention given to bioconversions applied in the manufacturing of steroid hormones, i.e., 11 alpha- 11 beta-, 16 alpha-, 17 alpha-hydroxylations and 1-dehydrogenation. Availability and utilization of raw materials for industrial production of steroids of the estrane, androstane, and pregnane series are discussed. Among the current trends in steroid research of a practical nature, immobilization of enzymes and living cells and the spore process are emphasized as alternative techniques of steroid transformation of possible future importance. Efforts to recognize, in cell-free preparations, the components of steroid-transforming enzyme systems as well as the cellular mechanisms of control of their biosynthesis and activity are described in order to illustrate the main subjects of current basic investigation in steroid bioconversion.

Mutagenic cholesterol preparations

Naturally air-aged commercial samples of USP or reagent-grade cholesterol contain components which are mutagenic towards Salmonella typhimurium strains TA1537, TA1538 and TA98. These mutagenic components are associated with the polar cholesterol autoxidation products, but identity of the mutagenic components has not been achieved. Pure crystalline nonmutagenic cholestrol free from autoxidation products becomes mutagenic towards these strains upon heating at 70 degrees in air or following exposure to 60 Co gamma-radiation.