Showing papers on "Mevalonic acid published in 1997"

Medicinal Natural Products: A Biosynthetic Approach

Abstract: About this book and how to use it Secondary metabolism: The building blocks and construction mechanisms The acetate pathway: Fatty acids and polyketides The shikimate pathway: Aromatic amino acids and phenylpropanoids The mevalonate and deoxyxylulose phosphate pathways: Terpenoids and Steroids: Alkaloids Peptides, proteins and other amino acid derivatives Carbohydrates Index

Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages.

Abstract: This study explores the role of mevalonate inhibitors in the activation of NF-kbeta and the induction of inducible nitric oxide synthase (iNOS) and cytokines (TNF-alpha, IL-1beta, and IL-6) in rat primary astrocytes, microglia, and macrophages Lovastatin and sodium phenylacetate (NaPA) were found to inhibit LPS- and cytokine-mediated production of NO and expression of iNOS in rat primary astrocytes; this inhibition was not due to depletion of end products of mevalonate pathway (eg, cholesterol and ubiquinone) Reversal of the inhibitory effect of lovastatin on LPS-induced iNOS expression by mevalonate and farnesyl pyrophosphate and reversal of the inhibitory effect of NaPA on LPS-induced iNOS expression by farnesyl pyrophosphate, however, suggests a role of farnesylation in the LPS-mediated induction of iNOS The inhibition of LPS-mediated induction of iNOS by FPT inhibitor II, an inhibitor of Ras farnesyl protein transferase, suggests that farnesylation of p21(ras) or other proteins regulates the induction of iNOS Inhibition of LPS-mediated activation of NF-kbeta by lovastatin, NaPA, and FPT inhibitor II in astrocytes indicates that the observed inhibition of iNOS expression is mediated via inhibition of NF-kbeta activation In addition to iNOS, lovastatin and NaPA also inhibited LPS-induced expression of TNF-alpha, IL-1beta, and IL-6 in rat primary astrocytes, microglia, and macrophages This study delineates a novel role of the mevalonate pathway in controlling the expression of iNOS and different cytokines in rat astrocytes, microglia, and macrophages that may be important in developing therapeutics against cytokine- and NO-mediated neurodegenerative diseases

Two independent biochemical pathways for isopentenyl diphosphate and isoprenoid biosynthesis in higher plants

Abstract: In the early times of isoprenoid research, a single pathway was found for the formation of the C5 monomer, isopentenyl diphosphate (IPP), and this acetate/mevalonate pathway was supposed to occur ubiquitously in all living organisms. Now, 40 years later, a totally different IPP biosynthesis route has been detected in eubacteria, green algae and higher plants. In this new pathway glyceraldehyde 3-phosphate (GAP) and pyruvate are precursors of isopentenyl diphosphate, but not acetyl-CoA and mevalonic acid. In green tissues of three higher plants it was shown that all chloroplastbound isoprenoids (β-carotene, phytyl chains of chlorophylls and nona-prenyl chain of plastoquinone-9) are formed via the GAP/pyruvate pathway, whereas the cytoplasmic sterols are formed via the acetate/mevalonate pathway. Also, isoprene, emitted by various plants at high light conditions by action of the plastid-bound isoprene synthase, is formed via the new GAP/pyruvate pathway. Thus, in higher plants, there exist two separate and biochemically different IPP biosynthesis pathways: (1) the novel alternative GAP/pyruvate pathway apparently bound to the plastidic compartment and (2) the classical cytoplasmic acetate/mevalonate pathway. This new GAP/pyruvate pathway for IPP formation allows a reasonable interpretation of previous odd results concerning the biosynthesis of chloroplast isoprenoids, which, so far, had mainly been interpreted assuming compartmentation differences. The novel GAP/pyruvate pathway for IPP formation in plastids appears as a heritage of their prokaryotic, endosymbiotic ancestors.

Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis

Abstract: We examined the effect of fluvastatin, the first entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that is structurally different from other vastatins, on tissue factor (TF) expression in human macrophages spontaneously differentiated in culture from blood monocytes. Fluvastatin decreased TF activity in a dose-dependent manner (1 to 5 mumol/L) in both unstimulated and lipopolysaccharide-stimulated macrophages, and this reduction paralleled the decrease in immunologically recognized TF protein. The same results were obtained with another lipophilic vastatin, simvastatin, but not with hydrophilic pravastatin. The reduction in TF expression was also observed in macrophages enriched in cholesterol after exposure to 50 micrograms/mL acetylated low density lipoprotein. The inhibitory effect of fluvastatin on TF activity and antigen was fully reversible by coincubation with 100 mumol/L mevalonate or 10 mumol/L all-trans-geranylgeraniol but not with dolichol, farnesol, or geraniol. Suppression of TF antigen and activity was accompanied by a diminution in TF mRNA levels, which was completely prevented by mevalonate. Furthermore, fluvastatin impaired bacterial lipopolysaccharide-induced binding of c-Rel/p65 heterodimers to a kappa B site in the TF promoter, indicating that this drug influences induction of the TF gene. We conclude that lipophilic vastatins inhibit TF expression in macrophages, and because this effect is prevented by mevalonate and geranylgeraniol, a geranylgeranylated protein plays a crucial role in the regulation of TF biosynthesis. The suppression of TF in macrophages by vastatins indicates a potential mechanism by which these drugs interfere with the formation and progression of atherosclerotic plaque as well as thrombotic events in hyperlipidemic patients.

The orphan nuclear receptor LXRalpha is positively and negatively regulated by distinct products of mevalonate metabolism

Abstract: LXRα is an orphan member of the nuclear hormone receptor superfamily that displays constitutive transcriptional activity. We reasoned that this activity may result from the production of an endogenous activator that is a component of intermediary metabolism. The use of metabolic inhibitors revealed that mevalonic acid biosynthesis is required for LXRα activity. Mevalonic acid is a common metabolite used by virtually all eukaryotic cells. It serves as a precursor to a large number of important molecules including farnesyl pyrophosphate, geranylgeranyl pyrophosphate, cholesterol, and oxysterols. Inhibition of LXRα could be reversed by addition of mevalonic acid and certain oxysterols but not by other products of mevalonic acid metabolism. Surprisingly, the constitutive activity of LXRα was inhibited by geranylgeraniol, a metabolite of mevalonic acid. These findings suggest that LXRα may represent a central component of a signaling pathway that is both positively and negatively regulated by multiple products of mevalonate metabolism.

Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase

Abstract: Regulation of the sterol-synthesizing mevalonate pathway occurs in part through feedback-regulated endoplasmic reticulum degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R). In yeast, the Hmg2p isozyme of HMG-R is regulated in this manner. We have tested the involvement of ubiquitination in the regulated degradation of Hmg2p, by using both genetic and direct biochemical approaches. Hmg2p degradation required the UBC7 gene, and Hmg2p protein was directly ubiquitinated. Hmg2p ubiquitination was dependent on UBC7 and was specific for the degraded yeast Hmg2p isozyme. Furthermore, Hmg2p ubiquitination was regulated by the mevalonate pathway in a manner consistent with regulation of Hmg2p stability. Thus, regulated ubiquitination appeared to be the mechanism by which Hmg2p stability is controlled in yeast. Finally, our data indicated that the feedback signal controlling Hmg2p ubiquitination and degradation was derived from farnesyl diphosphate, and thus implied conservation of an HMG-R degradation signal between yeast and mammals.

Mevalonate-Dependent Inhibition of Transendothelial Migration and Chemotaxis of Human Peripheral Blood Neutrophils by Pravastatin

Abstract: Pravastatin, a hydrophilic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, has been reported to beneficially affect atherogenesis, plaque stability, and transient myocardial ischemia in significant coronary artery disease by influencing lipid metabolism and by intracellular signaling via mevalonate pathway products other than cholesterol. Leukocytes are implicated to play a pathophysiological role in these events. We were interested in finding out whether pravastatin could affect transendothelial migration (TEM), chemotaxis, and respiratory burst activity of the neutrophil ex vivo. In addition, effects on monocyte and T-lymphocyte chemotaxis were tested. For TEM assays, monolayers of human umbilical vein endothelial cells (HUVECs) were grown to confluence on polycarbonate filters bearing 5-microns pores in Transwell (Costar) culture plate inserts. Chemotaxis experiments were performed using modified Boyden chambers with cellulose nitrate micropore filters. Respiratory burst activity was measured fluorometrically. Treatment of neutrophils and monocytes with pravastatin at 2 to 200 mumol/L and 10 to 1000 mumol/L, respectively, significantly decreased chemotaxis triggered by fMet-Leu-Phe. This effect was abolished in the presence of mevalonic acid (500 mumol/L); no effect of pravastatin was seen on T-lymphocyte chemotaxis triggered by interleukin-8. Preincubation of neutrophils with pravastatin (200 mumol/L) also resulted in a significant reduction in the number of neutrophils that transmigrated a tumor necrosis factor-stimulated or lipopolysaccharide-stimulated HUVEC monolayer. At none of the concentrations tested (2 pmol/L to 200 mumol/L) did pravastatin affect neutrophil respiratory burst activity. We conclude that pravastatin may alter monocyte chemotaxis and neutrophil-endothelial interactions in migratory responses at concentrations obtained in vivo with cholesterol-lowering doses.

Biosynthesis of the labdane diterpene marrubiin in Marrubium vulgare via a non-mevalonate pathway.

Abstract: The biosynthesis of the furanic labdane diterpene marrubiin has been studied in plantlets and shoot cultures of Marrubium vulgare (Lamiaceae). The use of [2-14C]acetate, [2-14C]pyruvate, [2-14C]mevalonic acid and [U-14C]glucose incorporation experiments showed that the labelling of sterols in etiolated shoot cultures of M. vulgare was in accordance with their biosynthesis via the acetate-mevalonate pathway. In contrast, the incorporation rates of these precursors into the diterpene marrubiin could not be explained by biosynthesis of this compound via the acetate-mevalonate pathway. Cultivation of etiolated shoot cultures of M. vulgare on medium containing [1-13C]glucose and subsequent 13C-NMR spectroscopy of marrubiin led to the conclusion that the biosynthesis of marrubiin follows a non-mevalonate pathway. All isoprenic units of 13C-labelled marrubiin were enriched in those carbons that correspond to positions 1 and 5 of a putative precursor isopentenyl diphosphate. This labelling pattern from [1-13C]glucose is consistent with an alternative pathway via trioses, which has already been shown to occur in Eubacteria and Gymnospermae. The labdane skeleton is a precursor of many other skeletal types of diterpenes. Therefore it becomes obvious that in connection with the few known examples of a non-mevalonate pathway to isoprenoids the formation of some isoprenoids in plants via a non-mevalonate pathway might be quite common.

Natural Product Chemistry: A mechanistic, biosynthetic and ecological approach

Abstract: Chemical ecology carbohydrates and primary metabolites the shikimic acid pathway the polyketide pathway the mevalonic acid pathway the terpenes amino acids, peptides and proteins the alkaloids N-hetroaromatics answers to problems.

Light modulates the spatial patterns of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in Arabidopsis thaliana.

Abstract: Summary Although the coordinated biosynthesis of isoprenoid compounds is thought to be essential to the normal processes of plant growth and development, the mechanisms that regulate the mevalonate pathway in plants are not well understood. As the first committed step in the pathway, the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonic acid by HMG CoA reductase and the regulation of the genes encoding this enzyme have been implicated in the network that controls isoprenoid biosynthesis in higher plants. Using histochemical staining for β-glucuronidase, as well as conventional RNA hybridization analysis, the temporal and spatial regulation of HMG1, one of the genes encoding HMG CoA reductase in the crucifer Arabidopsis thaliana, has been characterized. Furthermore, the HMG1 promoter is shown to be differentially responsive to illumination in different organs, and promoter activation by light deprivation is confined primarily to immature leaves. In contrast, expression of the HMG1 gene in roots is confined to the elongation zone and is not responsive to illumination. Light-mediated regulation of HMG1 expression is shown to be an organ-autonomous response that depends on direct illumination, and environmental cues regarding light do not appear to be exchanged between different organs in Arabidopsis. These studies reveal several new features of HMG1 regulation, and indicate that the high levels of HMG CoA reductase expression detected in immature leaves may be primarily attributed to the dark-induced expression of HMG1, and that HMG1 is expressed at low levels throughout the plant in response to light. Thus, environmental cues interact with the developmental program to define the pattern of HMG1 gene expression in Arabidopsis.

In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells

Abstract: We analyzed the antiproliferative effect of simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on human glioma cell lines. Inhibition of cell growth with SV was observed in all cell lines tested. Different culture conditions altered this inhibition of growth: the lower the concentration of fetal bovine serum (FBS) in the medium, the higher the inhibitory effect of SV on glioma cells. On morphological examination, we found that most of the cells exposed to SV became rounded and the proportion of floating cells was increased in a time-dependent manner. Then we examined whether exogenously added mevalonic acid reversed the growth inhibitory effect of SV. Exogenous mevalonic acid suppressed the inhibitory effect of SV on glioma cells in a dose-dependent manner. SV also enhanced the expression of low-density lipoprotein (LDL) receptor on glioma cells. We also found that peroxidized LDL (p-LDL) was cytotoxic to glioma cells and that SV had additive effects on pLDL-induced cytotoxicity. In a mouse model, growth of glioma cells inoculated into nude mice was inhibited by intratumoral injection of both SV and peroxidized LDL. These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for the growth of glioma cells and that simvastatin and/or peroxidized LDL should be examined further as potential therapeutic agents for gliomas.

The saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential for viability, and a single leu-to-pro mutation in a conserved sequence leads to thermosensitivity

Abstract: The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. We used the Saccharomyces cerevisiae temperature-sensitive mutant defective for mevalonate diphosphate decarboxylase previously described (C. Chambon, V. Ladeveve, M. Servouse, L. Blanchard, C. Javelot, B. Vladescu, and F. Karst, Lipids 26:633-636, 1991) to characterize the mutated allele. We showed that a single change in a conserved amino acid accounts for the temperature-sensitive phenotype of the mutant. Complementation experiments were done both in the erg19-mutated background and in a strain in which the ERG19 gene, which was shown to be an essential gene for yeast, was disrupted. Epitope tagging of the wild-type mevalonate diphosphate decarboxylase allowed us to isolate the enzyme in an active form by a versatile one-step immunoprecipitation procedure. Furthermore, during the course of this study, we observed that a high level of expression of the wild-type ERG19 gene led to a lower sterol steady-state accumulation compared to that of a wild-type strain, suggesting that this enzyme may be a key enzyme in mevalonate pathway regulation.

Cholesterol metabolism and tumor cell proliferation.

Abstract: The functions assumed by free cholesterol in mammalian cells are diverse, ranging from that as a starting substrate for the synthesis of steroid hormones and bile salts to its less specifically understood but critical role as a principal lipid component of every cell membrane. Cholesterol biosynthesis begins with metabolically supplied cytoplasmic acetyl CoA that also serves as the common precursor for de novo fatty acid synthesis, and can be expressed by the reaction: 18 acetyl CoA + 1/2O2 + 10 H+ → cholesterol + 9 CO2 +18 CoA-SH. During the synthesis, the genesis of mevalonic acid (MVA) from 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), catalyzed by HMG-CoA reductase (HMGR), the third and principal rate-controlling enzyme of the pathway, leads to the production of diverse polyisoprenoid intermediates. Metabolism of MVA demonstrates considerable versatility through ensuing branching reactions that yield a host of terpene compounds used in the construction of an assortment of required metabolites [dolichol, ubiquinone(Coenzyme Q), isopentenyl adenine, heme a/a3], in addition to cholesterol itself. This chapter focuses on associations that link cholesterol and mitochondrial citrate export, as well as the metabolism of citrate-derived isoprenoid metabolites en route to cholesterol synthesis, with deregulated cell proliferation (i.e., cancer).

Different points of action of retinoids and anti-estrogens in G1 phase identified in synchronized T-47D breast cancer cells.

Abstract: Both retinoids and anti-estrogens inhibit breast cancer cell proliferation with accumulation of cells in the G 1 Phase of the cell cycle, but the effect of retinoids is delayed compared to that of anti-estrogens. To determine whether this temporal difference is due to a simple delay in the action of retinoids on a common site or to different sites of action within the G 1 phase, we studied the cell cycle effects of retinoic acid (RA) and the anti-estrogen ICI 164384 (ICI) in T-47D cells partially synchronized by mevalonic acid rescue of lovastatin-induced cell cycle arrest. We found that cells entering the cell cycle semi-synchronously after mevalonic acid rescue of lovastatin treatment were immediately susceptible to ICI but not RA. This suggests that RA may act at a point up-stream and ICI at a point down-stream of lovastatin action. Consistent with this, cells recommencing cell cycle progression after RA treatment were susceptible to the effects of lovastatin, while cells pre-treated with ICI then rescued with estradiol were not. In addition, cells rescued from cell cycle arrest induced by either RA, ICI or lovastatin entered S phase with the same kinetics. Our findings suggest, first, that within G 1 , RA acts before and ICI acts after the point of lovastatin action and, second, that despite these differences in the initiation of cell cycle arrest, the final nature of the cell cycle arrest is similar. Hence, retinoids and anti-estrogens may be expected to target different cell cycle-regulatory molecules to initiate cell cycle arrest, while overcoming this arrest may be accomplished by the activation of a common molecular pathway.

Mevalonate kinase deficiency in a dizygotic twin with mild mevalonic aciduria.

Abstract: Mevalonic aciduria, the result of mevalonate kinase (MKase) deficiency (McKusick 251170), is a rare abnormality of cholesterol and nonsterol isoprene biosynthesis identified in approximately 14 patients. The phenotype includes developmental delays, failure to thrive, hypotonia, ataxia, organomegaly, dysmorphia, cataracts, lymphadenopathy, myopathy and fat malabsorptive enteropathy. Many patients have recurrent febrile crises, accompanied by vomiting, diarrhoea, elevated white cell count and erythrocyte sedimentation rates, as well as arthralgia, oedema and morbilliform rash (Hoffmann et al 1993). Recently identified patients show evidence of ineffective erythropoiesis (K.M. Gibson, unpublished data). Despite considerable phenotypic variation, urinary excretion of mevalonic acid has been consistently and massively elevated at 0.9-56 mol/mol creatinine (normal < 0.003 mol/mol), without other metabolic abnormalities. MKase activity has been undetectable in extracts of peripheral or cultured cells derived from all patients (Hoffmann et al 1991). In the current report, we describe a newborn whose increased mevalonic acid concentrations in urine and plasma were considerably lower than levels detected in other patients. The excretion pattern correlated with a mild clinical course and a significant residual activity of MKase in peripheral and cultured cells.

Optical measuring method for mevalonic acid

Abstract: Acid is added to a target sample such as urine, blood plasma or serum for converting mevalonic acid contained in the sample to lactone mevalonate, and the sample is irradiated with near infrared Raman excitation light, for determining mevalonic acid by measuring generated Raman scattered light. This method employs no mediatory reaction with simple pretreatment, requires no high-priced measuring apparatus, and can determine mevalonic acid in a short time.

Short-term effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor on cholesterol and bile acid synthesis in humans.

Abstract: Competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase improve hypercholesterolemia. However, reports about the effects of these agents on bile acid synthesis, the metabolic pathway of cholesterol, are conflicting. We studied the short-term effect of one of these agents, pravastatin, on bile acid synthesis. Six male volunteers were given 40 mg of pravastatin. Plasma mevalonate level (which reflects cholesterol synthesis) and 7α-hydroxy-4-cholesten-3-one level 9which reflects bile acid synthesis) were measured every 2 h for 8 h. These plasma levels were compared to those of the same volunteers without pravastatin. Plasma mevalonate level after 2 h was lower than control (3.0 ± 1.1 ng/ml vs. 6.7 ± 2.5, mean ±SD; P<0.05). This decrease continued for 8 h (2.5 ± 0.8 vs. 5.2 ± 1.5; P<0.05). On the other hand, plasma 7α-hydroxy-4-cholesten-3-one level did not change until after 6 h; then at 8 h it was lower than control (15.7 ± 11.8 ng/mL vs. 24.7 ± 16.9; P <0.05). According to three-way layout analysis of variance, mevalonate level was influenced by both pravastatin treatment (P<0.01) and time-course (P<0.01). On the other hand, the 7α-hydroxy-4-cholesten-3-one level was affected by both individual difference (P<0.01) and time course (P<0.01), but pravastatin treatment did not influence this compound. This indicates that bile acid synthesis was not influenced by pravastatin, although cholesterol synthesis was inhibited. The shortterm inhibition of cholesterol synthesis did not affect bile acid synthesis.

Optimization of the Culture Medium for Growth and the Kinetics of Lactate Fermentation by Pediococcus sp. ISK-1

Abstract: The growth of a newly isolated strain of Pediococcus sp., designated ISK-1, was very slow and the concentration of cells in the medium remained low. Fermentation with an initial 30 g/liter glucose required about 60 h. To stimulate fermentation, we attempted to optimize the medium by flask culture and jar fermentation tests. Mevalonic acid and mieki (soy bean hydrolyzate) stimulated fermentation and increased the rate of formation of DL-lactate. Kinetic analysis of the fermentation showed that mevalonic acid markedly increased the specific glucose consumption rate and the specific lactate production rate. Mieki and mevalonic acid had a synergistic effect, but the effect of mevalonic acid was different from that of mieki.

Ubiquinone synthesis by Pneumocystis carinii: incorporation of radiolabeled polyprenyl chain and benzoquinone ring precursors.

Abstract: SUMMARY Radiolabeled mevalonic acid was incroporated in vitro into Pneumocystis carinii ubiquinone homologs, CoQ9 and CoQ10, dermostrating the isoprenoid branch pathway forming the polyprenyl chain of ubiquinone is functional in the organism. Radiolabeled shikimic acid, tyrosine and p-hydroxybenzoic acid were also incorporzated into the two ubiquinone homologs, indicating that P. carnii also possesed the biological pathway for de novo synthesis of the CoQ benzoquinone ring.

A Novel Mevalonate-Independent Pathway for the Biosynthesis of Carotenoids, Phytol and Prenyl Chain of Plastoquinone-9 in Green Algae and Higher Plants

Abstract: The acetate/mevalonate pathway, which provides IPP, had been investigated in the 50’s and 60’s in detail, and the universal occurrence of this pathway in animal and plant isoprenoid biosynthesis was generally accepted. However, some observations conflicted with this pathway. The biosynthesis of plastidic isoprenoids of higher plants (carotenoids, chlorophylls, plastoquinone-9) was not inhibited by mevinolin, a highly specific inhibitor of mevalonate formation (1, 2). In order to test if the plastidic isoprenoids of algae and higher plants are formed via the acetate/mevalonate pathway or via a different pathway some 13C-labelling experiments were carried out with two green algae and the higher plant Lemna. Here we show that in all three cases carotenoids and the prenyl side chains of chlorophylls and plastoquinone-9 are labelled via a new, bacterial and mevalonate-independent pathway of IPP biosynthesis (3, 4, 5).

Biosynthesis of sterols in green algae (scenedesmus, chlorella) according to a novel, mevalonate-independent pathway

Abstract: The biosynthesis of isopentenyl pyrophosphate (IPP), the biological precursor of isoprenoid substances, is known as the acetate mevalonate pathway. In the latter pathway the condensation of three acetyl-CoA, followed by two reduction steps (HMGCoA reductase), yields mevalonic acid which is converted to IPP. In higher plants, the biosynthesis of sterols occurs via mevalonic acid (1) and can be inhibited by mevinolin, a highly specific inhibitor of mevalonate formation (2). In contrast, in several green algae we could not find any inhibition effect of mevinolin on growth and multiplication of cells. Some 13C-labelling experiments in the green alga Scenedesmus (3) showed that the main sterol components are synthesized via a novel mevalonate-independent glyceraldehyde phosphate/pyruvate pathway of IPP biosynthesis first found in some eubacteria (4, 5). Here we show that this also applies to Chlorella.