Tetrahymena pyriformis, sterol

The triterpenes, e.g. tetrahymanol, are larger in cross-section than cholesterol. A better intermolecular fit is restored with acyclic lipids which have a larger cross-section than do the n-acyl chains found in eucaryotes. Increased effective cross-sections can be achieved by the introduction of cis double bonds this is partly how Tetrahymena pyriformis adjusts the composition of its phosphoUpids in its sterol-free, tetrahymanol-containing state. Another way to obtain thicker lipids is to have branched chains. Whereas only n-acyl lipids have been reported in Tetrahymena and... 

It is interesting to note that the protozoan, Tetrahymena pyriformis, lacks the capacity of sterol biosynthesis, but has the ability to dealkylate phytosterols [173]. 

The resolution of synthetic presqualene and prephytoene alcohols via their etienic acid derivatives has been reported. This work confirmed that the active (-f-)-enantiomers in both series have the same absolute configuration [(li , 2/ , 3/ )]. It has been established, by use of Hn.m.r., that the proton (deuteron) introduced at C-3 during the cyclization of squalene to tetrahymanol by Tetrahymena pyriformis has the 3/8 configuration. Both antipodes of the trimethyldecalol (13) have been shown to be effective inhibitors of cholesterol biosynthesis in rat liver enzyme preparations and cultured mammalian cells. The accumulation of squalene 2,3-oxide and squalene 2,3 22,23-dioxide in the treated systems indicates that inhibition occurs at the cyclization stage. The inhibitor is metabolized to the diol (14). The results of other sterol inhibition... 

Many steps in sterol biosynthesis are stimulated by a sterol carrier protein. The identity of this protein is not known but its effect seems to be widespread. A rat liver carrier protein also affects adrenal and brain systems. Substitution by a carrier protein from Tetrahymena pyriformis gave partial stimulation with the rat liver preparation. The function of this molecule may be regulatory. At low levels of carrier protein, sterol biosynthesis is mainly via A -sterols, whereas at higher levels the 24,25-dihydro-derivatives are preferred. Apo-lipoprotein II (and to a lesser extent I) produce a similar effect. ... 

A few simple eukaryotic organisms can cyclize squalene but do not produce sterols. For example, Tetrahymena pyri-formis (a protozoan) produces tetrahymanol (14), a pentacyclic analog of lanosterol (15) (Fig. 23.1), from squalene. The mechanism of condensation of squalene (1) to tetrahymanol in Tetrahymena pyriformis does not involve squalene 2,3-oxide (2) and includes a protonation step, cyclization, and, finally, addition of hydroxyl group from the medium. The stereochemistry of the proton predicted to be incorporated at the 21p-position of the compound has been estab-... 

All these results taken together indicate that cyclopropylsterols can replace effectively A -sterols as membrane components in higher plants as well as in other organisms such as the GL7 yeast mutant (7), Mycoplasma capricolum (8) or Tetrahymena pyriformis (9). Further investigations are necessary to determine whether other sterol structures like A -sterols or A ,14a-methylsterols are also suitable for playing a similar role. 

Metabolism of Sterols. It is interesting that a heat-stable sterol carrier protein (SCP) has been detected in the protozoan Tetrahymena pyriformis. This protozoan-SCP (P-SCP) was required, in addition to oxygen and pyridine nucleotides, for conversion of cholesterol into cholesta-5,7,22-trien-3p-ol by the protozoan microsomal enzymes (A - and A -dehydrogenase). It is interresting that both protozoan-SCP and liver-SCP are interchangeable in cholesterol biosynthesis by liver enzymes and the oxidation of cholesterol to the triene by protozoan enzymes. The effect of numerous hypocholesteraemic compounds on the cyclization of squalene to the pentacyclic triterpenoid tetrahymanol has also been studied in Tetrahymena. ... 

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