Δ-THC and 11-OH-Δ-THC: Behavioral effects and relationship to plasma and brain levels

The time course of effects following i.p. injections of 0.3–10.0 mg/kg Δ⁹-tetrahydrocannabinol (δ⁹-THC) and 0.1–3.0 mg/kg 11-OH-Δ⁹-THC were determined in rats during 6 hour sessions under a fixed-interval 90-second schedule of food reinforcement. In addition, the acute and chronic effects of these two drugs were tested in different rats trained on a differential reinforcement of low rate 15-second schedule. The onset of activity of 11-OH-Δ⁹-THC was faster, and usually abruptly suppressed all responding, while Δ⁹-THC's onset was slower and often resulted in a decreased and steady pattern of responding. 11-OH-Δ⁹-THC was about 3 times more potent, had a shorter duration of effect and when responding resumed, it returned to control rates within a shorter time than for Δ⁹-THC. Tolerance and cross-tolerance developed at the same rate to equipotent doses of the two drugs. The time course for plasma and brain levels of radioactivity were studied in other rats after i.p. administration of H³-Δ⁹-THC and H³-11-OH-Δ⁹-THC. 11-OH-Δ⁹-THC was absorbed more quickly than Δ⁹-THC and reached peak plasma and brain levels earlier. In addition, higher plasma and brain levels, and larger brain to plasma ratio of radioactivity were attained after 11-OH-Δ⁹-THC. Therefore, differences in behavioral effects produced by Δ⁹-THC and it's 11-hydroxy metabolite were accompanied by differences in absorption and disposition.     

Δ-β-Sitosten-3-one from β-sitosterol by leaf homogenates

β-Sitosterol-4-¹⁴C is metabolized to Δ⁴-β-sitosten-3-one by Cheiranthus cheiri leaf homogenates. Greater than 60% conversion occurs within 2 hr. Under identical conditions, leaf homogenates of Strophanthus kombé fail to metabolize β-sitosterol, while Digitalis purpurea leaf homogenates yield only very small amounts of the metabolite.     

Identification of a cDNA encoding a novel C18-Δ polyunsaturated fatty acid-specific elongating activity from the docosahexaenoic acid (DHA)-producing microalga, Isochrysis galbana

Isochrysis galbana, a marine prymnesiophyte microalga, is rich in long chain polyunsaturated fatty acids such as docosahexaenoic acid (C22:6n-3, Δ^{4,7,10,13,16,19}). We used a polymerase chain reaction-based strategy to isolate a cDNA, designated IgASE1, encoding a polyunsaturated fatty acid-elongating activity from I. galbana. The coding region of 263 amino acids predicts a protein of 30 kDa that shares only limited homology to animal and fungal proteins with elongating activity. Functional analysis of IgASE1, by expression in Saccharomyces cerevisiae, was used to determine its activity and substrate specificity. Transformed yeast cells specifically elongated the C18-Δ⁹ polyunsaturated fatty acids, linoleic acid (C18:2n-6, Δ^9,12) and -linolenic acid (C18:3n-3, Δ^9,12,15), to eicosadienoic acid (C20:2n-6, Δ^11,14) and eicosatrienoic acid (C20:3n-3, Δ^11,14,17), respectively. To our knowledge this is the first time such an elongating activity has been functionally characterised. The results also suggest that a major route for eicosapentaenoic acid (C20:5n-3, Δ^5,8,11,14,17) and docosahexaenoic acid syntheses in I. galbana may involve a Δ⁸ desaturation pathway.     

Biological aromatization of delta4,6- and delta1,4,6-androgens and their 6-alkyl analogs, potent inhibitors of aromatase

Enzymic aromatization of Δ⁶- and Δ^1,6-derivatives of the natural substrate androstenedione with human placental aromatase was first studied using gas-chromatography-mass spectrometry. The two steroids were aromatized with apparent K_m and V_max values of 62 nM and 32 pmol/min/mg protein for the Δ⁶-steroid and 167 nM and 10 pmol/min/mg protein for the Δ^1,6-steroid, respectively. We next explored the aromatization of a series of 6-alkyl (methyl, ethyl, n-propyl, and n-pentyl)-substituted Δ⁶-androstenediones and their Δ^1,6-analogs, potent competitive inhibitors of aromatase, to gain insight into the relationships between the inhibitory activity of the 6-alkyl-C₁₉ steroids and their ability to serve as a substrate of aromatase. In a series of the Δ^1,6-androstenediones, all the 6-alkyl steroids were more efficient substrates than the parent Δ^1,6-steroid in which the aromatization rates of the alkyl steroids were about 2-fold that of the parent steroid, in contrast, all of the 6-alkyl-substituted Δ⁶-androstenediones were converted into the corresponding 6-alkyl-Δ⁶-estrogens with the rates of less than about a half that of the parent steroid. These results indicate that the 6-alkyl function decreases the aromatization rate of the Δ⁶-steroid but enhances that of the Δ^1,6-steroid. The relative apparent K_m values for the C₁₉ steroids obtained in this study are different from the relative K_i values obtained previously, indicating that a good inhibitor is not essentially a good substrate in the 6-alkyl-substituted Δ⁶- and Δ^1,6-androstenedione series.     

Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and -independent processes

The ability of 2-n-propyl-4-pentenoic acid (Δ⁴-VPA) and 2-n-propyl-2(E)-pentenoic acid ([E]-Δ²-VPA), two unsaturated metabolites of valproic acid (VPA), to form reactive intermediates, deplete hepatic glutathione (GSH) and cause accumulation of liver triglycerides was investigated in the rat. With the aid of ionspray liquid chromatography-tandem mass spectrometry (LC-MS/MS), three GSH adducts were detected in the bile of Δ⁴-VPA-treated animals and were identified as 4-hydroxy-5-glutathion-S-yl-VPA-γ-lactone, 5-glutathion-S-yl-(E)-Δ³-VPA and 3-oxo-5-glutathion-S-yl-VPA. A fourth conjugate was identified tentatively as 4-glutathion-S-yl-5-hydroxy-VPA. Quantitative analysis of the corresponding N-acetylcysteine (NAC) conjugates in urine indicated that metabolism of Δ⁴-VPA via the GSH-dependent pathways accounted for approximately 20% of an acute dose (100 mg kg⁻¹ i.p.). In contrast, when rats were given an equivalent dose of (E)-Δ²-VPA, only one GSH adduct (5-glutathion-S-yl-(E)-Δ³-VPA) was detected at low concentrations in bile. In vitro experiments with rat liver mitochondria demonstrated that Δ⁴-VPA undergoes coenzyme A- and ATP-dependent metabolic activation in this organelle via the β-oxidation pathway to intermediates which bind covalently to proteins. When liver homogenates and hepatic mitochondria from rats injected with Δ⁴-VPA, (E)-Δ²-VPA or VPA were analyzed for GSH content, it was found that only Δ⁴-VPA depleted GSH pools significantly. Treatment of rats with Δ⁴-VPA and (to a lesser extent) VPA led to an accumulation of liver triglycerides, whereas (E)-Δ²-VPA had no measurable effect. It is concluded that Δ⁴-VPA undergoes metabolic activation by both microsomal cytochrome P-450-dependent and mitochondrial coenzyme A-dependent processes, and that the resulting electrophilic intermediates, which are trapped in part by GSH, may mediate the hepatotoxic effects of this compound. In contrast, (E)-Δ²-VPA is not transformed to any appreciable extent to reactive metabolites, which thus accounts for the apparent lack of hepatotoxicity of this positional isomer in the rat.     

Expression and evolution of delta9 and delta11 desaturase genes in the moth Spodoptera littoralis

Desaturation of fatty acids is a key reaction in the biosynthesis of moth sex pheromones. The main component of Spodoptera littoralis sex pheromone blend is produced by the action of Δ¹¹ and Δ⁹ desaturases. In this article, we report on the cloning of four desaturase-like genes in this species: one from the fat body (Sls-FL1) and three (Sls-FL2, Sls-FL3 and Sls-FL4) from the pheromone gland. By means of a computational/phylogenetic method, as well as functional assays, the desaturase gene products have been characterized. The fat body gene expressed a Δ⁹ desaturase that produced (Z)-9-hexadecenoic and (Z)-9-octadecenoic acids in a (1:4.5) ratio, whereas the pheromone gland Sls-FL2 expressed a Δ⁹ desaturase that produced (Z)-9-hexadecenoic and (Z)-9-octadecenoic acids in a (1.5:1) ratio. Although both Δ⁹ desaturases produced (Z)-9-tetradecenoic acid from myristic acid, transformed yeast grown in the presence of a mixture of myristic and (E)-11-tetradecenoic acids produced (Z,E)-9,11-tetradecadienoic acid, but not (Z)-9-tetradecenoic acid. The Sls-FL3 gene expressed a protein that produced a mixture of (E)-11-tetradecenoic, (Z)-11-tetradecenoic, (Z)-11-hexadecenoic and (Z)-11-octadecenoic acids in a 5:4:60:31 ratio. Despite having all the characteristics of a desaturase gene, no function could be found for Sls-FL4.     

Determination of free energies in reaction centers of Rb. sphaeroides

Magnetic field-dependent recombination measurements together with magnetic field-dependent triplet lifetimes (Chidsey, E.D., Takiff, L., Goldstein, R.A. and Boxer, S.G. (1985) Proc. Natl. Acad. Sci USA 82, 6850–6854) yield a free energy change ΔG(P⁺H⁻ − ³P*) = 0.165 eV ±0.008 at 290 K. This does not depend on whether nuclear spin relaxation in the state ³P* is assumed to be fast or slow compared to the lifetime of this state. This value, being (almost) temperature independent, indicates ΔG(P⁺H⁻ − ³P*) ΔH(P⁺H⁻ − ³P*) and is consistent with ΔG(¹P* − P⁺H⁻) and ΔH(¹P* − ³P*) from previous delayed fluorescence and phosphorescence data, implying ΔG ΔH for all combinations of these states.     

Occurrence of singlet oxygen oxygenation of oleic acid and linoleic acid in the skin of live mice

To assess the contribution of singlet molecular oxygen [O₂ (¹Δ_g)] to lipid peroxidation in vivo, this study combined gas chromatography-mass spectrometry with thin layer chromatography to analyse peroxidized lipids in the skin of hairless mice. Hydroxyoctadecenoate isomers and unconjugated hydroxyoctadecadienoate isomers derived from peroxidized oleic acid and linoleic acid, respectively, which are specific to O₂ (¹Δ_g)-dependent oxygenation, were detected in the skin of live mice under ordinary feeding conditions. Short-term ultraviolet A (UVA)-irradiation of the skin in vivo elevated levels of the unconjugated hydroxyoctadecadienoate isomers significantly, whereas the irradiation of skin homogenate in vitro increased levels of all isomers derived from both O₂ (¹Δ_g) and free radical-dependent oxygenation to a much greater extent. This is the first report to demonstrate the occurrence of O₂ (¹Δ_g)-specific oxygenation of unsaturated fatty acids in living animals.     

High-efficiency expression of rat protein kinase C-gamma in baculovirus-infected insect cells

Effects of cyclopentenone prostaglandins, Δ¹²-prostaglandin (PG) J₂ and PGA₂ on the expression of N-myc in relation to the effects on cell cycle progression were investigated using human neuroblastoma cell line GOTO. Both PGs suppressed M-myc expression within several hours prior to inducing G₁ arrest. The N-myc suppression with Δ¹²-PGJ₂ was continued but with PGA₂ it was gradually released, followed by the release of G₁ arrest. These results suggest that Δ¹²-PGJ₂ and PGA₂ inhibit cell cycle progression in strong association with N-myc suppression and Δ¹²-PGJ₂ is more potent and has a longer effect than PGA₂.     

Metabolism of steroid hormones by Taenia solium and Taenia crassiceps cysticerci

Previous in vitro experiments showed that both, Taenia crassiceps and Taenia solium cysticerci have the ability to metabolize exogenous androstenedione to testosterone. Here we evaluate on the capacity of both cysticerci to synthesize several sex steroid hormones, using different hormonal precursors. Experiments using thin layer chromatography (TLC) showed that both cysticerci were able to produce ³H-hydroxyprogesterone, ³H-androstenedione and ³H-testosterone when ³H-progesterone was used as the precursor. They also synthesized ³H-androstenediol and ³H-testosterone when ³H-dehydroepiandrosterone was the precursor. In addition, both cysticerci interconverted ³H-estradiol and ³H-estrone. These results, strongly suggest the presence and activity of the Δ4 and Δ5 steroid pathway enzymes, 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase-like enzyme (3β-HSD), that converts androstenediol into testosterone; and the 17β-hydroxysteroid dehydrogenase that interconverts estradiol and estrone, in both types of cysticerci.     

Tibolone and metabolites induce prolactin production in human endometrial stromal cells in vitro: evidence for cell-specific metabolism

In this study, we assessed the effects of tibolone and its metabolites on the production of a progesterone sensitive parameter, prolactin, in human endometrium stroma cells in vitro. In addition, the metabolism of the compounds by isolated stromal and epithelial cells was evaluated.

The reference compounds, progesterone, Org 2058, and DHT all induced prolactin production. Oestradiol also slightly induced prolactin production and enhanced the response to Org 2058. Tibolone and Δ⁴-tibolone were similar with regard to potency to induce prolactin levels in the culture supernatant. Their potency was lower than that of Org 2058, similar to that of progesterone and higher than that of DHT. The efficacies of tibolone, Δ⁴-tibolone and Org 2058 were similar (200-fold induction). The estrogenic tibolone metabolites 3- and 3β-OH tibolone also significantly stimulated prolactin production. Their potency, however, was low since significance was reached only at the highest concentrations tested.

The PR antagonist Org 31710 inhibited both tibolone- and Δ⁴-tibolone-induced prolactin production. The responses of tibolone and Δ⁴-tibolone were not affected by co-incubation with the androgen receptor antagonist OH-flutamide. The effect of tibolone, but not Δ⁴-tibolone, was antagonized approximately 50% in combination with the highest dose (1 μM) estrogen receptor antagonist, ICI 164384. The induction of prolactin by 3- and 3β-OH tibolone was antagonized most potently by Org 31710, but also by ICI 164384 and OH-flutamide.

Tibolone is metabolized differently in epithelial and stromal cells of the human endometrium. The epithelial cells mostly produce the progestagenic/androgenic Δ⁴-tibolone. The stromal cells produce predominantly the 3β-OH tibolone, and some Δ⁴-tibolone, but the net effect observed with regard to prolactin production is progestagenic. When the metabolites 3-OH, 3β-OH, and Δ⁴-tibolone were added to the cultures no conversions were observed. The HPLC analyses showed no evidence for the production of sulfated metabolites.

In conclusion, the net effects on endometrial stromal cells are predominantly progestagenic. Tibolone is converted by epithelial cells into Δ⁴-tibolone which displays progestagenic and androgenic activities, whereas in stromal cells also the estrogenic metabolites 3- and 3β-OH tibolone are formed.     

Synthesis and pharmacology of the isomeric methylheptyl-Δ-tetrahydrocannabinols

The synthesis of the 3-heptyl, and the eleven isomeric 3-methylheptyl-Δ⁸-tetrahydrocannabinols (3–7, R and S methyl epimers, and 8) has been carried out. The synthetic approach entailed the synthesis of substituted resorcinols, which were subjected to acid catalyzed condensation with trans-para-menthadienol to provide the Δ⁸-THC analogue. The 1′-, 2′- and 3′-methylheptyl analogues (3–5) are considerably more potent than Δ⁸-THC. The 4′-, 5′- and 6′-methylheptyl isomers (6–8) are approximately equal in potency to Δ⁸-THC.     

The interaction of Lewis acidic boron derivatives with Re(CO)5−nH(PMe3)n complexes

Lewis acid adducts of the hydrides cis- and trans-Re(CO)(PMe₃)₄H (1) and (2), mer-Re(CO)₂(PMe₃)₃H (3), fac-Re(CO)₂(PMe₃)₃H (4) and trans-Re(CO)₃(PMe₃)₂H (5) were studied with BH₃ and 9-borabicyclo[3,3,1] norbonane (BBNH). Using BH₃·THF and (BBNH)₂ 1 and 2 afforded Re(CO)(PMe₃)₃(η²-BH₄) (6) and Re(CO)(PMe₃)₃(η²-BBNH₂) (7) as stable and isolable products. VT IR studies established for the reaction to 7 that BBNH first attaches in a pre-equilibrium to the O_CO atom of 1 or 2. At higher temperatures ReH adduct formation occurs with instantaneous transformation to 7 and elimination of PMe₃·BBNH. In a similar way, the hydrides 3 and 4 were converted with BH₃·THF and (BBNH)₂ to yield the stable complexes Re(CO)₂(PMe₃)₂(η²-BH₄) (8) and Re(CO)₂(PMe₃)₂(η²-BBNH₂) (9). The intermediacy of the η¹-BH₄ adducts mer-/fac-Re(CO)₂(PMe₃)₃(η¹-BH₄) was confirmed by VT ¹H, ³¹P NMR and VT IR experiments. The conversion of 5 with BH₃·THF led to equilibria with adducts at the O_CO terminus in trans position to H and with H_Re as revealed by VT IR studies. Temperature dependent ³¹P equilibrium studies allowed to calculate ΔH=−4.9 kcal mol⁻¹ and ΔS=+0.034 e.u. for this reaction. These adducts could not be isolated. Compound 5 does not react with (BBNH)₂ even at elevated temperatures. DFT calculations were carried out to support the structures of the BH₃ adducts of 5. In addition a vibrational analysis helped to unravel the IR band assignments of the involved compounds. DFT calculations on 8 confirmed its C_2v structure. X-ray diffraction studies were carried out on single crystals of 6 and 7.     

Rate of electron transfer between plastocyanin, cytochrome ƒ, related proteins and artificial redox reagents in solution

The rate of electron transfer between reduced cytochrome ƒ and plastocyanin (both purified from parsley) has been measured as k = 3.6 · 10⁷ M⁻¹ · s⁻¹, at 298 °K and pH 7.0, with activation parameters ΔH^‡ = 44 kJ · mole⁻¹ and ΔS^‡ = +46 J · mole⁻¹ · °K⁻¹. Replacement of cytochrome ƒ with red algal cytochrome c-553, Pseudomonas cytochrome c-551 and mammalian cytochrome c gave rates at least 30 times slower: k = 5 · 10⁵, 7.5 · 10⁵ and 1.0 · 10⁶ M⁻¹ · s⁻¹, respectively.

Similar measurements made with azurin instead of plastocyanin gave k = 6 · 10⁶ and approx. 2 · 10⁷ M⁻¹ · s⁻¹ for reaction of reduced azurin with cytochrome ƒ and algal cytochrome respectively.

Rate constants of 115 and 80 M⁻¹ · s⁻¹ were found for reduction of plastocyanin by ascorbate and hydroquinone at 298 °K and pH 7.0. The rate constants for the oxidation of plastocyanin, cytochrome ƒ, Pseudomonas cytochrome c-551 and red algal cytochrome c-553 by ferricyanide were found to be between 3 · 10⁴ and 8 · 10⁴ M⁻¹ · s⁻¹.

The results are discussed in relation to photosynthetic electron transport.     

Ricochet inter-ring haptotropic rearrangement of σ-methyl-(η-indenyl) chromium tricarbonyls. Experimental kinetic and theoretical DFT study

σ-Methyl-(η⁵-indenyl) chromium tricarbonyl (III) rearranges quantitatively into η⁶-1-endo-methylindene) chromium tricarbonyl (IV) in C₆D₆ solution at 30–60°C. Methyl group attachment to the positions 2 or 3 of indenyl ligand in (III) has no influence on the activation parameters of this ricochet inter-ring haptotropic rearrangement (ΔG^#=23.6 kcal mol⁻¹; ΔH^#=18.9±0.2 kcal mol⁻¹; ΔS^#=−18.6±0.2 cal K⁻¹ mol⁻¹). (IV) undergoes further irreversible isomerization at 60–120° into (ν⁶-3-methylindene) chromium tricarbonyl (V) with a higher activation barrier (ΔG^#=28.5±0.1 kcal mol⁻¹) via two consecutive [1,5]-sigmatropic hydrogen shifts. The mechanisms of both rearrangements have been studied in detail using density functional theory (DFT) calculations with extended basis sets. Calculations show that the rearrangement (III) → (IV) proceeds in two steps. Methyl group migration from chromium into position 1 of the indenyl ligand is the rate-determining step leading to the formation of the 16-electron intermediate (VII). The calculated activation barrier (E_a=19.6 kcal mol⁻¹) is in good agreement with the experimental one. Further rearrangement (VII) → (V) proceeds via a trimethylenemethane-type transition state (XVIII) with an activation barrier 11.8 kcal mol⁻¹. The coordination of the chromium tricarbonyl group at the six-membered ring has only minor influence on the kinetic parameters of the hydrogen [1,5]-sigmatropic shift in indene.     

In vitro steroid metabolic studies in human testes II: Metabolism of cholesterol, pregnenolone, progesterone, androstenedione and testosterone by testes of an estrogen-treated man

The effect of long-term in vivo estrogen treatment on in vitro steroidogenesis by the testes of a young man was investigated. In vitro incubation of testicular tissue of this man with ³H-pregnenolone, ³H-progesterone, ³H-androstenedione and ³H-testosterone demonstrated suppression of 17-hydroxylase activity, with little or no effect of the treatment on Δ⁵-3β-hydroxysteroid oxidoreductase, 5a-reductase and aromatase. Increased 20-hydroxysteroid oxidoreductase activity was observed. Determination of intratesticular steroid concentrations led to similar conclusions.     

Late Quaternary paleoproductivity changes off the Congo deduced from stable carbon isotopes of planktonic foraminifera

A detailed record (≈2-kyr intervals) of the difference in stable carbon isotopes (Δδ¹³C) between Globigerina bulloides and Globigerinoides ruber (pink) is used to reconstruct changes in upwelling intensity off the Congo River for the last 190,000 yr. Comparisons of the oxygen and carbon isotope data from this core with records from the Niger Fan and from pelagic cores in the eastern equatorial South Atlantic indicate that the Congo Fan isotope records do not contain a strong freshwater signal as is described off other major rivers. The temporal pattern of the Δδ¹³C signal correlates with the marine organic carbon record from the Congo Fan. Thus the planktonic Δδ¹³C record, reflecting past changes in upwelling intensity and nutrient content, corroborates the signal provided by sedimentary organic carbon, which is presumed to indicate changes in the amount of biological productivity and export flux to the seafloor.

The planktonic Δδ¹³C signal is characterized by a dominant 23-kyr periodicity which provides evidence for a strong response of upwelling fluctuations off the Congo to precessional forcing. Minima in the Δδ¹³C record are aligned with periods of minimum boreal summer insolation over Central Africa reflecting an increase of upwelling and biological productivity off the Congo at periods of enhanced zonal intensity of southeast trades and corresponding weak southeast monsoon over the eastern South Atlantic. A strong response to changes in river discharge probably did not occur, indicating that fertilization by river-derived nutrients has played only a minor role with respect to Late Quaternary changes in the total amount of primary productivity off the Congo.     

Proton nuclear magnetic resonance study of N,N-diethylformamide exchange on (N,N-diethylformamide)2,2′2″-tris(dimethylamino)triethylamine)cobalt(II) and its copper(II) analogue

Proton NMR studies of N,N-diethylformamide (def) exchange on [M(Me₆tren)def]²⁺ where M = Co and Cu yield: k_ex (298.2K) = 26.3 ± 2.2, 980 ± 70 s⁻¹; ΔH^≠ = 58.3 ± 1.7, 36.3 ± 0.9 kJ mol⁻¹; ΔS^≠= −22.2 ± 4.6, −65.9 ± 2.5 J K⁻¹ mol⁻¹; and ΔV^≠ = −1.3 ± 0.2, 5.3 ± 0.3 cm³ mol⁻¹ respectively. These data which are consistent with a and d activation modes operating when M = Co and Cu respectively are compared with data for related systems.     

On the Specificity of Allopurinol and Oxypurinol as Inhibitors of Xanthine Oxidase. A Pulse Radiolysis Determination of Rate Constants for Reaction of Allopurinol and Oxypurinol with Hydroxyl Radicals

Allopurinol has been employed as a “specific” inhihitor of xanthine oxidase in studies of hypoxic/ reoxygenation injury. Pulse radiolysis was used to establish rate constants for the reactions of allopurinol and its major metabolite oxypurinol with hydroxyl radicals: values were (1.45 ± 0.241 × 10⁹ M^-1 s^-1 for allopurinol and (4.95 ± 0.84) × 10⁹ M^-1 s^-1 for oxypurinol. These rate constants show that, in view of the amounts of allopurinol that have been used in animal studies. hydroxyl radical scavenging by this molecule could contribute to its biological actions. especially if animals are pre-treated with allopurinol. so allowing oxypurinol to form. The ability of allopurinol to protect tissues not containing xanthine oxidase against reoxygenation injury may be related to radical scavenging by allopurinol and oxypurinol.     

Variations in the activity of fatty ACYL-CoA desaturases and electron-transport components in Tetrahymena microsomes with temperature and age of culture

1. 1.|Alterations in the fatty acid composition of microsomes were most marked in the exponential phase of both 39.5- or 15°C- grown Tetrahymena pyriformis NT-1.

2. 2.|Activities of palmitoyl-CoA and stearoyl-CoA desaturases were lower in 15°C cells than in 39.5°C cells, while the activity of oleoyl-CoA desaturase was higher in 15°C cells.

3. 3.|Activities of the terminal component of the desaturation system as well as all three desaturases (palmitoyl-CoA, stearoyl-CoA, oleoyl-CoA) were higher in the exponential phase than in the stationary phase for cells grown at both temperatures.

4. 4.|NAD(P)H-cytochrome c reductase activity and cytochrome b₅ content were reduced whereas NADH-ferricyanide reductase activity was increased in the stationary phase at both 39.5 and 15°C.