The function of vitamin B6 in fat metabolism

Conclusion It is evident that vitamin B₆ serves as a physiological antioxidant. The mechanism cannot be dependent solely on the chemical structure of the vitamin. Despite the favorable arrangement of the substituents, pyridoxine and its derivatives show no, or only slight, antioxidative activityin vitro. The inactivation apparently results from the nature of the pyridine ring. Vitamin B₆ is one of the B vitamins which are required for the normal metabolism of the fats and essential fatty acids. However it still remains to be investigated whether the vitamin is directly associated with fat metabolism or whether the vitamin itself is responsible for the maximum function or the synthesis of enzymes involved. Presented at the 32nd Fall Meeting, American Oil Chemists' Society, October 20–22, 1958, Chicago, Ill.     

Cholesterol metabolism in relation to aging and dietary fat in rats and humans

A review of research in the authors' laboratories regarding effects of dietary fat polyunsaturation upon longevity in rats and some aspects of the regulation of cholesterol metabolism with regard to age of rats and humans is presented. The longevity of the rat was found to be enhanced by consumption of dietary fat providing a polyunsaturated to saturated fatty acid (P/S) ratio of 0.3 to 1, corresponding to about 5–12% of energy (en%) as linoleate, compared with less or more polyunsaturated fat, mechanisms of the effects of the fats upon cholesterol metabolism were studied. With advancing age, there seems to be a decline in the rate of catabolism of cholesterol, resulting in longer retention in the body of the rat. In the human, there seems to be a decline in regulation of uptake of cholesterol by leukocytes and, therefore, perhaps other tissues, resulting in increased synthesis of cholesterol by the peripheral tissues. Moderate rather than high dietary consumption of polyunsaturated fat seems to be favorable to metabolic processes contributing to longevity. Presented at the AOCS meeting in Chicago, May 1983.     

Intestinal metabolism of plasma free fatty acids in streptozotocin diabetic rats

Moderate insulin deficiency was reported to be accompanied by an increased production of intestinal very low density lipoprotein (VLDL) triglyceride in the rat. Because plasma free fatty acids (FFA) are incorporated into triglyceride by intestinal mucosa of rats and humans and plasma FFA are increased in insulin-deficient diabetes mellitus, we investigated several aspects of the intestinal metabolism of plasma FFA in diabetic rats. All experiments were performed on the third day following the i.v. injection of streptozotocin (45 mg/kg body weight) or buffer alone. A (¹⁴C)palmitic acid-rat serum complex was rapidly injected intravenously and its initial uptake by small bowel mucosa, the intracellular incorporation into lipids and water soluble metabolites and the specific radioactivity of triglycerides of mucosal homogenates was determined. No significant differences could be found between diabetic and control rats at 2 and 5 min after¹⁴C-palmitate i.v., suggesting that neither the influx of plasma free fatty acids into intestinal mucosal cells nor their initial intracellular metabolic pathways are significantly altered in moderately diabetic rats. A pronounced decrease in intestinal mucosal triglyceride at 10 min after¹⁴C-palmitate i.v. might be interpreted as indirect evidence for an enhanced triglyceride efflux from intestinal mucosa into mesenteric lymph in diabetic rats.     

Lactose-induced diarrhea increases oxidative stress and it is more severe in rats deficient in vitamin E

Diarrhea is the disease with high incidence in the world and causes infant mortality and malnutrition in the developing world. This justifies the study of nutrition and diarrhea. Due to ethical and financial considerations it is difficult to study nutrition and diarrhea in children thus animal models have become a convenient alternative. In previous studies it was shown that lactose induced diarrhea in rats was associated with a reduction in tissue levels of vitamin E and also with evidence of an inflammatory response of the intestine. Accordingly, in this study, in order to determine the effect of this type of diarrhea on the level of oxidative stress, diarrhea was induced in vitamin E sufficient and deficient rats. The results showed that after 23 days the tissue concentration of vitamin E decreased in all the rats with diarrhea but this reduction was substantially greater in the vitamin E deficient group. Moreover, diarrhea was 60% more severe in the vitamin E deficient rats than in the vitamin E sufficient group that also had diarrhea. Both diarrhea and vitamin E deficiency altered malonaldehyde and superoxide dismutase levels in various tissues. However, the most outstanding changes associated with diarrhea were a 100% increment in plasma malonaldehyde and erythrocyte superoxide dismutase activities which were 8 to 11 times higher than those seen in the rats without diarrhea. These non-invasive changes correlated well with the severity of diarrhea. The study shows that vitamin E deficiency results in diarrheas which are more severe and that lactose induced diarrhea is associated with higher levels of oxidative stress.     

Solubility and heat stability of fat-soluble derivatives of vitamin B6

Summary The heat stability of several fatty acid esters of pyridoxine and their solubility in fats was tested. Short chain fatty acid esters of pyridoxine, such as pyridoxine triacetate, and long chain saturated fatty acid esters of the vitamin, such as pyridoxine tripalmitate were almost insoluble or had a rather limited solubility in fats. An improvement in solubility was observed when pyridoxine was partially esterified with palmitic acid, fully esterified with a long chain unsaturated fatty acid, such as linoleic acid, or when it was esterified with a fatty acid of intermediate chain length (C₆, C₈ or C₁₀). Free pyridoxine and the acetate were destroyed by heat when mixed in a fat and heated at 205–210°C. A profound improvement in heat stability in pyridoxine was noted when one palmitoyl group was introduced, and the ester became completely stable when it was fully esterified with a saturated fatty acid of C₁₀ or longer chain length. Portion of a thesis presented by T. Sakuragi as partial fulfillment of the requirement for the degree of Doctor of Philosophy in Food Technology. This work was supported by research grant No. A-257 from the National Institute of Health, U. S. Public Health Service, Department of Health, Education and Welfare. Presented at the 29th annual meeting of the American Oil Chemists’ Society, Oct. 10–12, 1955, Philadelphia, Pa.     

HPLC法测定复方利血平片中氢氯噻嗪、硫酸双肼屈嗪、维生素B_1和维生素B_6的含量

采用HPLC法测定复方利血平片中氢氯噻嗪、硫酸双肼屈嗪、维生素B1和维生素B6的含量。Kromasil C-18色谱柱（250 mm×4.6 mm,5μm）,检测波长210 nm,以0.2%己烷磺酸钠（用冰醋酸调节pH=3.5）-甲醇-乙腈（75∶20∶5）为流动相,流速1.0 mL/min,进样量20μL,柱温30℃。结果表明,氢氯噻嗪的线性范围为49.6～496.0μg/mL（R2=0.999 4）,精密度RSD为0.12%（n=6）,重复性RSD为0.45%（n=6）,平均回收率为99.74%（RSD=0.78%,n=9）;硫酸双肼屈嗪的线性范围为16.8～336.0μg/mL（R2=0.999 3）,精密度RSD为0.06%（n=6）,重复性RSD为0.21%（n=6）,平均回收率为99.83%（RSD=0.08%,n=9）;维生素B1的线性范围为4.0～80.0μg/mL（R2=0.998 7）,精密度RSD为0.56%（n=6）,重复性RSD为0.96%（n=6）,平均回收率为99.02%（RSD=1.13%,n=9）;维生素B6的线性范围为4.0～80.0μg/mL（R2=0.999 1）,精密度RSD为0.23%（n=6）,重复性RSD为0.78%（n=6）,平均回收率为99.56%（RSD=0.48%,n=9）。此法分离度好,峰形对称,分析周期短,重复性好,简单易行,可同时测定复方利血平片中氢氯噻嗪、硫酸双肼屈嗪、维生素B1和维生素B6的含量。     

Interactions among indicators of B1, B2, B6 and vitamin C status in university students

In 209 young university students (109 males and 80 females) with body mass index within the normal range, the activation coefficient of the erythrocyte transketolase (ETKAC) glutathione reductase (EGRAC) and aspartate amino transferase (EASTAC) as well as the circulating levels of vitamin C were determined. Using the usual cutoff points for ETKAC and serum vitamin C and higher than usual cutoff points for EASTAC and EGRAC 99, 95, 92, and 87% of the study subjects exhibited activation coefficients which were compatible with an acceptable status for vitamin B2, B6, C and B1 respectively. A correlation analysis showed a high correlation (r = 0.81) between erythrocyte indicators of B1 and B2 status a lower correlation between indicators of the status of these vitamins and B6 and no correlation between the indicators of B1, B2, and B6 status and serum vitamin C. This study indicated that in this largely nutritionally adequate population, the activation coefficient of the erythrocyte enzymes used here as markers of the nutritional status of B1, B2, and B6 were related between themselves and varied in the same direction. These changes, however, were not associated with circulating levels of vitamin C.     

Antioxidative activity of derivatives of vitamin B6 and structurally related compounds

Summary Fat-soluble derivatives of vitamin B₆ including ethylN-pyridoxyl-p-aminobenzoate, pyridoxal isonicotinoylhydrazone, and pyridoxine 5-monopalmitate showed little or no antioxidative activity for lard as well as for vitamin A at 37°C. The structurally related compounds, ethylN-vanillyl-p-aminobenzoate, vanillin isonicotinoylhydrazone, and the nicotinoylhydrazone were found to be antioxidants although free vanillin was inactive. The removal of the electron-withdrawing nature at the formyl group in a vanillin molecule might be functional in the development of antioxygenic properties. Evidence was obtained to show that an isonicotinoylhydrazonomethyl group not only activated a phenolic compound as an antioxidant but also removed pro-oxidative metallic ions from lard through chelation. For example, 3,5-di-tert-butyl-4-hydroxybenzaldehyde isonicotinoylhydrazone (BHB-INH), a structural analogue of butylated hydroxytoluene (BHT), stabilized lard more efficiently than BHT on a molar basis in the presence as well as in the absence of Cu⁺⁺. This work was supported by Research Grant No. A-257 from the National Institutes of Health, U. S. Public Health Service, Department of Health, Education, and Welfare. The term “pyridoxyl” denotes the 2-methyl-3-hydroxy-5-hydroxymethyl-4-pyridylmethyl radical. The term “pyridoxylidene” denotes the 2-methyl-3-hydroxy-5-hydroxymethyl-4-pyridylmethylene radical.     

Cholesterol metabolism in frog (Rana esculenta) liver: Seasonal and sex-related variations

Many aspects of lipid metabolism have been studied in amphibians, but seasonal lipid modulation in male and female frogs has not been investigated. We describe here the yearlong patterns of hepatic lipid content and enzyme activities related to cholesterol homeostasis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and acyl coenzyme A:cholesterol acyltransferase (ACAT) activity in liver of the male and female frog,Rana esculenta. Lipid storage follows distinct seasonal patterns, with an increase in June that is more pronounced in the female than in the male frog. Cholesterol content and cholesterol storage as cholesteryl ester in male liver are consistent with the activity of HMG-CoA reductase and of ACAT enzymes. HMG-CoA reductase activity of the female frog shows an extra peak in fall unrelated to cholesterol storage and probably related to the production of essential compound for oogenesis.     

Mechanism of suckling-rat hypercholesteremia. II. Cholesterol biosynthesis and cholic acid turnover studies

Cholesterol biosynthesis from acetate-2-¹⁴C by the livers of suckling rats, which is known to be relatively slow, was increased 2–3-fold within 24 hours after severing the bile duct. Cholesterol synthesis by sham-operated litter mates showed no change under similar treatment. Mevalonate biosynthesis from acetate-2-¹⁴C in vitro by recombined liver microsomal supernatant (105,000×g) fractions from suckling rats also was only 10% of that of comparable recombined fractions from normal controls (young adult rats which were consuming colony diet). Activity was not improved by combining either the microsomal or supernatant fraction from suckling rat livers with the complementary fraction from normal adult livers. On the other hand, activity was restored to 100% when microsomes from livers of duct-served suckling rats were combined with the supernatant fraction from normal controls. Likewise, recombined liver fractions prepared from adult rats fed synthetic diets exhibited low activity for mevalonate biosynthesis. Activity was restored by bile duct cannulation, but inhibited when cholic acid was infused into the cannulated animal. Therefore, surgical procedures which interrupt the enterohepatic recirculation of bile components lead to a restoration of cholesterol biosynthesis and, at least in the adult animal where cannulation studies are practicable, this effect can be reversed readily by bile acid infusion. A slow rate of fecal excretion of¹⁴C-cholic acid was observed in suckling rats and rats fed synthetic diets, apparently reflecting an efficient enterohepatic recirculation of bile salts. The data suggest that under these dietary conditions bile salt retention either directly or indirectly influences hepatic synthesis of cholesterol. Presented in part before Federation of American Societies for Experimental Biology, Fed. Proc.24, 1078, 1965 (abstract). and in part at the AOCS Meeting, Los Angeles, April 1966. Journal Paper No.2835, Purdue University Agricultural Experiment Station.     

NPC1L1 and SR-BI are Involved in Intestinal Cholesterol Absorption from Small-Size Lipid Donors

In the human intestinal content after a meal, cholesterol is dispersed in a complex mixture of emulsified droplets, vesicles, mixed micelles and precipitated material. The aim of this study was to determine the contribution of the main intestinal cholesterol transporters (NPC1L1, SR-BI) to the absorption processes, using different cholesterol-solubilizing donors. Cholesterol donors prepared with different taurocholate concentrations were added to an apical medium of differentiated TC7/Caco-2 cells. As the taurocholate concentrations increased, cholesterol donor size decreased (from 712 to 7 nm in diameter), which enhanced cholesterol absorption in a dose-dependent manner (38-fold). Two transport processes were observed: (1) absorption from large donors exhibited low-capacity transport with no noticeable transporter contribution; (2) efficient cholesterol absorption occurs from small lipid donors (相似文献   

Cholesterol metabolism in the rat lactating mammary gland: The role of cholesteryl ester hydrolase

An acid cholesteryl ester hydrolase activity associated with a fraction containing mitochondria and lysosomes from rat lactating mammary glands was found to have a pH optimum of 5.0. Its sedimentation pattern was closely related to that of the lysosomal enzyme markers acid phosphatase and β-glucuronidase, suggesting that the activity is associated with the lysosomes. The enzyme was strongly inhibited by Cu²⁺, but was inhibited little by other divalent metal ions. Acid cholesteryl ester hydrolase activity was almost completely abolished byp-hydroxymercuribenzoate, but this effect was reversed in the presence of an equimolar concentration of reduced glutathione (GSH), indicating that the enzyme requires free sulfhydryl groups for activity. These properties are similar to those of acid, lysosomal cholesteryl ester hydrolases found in other tissues. Acid cholesteryl ester hydrolase activity was 8–14 fold higher in mammary tissue from lactating as compared to virgin rats. Neutral cholesteryl ester hydrolase activities associated with the microsomal and cytosolic subcellular fractions were also increased in lactating glands, but to a lesser extent. In addition, a 2-fold increase in the activities of both the acid and microsomal neutral enzymes was seen during the first few days of lactation, while the cytosolic neutral activity remained constant. These results suggest that mammary gland cholesteryl ester hydrolases have a role in the regulation of cholesterol metabolism in mammary cells, and in the provision of cholesterol for secretion into milk.     

Cholesterol oxides II. Measurement of the 5,6-epoxides during cholesterol oxidation in aqueous dispersions

Cholesterol in aqueous dispersion with sodium stearate or Triton surfactants was aerated at various pH values at 50 and 80 C. Analysis of the reaction mixtures by TLC during the oxidation produced qualitatively similar patterns regardless of pH or temperature. Major oxidation products observed were 7-ketocholesterol, the isomeric 7-hydroperoxy- and 7-hydroxycholesterols, the isomeric 5,6-epoxycholestanols and 3β,5α,6β-trihydroxycholestanol. The concentrations of 3β,5α,6β-trihydroxycholestanol and an unknown compound increased greatly at the lower pH values. Recovery of the 5,6-epoxide isomers by preparative TLC followed by capillary GC allowed theα- andβ-epoxide isomers to be quantitated. Oxidations at pH 8 and 12 produced increasing amounts of the epoxides with time, without significant changes in theα/β-epoxide ratio. However, oxidations at the acidic pH values of 5.5 and 3 showed large changes in theα/β-epoxide ratio during the oxidation. Measurement of the hydrolysis rates of the 5,6-epoxides at pH 5.5 showed that theβ-epoxide isomer is more labile than theα-isomer by a factor of 2.5. The rate constant for the hydrolysis of theα-epoxide isomer was 5.3 × 10⁻⁷ sec⁻¹ and that of theβ-isomer 13 × 10⁻⁷ sec⁻¹.     

SHS in preliminary structured compacts: II. Ti-2B and Ti-Al blends

Stepwise densification of Ti-2B and Ti-Al blends was used to prepare green compacts with an ordered structure. The latter ones were then used to explore combustion synthesis in these mixtures with special emphasis on the possibility of inheriting a structure of green compact by a combustion product. It has been demonstrated that, at some certain conditions, an ordered structure of green compact can be inherited by a combustion-synthesized product.     

Fatty acid metabolism inDrosophila melanogaster: II. Metabolic origin of monoenes

Evidence is presented thatDrosophila larvae produce monounsaturated fatty acids by two independent pathways. One of these pathways, involving the direct desaturation of long chain precursors, is sensitive to inhibition by linoleate. The other pathway is resistant to linoleate inhibition and probably has tetradecnoate-Δ⁵ cis and tetradecnoate-Δ⁷ cis as intermediates in the synthesis of palmitoleate and oleate, respectively. The use of radioactive precursors of varying chain length and labeled at different positions in the carbon chains provided evidence for the isolation and structure of intermediates involved in the linoleate resistant pathway.