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101.
随着生物制药的迅速发展,许多酶类药物应运而生,在治疗代谢疾病、心血管疾病、癌症等诸多疾病上发挥着越来越重要的作用。但是酶类药物也存在一些不足,如潜在的免疫原性、较短的体内半衰期,以及较差的组织靶向性,影响了酶类药物的疗效和应用。为克服这些缺点,人们已开发出多种技术,如通过糖基化、聚乙二醇修饰等分子工程技术提升酶蛋白药效,另一方面酶基因疗法也已成功用于多种酶缺陷疾病的治疗。基于酶类药物的迅速发展和广泛的应用前景,本文对酶类药物的现状进行较详细的阐述,并对酶类药物的优势、所存在的问题及未来发展趋势进行分析和评述。 相似文献
102.
Bao Yang Jianwu Li Jiayu Yan Ke Zhang Zhewen Ouyang Yefei Lu Huili Wei Qing Li Xuan Yao Shaoping Lu Yueyun Hong Xuemin Wang Liang Guo 《植物学报(英文版)》2023,65(11):2421-2436
Phosphorus is a major nutrient vital for plant growth and development, with a substantial amount of cellular phosphorus being used for the biosynthesis of membrane phospholipids. Here, we report that NON-SPECIFIC PHOSPHOLIPASE C4 (NPC4) in rapeseed (Brassica napus) releases phosphate from phospholipids to promote growth and seed yield, as plants with altered NPC4 levels showed significant changes in seed production under different phosphate conditions. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated knockout of BnaNPC4 led to elevated accumulation of phospholipids and decreased growth, whereas overexpression (OE) of BnaNPC4 resulted in lower phospholipid contents and increased plant growth and seed production. We demonstrate that BnaNPC4 hydrolyzes phosphosphingolipids and phosphoglycerolipids in vitro, and plants with altered BnaNPC4 function displayed changes in their sphingolipid and glycerolipid contents in roots, with a greater change in glycerolipids than sphingolipids in leaves, particularly under phosphate deficiency conditions. In addition, BnaNPC4-OE plants led to the upregulation of genes involved in lipid metabolism, phosphate release, and phosphate transport and an increase in free inorganic phosphate in leaves. These results indicate that BnaNPC4 hydrolyzes phosphosphingolipids and phosphoglycerolipids in rapeseed to enhance phosphate release from membrane phospholipids and promote growth and seed production. 相似文献
103.
104.
Regulation of oxidative phosphorylation: The flexible respiratory network ofParacoccus denitrificans
105.
We examined the effect of methionine deficiency on iodothyronine 5’-deiodinase activity in selenium-deficient rats or selenium-sufficient
rats fed sodium selenate or selenomethionine. Forty-two weanling male Wistar rats were divided into six groups and pair fed
the respective purifiedl-amino acid-based diets for 4 wk.l-methionine concentrations in the diet were 8.0 g/kg for sufficient rats, and 2.0 g/kg for deficient rats. Selenium concentrations
in the diet were 0.5 mg/kg (as sodium selenate or selenomethionine) for selenium-sufficient rats and less than 0.005 mg/kg
for selenium-deficient rats. Type I 5’-deiodinase activities were significantly lower in liver and higher in kidney of methionine-deficient
rats than in those of methionine-sufficient rats fed either the selenium-sufficient or the selenium-deficient diets. The type
I 5’-deiodinase activity in brain was significantly lower in the methionine-deficient rats than in the methionine-sufficient
rats fed the selenium-deficient diet. Type II 5’-deiodinase activity in brain was significantly higher in the methionine-deficient
rats than in the methionine-sufficient rats fed selenium-sufficient diet as sodium selenate. Both thyroxine and 3,3’,5-triiodothyronine
concentrations in plasma were significantly higher in the methionine-deficient rats than in the methionine-sufficient rats.
It is suggested that the methionine deficiency affects the 5’-deiodinase activity and thyroid hormones level in the rats. 相似文献
106.
The present study was conducted to investigate the effect of zinc deficiency on fatty acid desaturation in rats fed two different
types of dietary fat, a mixture of coconut oil and safflower oil (7∶1, w/w, “coconut oil diet”) or linseed oil (“linseed oil
diet”). In order to ensure an adequate food intake, all rats were force-fed by gastric tube. Zinc deficiency caused statistical
significant reducion of Δ9-desaturase activity in liver microsomes of rats fed coconut oil diet and tendencial reduction (p<0.15) in rats fed linseed oil diet compared with control rats fed diets with the same type of fat. In agreement with this
effect, zinc deficiency in the rats fed both types of dietary fat increased the ratio between total saturated and total monounsaturated
fatty in liver phospholipids and liver microsomes. Zinc deficient rats on the coconut oil diet had unchanged Δ6-desaturase
activity with linoleic acid as substrate and lowered activity with α-linolenic acid as substrate. In contrast, zinc deficient
rats on the linseed oil diet had increased Δ6-desaturase activity with linoleic acid as substrate and unchanged activity with
α-linolenic acid. Because linoleic acid is the main substrate for Δ6-desaturase in the rats fed coconut oil diet, and α-linolenic
acid is the main substrate in the rats fed linseed oil diet, it is concluded that in vivo Δ6-desaturation was not changed
by zinc deficiency in the rats fed both types of dietary fat. Activity of Δ5-desaturase was also not changed by zinc deficiency
in the rats fed both dietary fats. Levels of fatty acids in liver phospholipids and microsomes derived by Δ4-, Δ5-, and Δ6-desaturation
were not consistently changed by zinc deficiency in the rats fed both types of dietary fat. Thus, the enzyme studies and also
fatty acid composition data of liver phospholipids and microsomes indicate that zinc deficiency does not considerably disturb
desaturation of linoleic and α-linolenic acid. Therefore, it is suggested that similarities between deficiencies of zinc and
essential fatty acids described in literature are not due to disturbed desaturation of linoleic acid in zinc deficiency. The
present study also indicates that zinc deficiency enhances incorporation of eicosapentaenoic acid into phosphatidylcholine
of rats fed diets with large amounts ofn-3 polyunsaturated fatty acids. 相似文献
107.
Main objective of this study was to test the effects of Mg(OH)2-fertilization in a Norway spruce ecosystem showing severe symptoms of Mg-deficiency.The site is characterized by high atmospheric inputs with deposition rates of 1.25 kg H, 42 kg S, and 32 kg N per ha and year. The typic Dystrochrept derived from granite is acidified down to greater depths. The pH-values in soil solution of the organic surface layer and the upper mineral soil are around 3.5. Concentrations of Al, SO4
2-, and especially NO3
- and DOC are very high. The element balance indicates a significant influence of N-inputs and processes of N-turnover on the chemical status of the soil and probably on tree nutrition. Nitrification in the upper mineral soil leads to a transformation of a major part of NH4
+ into NO3
-, which is quantitatively leached, resulting in an ecosystem-internal H+-production of 1.8 keq ha-1yr-1. NO3
- and SO4
2- govern the seepage output from the ecosystem.Mg(OH)2 fertilization resulted in manifold increased Mg2+ concentrations in soil solution down to 70 cm soil depth and to a significant increase of pH down to 25 cm mineral soil depth. Nitrate concentrations were elevated after fertilization, but decreased within 15 months below the level of the control plot. As a mean over the whole experimental period, N-output was not increased by fertilization. Despite an elevated internal proton production due to nitrification, acid buffering in the soil was clearly increased, but enhanced Al-mobilization was not observed. Mg/Al- and Ca/H-ratios in soil solution indicate much more favourable conditions for fine root growth. Fertilization also increased the amount of exchangeable Mg down to 40cm mineral soil depth. Mg contents in current-year needles increased after three vegetation periods. Thirty months after application, only 10% and 4% of the fertilized Mg had left the organic surface layer and the mineral soil with seepage water output, respectively. 相似文献
108.
Koichiro Suzuki Kenji Kanazawa Kyoko Higuchi Naoko K. Nishizawa Satoshi Mori 《Biometals》1997,10(2):77-84
In a previous paper we reported that an acidic 36 kDa peptide is the most strongly induced peptide among several peptides induced by Fe deficiency in barley roots. In this paper, polyclonal antibodies were raised against the 36 kDa peptide. This peptide appeared in the roots of all the graminaceous species tested (barley, rye, wheat, oat, maize, sorghum and rice) in response to Fe deficiency. More of the peptide was found in the roots of graminaceous species which secrete higher amounts of mugineic acids (MAs) under Fe deficient nutrition status. Induction of the 36 kDa peptide was first observed on the third day of Fe deficiency, rising to a maximum value on the seventh day. The trend has a positive correlation with secretion of MAs during Fe deficiency. Further, resupply of Fe resulted in a decrease in peptide production on the second day, reaching a control level on the seventh day. The rate of decrease in peptide production was observed to be slower than that of MA secretion. Other nutrient stresses such as B excess, B deficiency, Cu excess, Cu deficiency, Mn excess, Mn deficiency, Zn excess and Zn deficiency induced far less of the peptide. The specific expression of the 36 kDa peptide in roots of graminaceous species under Fe deficiency suggested the positive association of the peptide with a specific Fe deficiency tolerance mechanism in graminaceous plants. 相似文献
109.
Douglas B. Kintner James H. Fitzpatrick Jr. David D. Gilboe 《Journal of neurochemistry》1997,69(3):1219-1227
Abstract: The Pulsinelli-Brierley four-vessel occlusion model was used to study the consequences of hyperglycemic ischemia and reperfusion. Rats were subjected to either 30 min of normo- or hyperglycemic ischemia or 30 min of normo- or hyperglycemic ischemia followed by 60 min of reperfusion. In some animals, 2 mg/kg BN 50739, a platelet-activating factor receptor antagonist, was administered intraarterially either before or after the ischemic insult. The changes in mitochondrial membrane free fatty acid levels, phosphatidylcholine fatty acyl composition, and thiobarbituric acid-reactive material (TBAR) content plus the mitochondrial respiratory control ratio (RCR) were monitored. When the platelet-activating factor antagonist was present during normoglycemia, (a) the mitochondrial free fatty acid release both during and after ischemia was slowed, (b) reacylation of phosphatidylcholine following ischemia was promoted, and (c) TBAR accumulation during and following ischemia was decreased. The detrimental effects of hyperglycemia were muted when BN 50739 was present during ischemia. The RCR was preserved and phosphatidylcholine hydrolysis during ischemia was decreased. TBAR levels were consistently higher in hyperglycemic brain mitochondria both during and after ischemia. The RCR correlated directly with mitochondrial phosphatidylcholine polyunsaturated fatty acid content during ischemia and reperfusion. BN 50739 protection of mitochondrial membranes in brain may be influenced by tissue pH. 相似文献
110.
Thiamine phosphate esters (thiamine monophosphate-TMP; thiamine diphosphate-TDP and thiamine triphosphate-TTP) were measured as their thiochrome derivatives by High Performance Liquid Chromatography in the brains of pyrithiamine-treated rats at various stages during the development of thiamine deficiency encephalopathy. Severe encephalopathy was accompanied by significant reductions of all three thiamine phosphate esters in brain. Neurological symptoms of thiamine deficiency appeared when brain levels of TMP and TDP fell below 15% of normal values. Activities of the TDP-dependent enzyme -ketoglutarate dehydrogenase were more severely reduced in thalamus compared to cerebral cortex, a less vulnerable brain structure. On the other hand, reductions of TTP, the non-cofactor form of thiamine, occurred to a greater extent in cerebral cortex than thalamus. Early reductions of TDP-dependent enzymes and the ensuing metabolic pertubations such as lactic acidosis impaired brain energy metabolism, and NMDA-receptor mediated excitotoxicity offer rational explanations for the selective vulnerability of brain structures such as thalamus to the deleterious effects of thiamine deficiency. 相似文献