《生物化学教学课件：Lecture 4 The Pentose Phosphate Pathway (HMP) and Gluconeogenesis(糖异生）》由会员分享，可在线阅读，更多相关《生物化学教学课件：Lecture 4 The Pentose Phosphate Pathway (HMP) and Gluconeogenesis(糖异生）（61页珍藏版）》请在金锄头文库上搜索。
1、Lecture 4 The Pentose Phosphate Pathway (HMP) and Gluconeogenesis(糖异生）糖异生） 生物化学教程P371-389 Synthase（合酶）（合酶） and Synthetase（合成酶）（合成酶）; Ligase（连接酶）（连接酶） and Lyase（裂合酶）（裂合酶）; Kinase（激酶）（激酶）, and Phosphatase（磷酸酯酶）（磷酸酯酶）the Names Are Confusing!Synthase 合酶合酶-catalyze condensation reactions （缩合反应）（缩合反应）in w
2、hich no nucleoside triphosphate (ATP, GTP, and so forth) is required as an energy source. e.g. Citrite synthase Synthetase 合成酶合成酶-catalyze condensations that do use ATP or another nucleoside triphosphate as a source of energy for the synthetic reaction. Succinyl-CoA synthetaseLigases 连接酶连接酶-(from th
3、e Latin ligare, “to tie together”) are enzymes that catalyze condensation reactions in which two atoms are joined using ATP or another energy source. (Thus synthetase are ligases.) lyase裂合酶裂合酶,裂解酶裂解酶 -enzymes that catalyze cleavages (or, in the reverse direction, additions) in which electronic rearr
4、angements occur. e.g. The PDH (pyruvate dehydrogenase) complex,Kinase- is applied to enzymes that transfer a phosphoryl group from a nucleoside triphosphate such as ATP to an acceptore.g. hexokinase, glucokinase, glycogen phosphorylase kinase, pyruvate kinasephosphatase 磷酸（酯）酶磷酸（酯）酶dephosphorolysis,
5、 the removal of a phosphoryl group from a phosphate ester with water as the attacking species.e.g. Fructose bisphosphatase-1 （果糖-二磷酸酶-1） converts fructose 1,6-bisphosphate to fructose 6-phosphate in gluconeogenesisFructose bisphosphatase-1 pentose phosphate pathwayisanimportantpathwayforgeneratingNA
6、DPH(forbiosyntheticreactions)pentosesugars(fornucleotidebiosynthesis)Variant of pathway functions in plants to fix carbon in photosynthesisinthecytosolseveralpossiblebranchesthatcanbetakentoallowittosupplythecellwithdifferentproductsasneeded.重点重点Ribose-5-phosphate（核糖-5-磷酸）：fornucleicacidsynthesise.g
7、.RNA,DNA,NAD+,FAD,ATP,CoANADH VS NADPHNADH :donateselectronstotheelectron transportsystemforenergygeneration氧化途径（分解代谢分解代谢）中电子供体NADPH:donateselectronstobiosyntheticreactions还原途径（合成代谢合成代谢）电子供体6-Phosphogluconolactone 6-磷酸葡萄糖酸磷酸葡萄糖酸- -内酯内酯6-Phosphogluconate 6-磷酸葡萄糖酸磷酸葡萄糖酸Ribulose-5-Phosphate 核酮糖核酮糖-5-磷酸
8、磷酸Ribose-5-Phosphate 核糖核糖-5-磷酸磷酸Xylulose-5-Phosphate 木酮糖木酮糖-5-磷酸磷酸Glyceraldehyde-3-Phosphate 甘油醛甘油醛-3-磷酸磷酸Sedoheptulose-7-Phosphate 景天庚酮糖景天庚酮糖-7-磷酸磷酸Erythrose-4-Phosphate 赤藓糖赤藓糖-4-磷酸磷酸Fructose-6-Phosphate 果糖果糖-6-磷酸磷酸1. The Oxidative Phase: Generation of Reducing Power as NADPHG6P脱氢酶脱氢酶内酯酶内酯酶6-磷酸葡萄糖酸
9、磷酸葡萄糖酸- -内酯内酯6-磷酸葡萄糖酸磷酸葡萄糖酸5-磷酸核酮糖磷酸核酮糖6-P-G酸脱氢酶酸脱氢酶2. The Nonoxidative Phase: Alternative Fates of Pentose Phosphates木酮糖的C3位羟基才能满足转酮酶的要求核酮糖的C3位羟基不能满足转酮酶的要求5-磷酸核酮糖磷酸核酮糖5-磷酸木酮糖磷酸木酮糖5-磷酸核糖磷酸核糖磷酸戊糖异构酶磷酸戊糖异构酶磷酸戊糖差向酶磷酸戊糖差向酶转酮酶转酮酶转醛酶转醛酶木酮糖木酮糖-5-P核糖核糖-5-P甘油醛甘油醛-3-P景天庚酮糖景天庚酮糖-7-P果糖果糖-6-P景天庚酮糖景天庚酮糖-7-P甘油醛甘油醛
10、-3-P赤藓糖赤藓糖-4-PHMP途径与糖酵解途径相连途径与糖酵解途径相连使得机体内的使得机体内的NADPH、ATP、核糖、核糖-5-磷酸，丙酮酸等物质可根据需要保持合理磷酸，丙酮酸等物质可根据需要保持合理的水平的水平F6PG6PPhosphoglucoseisomerase转酮酶转酮酶赤藓糖赤藓糖-4-P木酮糖木酮糖-5-P甘油醛甘油醛-3-P果糖果糖-6-P异构酶异构酶重点重点The whole reactions重点重点5-磷酸核酮糖磷酸核酮糖核糖核糖-5-P木酮糖木酮糖-5-P重点重点转醛酶转醛酶转酮酶转酮酶果糖果糖-6-P木酮糖木酮糖-5-P核糖核糖-5-P甘油醛甘油醛-3-P景天庚
11、酮糖景天庚酮糖-7-P景天庚酮糖景天庚酮糖-7-P甘油醛甘油醛-3-P赤藓糖赤藓糖-4-P重点重点转酮酶转酮酶木酮糖木酮糖-5-P赤藓糖赤藓糖-4-P甘油醛甘油醛-3-P果糖果糖-6-P重点重点6-磷酸葡萄糖酸磷酸葡萄糖酸6G6P7H2O12NADP5G6P6CO212NADPH12HPioutline重点重点TailoringthePentosePhosphatePathwaytoSpecificNeeds1.Whennucleotidebiosynthesisisneeded,ribose-5-phosphateistheprimaryproduct.2.WhenNADPHisneeded
12、,cyclingoffructoseandglucosephosphatesisfavored3.Whenenergyistheprimaryneed,glycolysisandcitricacidcycleintermediatesarefavoredproducts.重点重点G6PDH（Glucose-6-phosphatedehydrogenase）Glucose-6-Phosphate +NADP+ 6-Phosphogluconolactone + NADPH In the absence of sufficient NADPH, glutathione remains oxidiz
13、ed and peroxides cannot be neutralized.Human Genetic Disorders Involving HMP Enzymes重点重点6-P-G内酯内酯Eg. Red cell - GSH维持维持Pr结构完整性结构完整性保护脂膜不被过氧化物氧化保护脂膜不被过氧化物氧化维持血红素的维持血红素的Fe 2（因（因Fe 3无运输氧的功能）无运输氧的功能）查阅查阅Glucose-6-phosphate dehydrogenase deficiency相关论文，写相关论文，写800字左右小论文字左右小论文介绍一下该基因具体信息，该病发生原因，介绍一下该基因具体信息
14、，该病发生原因，危害性及治疗措施。下节课课前交。危害性及治疗措施。下节课课前交。Gluconeogenesis 葡糖异生作用 p3802008/3/27Gluconeogenesis（糖异生）isthesynthesisofglucosefromnon-carbohydrateprecursors.Glucosestoresaredepletedduringperiodsofstarvationorfasting（禁食）beyondaday.Sincethebrainreliesonglucose(120g/d)asasourceofenergy.PYRUVATEGLUCOSEGluconeo
15、genesis（糖异生）PYRUVATE GLUCOSEAny molecule that can be converted to pyruvate is considered glucogenic.Lactate and alanine are glucogenic.Glycerol is also glucogenic.重点重点Lactate and alanine are glucogenicIn muscle alanine is produced from pyruvate by transamination.pyruvate + glutamate alanine + -ketog
16、lutarateIn the liver alanine is converted back to pyruvate.In active muscle lactate builds up, passes through the blood and is converted to pyruvate in the liver.Thus, part of the metabolic burden of active muscle is shifted to the liver.The Cori CycleLactate from active muscle is converted to gluco
17、se in liver重点重点Carl and Gerty CoriNobel Prize in Physiology and medicine1947“for their discovery of the course of the catalytic conversion of glycogen” Gluconeogenesis: Pyruvate GlucoseThe enzymes in red belong to the gluconeogenic（糖异生）（糖异生） pathway. The enzymes in blue are held in common between th
18、e two pathways.GluconeogenesisThe irreversible glycolytic enzymes are: hexokinase（己糖激酶（己糖激酶） (G =-8 kcal mol-1) phosphofructokinase（磷酸果糖激酶（磷酸果糖激酶） (G = -5.3 kcal mol-1 ) pyruvate kinase（丙酮酸激酶）（丙酮酸激酶） (G = -4.0 kcal mol-1)The enzymes of gluconeogenesis are:pyruvate carboxylase (ATP) 丙酮酸羧化酶丙酮酸羧化酶phosp
19、hoenolpyruvate carboxykinase (GTP) PEP羧激酶羧激酶 fructose 1,6-bisphosphatase（果糖（果糖-1，6-二磷酸酶）二磷酸酶） glucose 6-phosphatase （G-6-P酶）酶）重点重点Pyruvate CarboxylasePyruvate + CO2 + ATP + H2O oxaloacetate + ADP + Pi + 2 H+Pyruvate Carboxylase fixes CO2Require the cofactor BIOTIN. Biotin is a vitamin and is always
20、involved in CO2 fixation.In the mitochondrial matrix重点重点丙酮酸羧化酶丙酮酸羧化酶Biotin噻吩环和尿素结合而成的一个双环化合物Phosphoenolpyruvate CarboxykinasePEP羧激酶Oxaloacetate + GTP phosphoenolpyruvate + GDP + CO2in the cytosol or mitPEP is now synthesized and the sum of the two reaction is: Pyruvate + ATP + GTP + H2O PEP + ADP +
21、GDP + Pi + H+.重点重点Pyruvate is carboxylated in mitPyruvate CarboxylaseOxaloacetate cant pass out of the mit Oxaloacetate decarboxylated andphosphorylated in the cytosol or mit.Phosphoenolpyruvate Carboxykinase（羧激激酶）重点重点丙酮酸羧化酶丙酮酸羧化酶Fructose 1,6-bisphosphatasefructose 1,6-bisphosphate + H2O 6-P-F + Pia
22、n allosteric enzyme and regulates gluconeogenesis.6-P-F is easily converted to 6-P-G.重点重点（果糖（果糖-1，6-二磷酸酶）二磷酸酶）果糖二磷酸酶2pi果糖激酶-2Pi化受抑制重点重点Effect of glucagon on liver glycolysisGlucose 6-phosphatase glucose 6-phosphate + H2O glucose + PiLiver can send glucose to blood to maintain homeostasisGlucose 6-ph
23、osphate is also a precursor to glycogen.重点重点（G-6-P酶）酶）自我平衡糖原generation of glucose from glucose 6-phosphateendoplasmic reticulum (ER) proteinsGlucose 6-phosphatase is stabilized by a Ca2+-binding protein (SP)重点重点Gluconeogenesis Stoichiometry 2pyruvate + 4ATP + 2GTP + 2NADH + 6H2O glucose + 4ADP + 2GD
24、P +6Pi +2NAD+ + 2H+; G = -9kcal mol-1. it takes 6 nucleotide triphosphate molecules to synthesize glucose. Only 2 nucleotide triphosphate molecules are generated from glycolysis.重点重点Carbohydrate synthesis from simple precursors. The pathway from PEP to 6-P-G is common to the biosynthetic conversion
25、of many different precursors of carbohydrates in animals and plants. Plants and photosynthetic bacteria are uniquely able to convert CO2 to carbohydrates.Gluconeogenesis ends at glucose 6-PGlucose 6-P is valuable; a precursor for glycogen synthesis.Glucose 6-phosphatase is present only in tissues re
26、sponsible for maintaining blood glucose levels, liver and kidney.In liver, glucose 6-phosphatase is highly regulated.Glycolysis and gluconeogenesis are reciprocally regulatedA high AMP indicates that the energy charge is low and signals the need for ATP.High ATP and citrate indicate the energy charg
27、e is high and intermediates are abundant.Glucagon stimulatesInsulin stimulatesInsulin stimulates the expression of phosphofructokinase（磷酸果糖激酶）, pyruvate kinase（丙酮酸激酶）, Glucagon inhibits the expression of these enzymes and stimulates instead the production of two key gluconeogenic enzymes, phosphoeno
28、lpyruvate carboxykinase（PEP羧激酶）and fructose 1,6-bisphosphatase（果糖-1，6-二磷酸酶）. Transcriptional control in eukaryotes hours or days 重点重点The Promoter of the Phosphoenolpyruvate Carboxykinase（PEP羧激酶）regulatory sequences (response elements) IRE：insulin response element GRE：glucocorticoid糖(肾上腺)皮质激素response
29、 element TRE： thyroid hormone甲状腺素 response element CREI and CREII：cAMP response elements.Cooperation between Glycolysis and Gluconeogenesis. in a tissue-specific fashion思考题：思考题：1.什么是糖异生？详述糖异生的过程。并比较该过程与什么是糖异生？详述糖异生的过程。并比较该过程与糖酵解有何差异？糖酵解有何差异？2.What is the cost (in ATP equivalents) of transforming glucose to pyruvate via glycolysis and back again toglucose via gluconeogenesis?3. 2，6-二磷酸果糖如何调控糖异生和糖酵解的？二磷酸果糖如何调控糖异生和糖酵解的？4.什么是什么是HMP途径？途径？HMP有何生理意义？有何生理意义？5.什么是什么是Cori循环？循环？
