当前位置:首页 >> 学科竞赛 >>

高中生物奥赛辅导生化——三羧酸循环


3. Aerobic catalysis of carbohydrate and tricarboxylic acid cycle 第三节 糖的有氧分解与三羧酸循环

丙酮酸脱羧,乙酰辅酶A的氧化 均发生在线粒体的基质。

ATP的合成在线粒体的内膜上进行的

3.1 A survey of introduction

概述

? 三羧酸循环( Tricarboxylic acid cycle) TCA Cycle ? Kreb’s循环( Kreb’s cycle) ? 柠檬酸循环(Citric cycle)

3.1.1 葡萄糖的有氧分解包括三个部分
Glucose

Glycolysis Yielding of acetyl-CoA

Ⅰ Ⅱ
NAD+ NADH +H+

Pyruvate

CoA-SH CO2

Acetal-CoA TCA Cycle

acetyl-CoA is oxidized



CO2 + H2O

3.1.2 三羧酸循环的研究简史
The Nobel Prize in Physiology or Medicine 1953

"for his discovery of the citric acid cycle"

Pyruvate is oxidized and acetate is transferred to CoA.
Acetyl CoA enters the TCA cycle. Acetate is oxidized to CO2.

Pyruvate is oxidized and acetate is transferred to CoA.
Acetyl CoA enters the TCA cycle. Acetate is oxidized to CO2.

Pyruvate is oxidized and acetate is transferred to CoA.
Acetyl CoA enters the TCA cycle. Acetate is oxidized to CO2.

3.2 Pyruvate is oxidized to acetyl-CoA
? Pyruvate is transported into mitochondria(线粒体)

then oxidized to acetyl-CoA (releasing CO2) before
entering the citric acid cycle

丙酮酸脱氢酶系

Regulation of pyruvate dehydrogenase complex

砷化物对机体的毒害不仅限于糖酵解,它与丙酮酸

脱氢酶复合物中E2辅基硫辛酰胺的巯基发生共价结合,
使还原型硫辛酰胺形成失去催化能力的砷化物。

3.3 Tricarboxylic Acid Cycle
3.3.1 Reaction process of tricarboxylic acid cycle (三羧酸循环,柠檬酸循环)
乙酰CoA 草酰乙酸 柠檬酸 顺乌头酸 异柠檬酸

苹果酸 延胡索酸 a-酮戊二酸 琥珀酸

琥珀酰CoA

乙酰CoA 草酰乙酸 柠檬酸

苹果酸

顺乌头酸

异柠檬酸 延胡索酸

琥珀酸

a-酮戊二酸

琥珀酰CoA

3.3.1.1 The cycle begins with the condensation of acetyleCoA and oxaloacetate to form citrate
柠檬酸合酶

草酰乙酸

柠檬酸

The hydrolysis the high energy thioester(硫酯) drives the reaction.

合酶与合成酶

? 合酶 (synthase):
– 催化加合反应,促使合成

? 合成酶 (synthetase):
– 催化连接反应,一般需要NTP

3.3.1.2 Citrate isomerizes to isocitrate (异柠檬酸) via cis-aconitate (顺乌头酸)

Aconitase (乌头酸酶)
* * * * * *

90%

4%

6%

?G0’ = 8.4 kJ/mol

?G0’ = -2.1 kJ/mol

Fluoride citrate(氟柠檬酸) is the special inhbitor of aconitase

3.3.1.2 Citrate isomerizes to isocitrate via cis-aconitate

酶活性中心的 只能结合底物的 一部分,底物的部 分具有手性,分子 局部的手性,即 分子的前手性.

前手性、潜手性(pro-chiral)

3.3.1.3 Isocitrate undergoes oxidative decarboxylation (氧化脱羧) to form a-ketoglutarate (a-酮戊二酸)
异柠檬酸脱氢酶
* * * *

Reaction 4 and 5

Isocitrate is oxidized (第一次脱氢) and decarboxylated.(第一次脱羧)

3.3.1.4 a-ketoglutarate undergoes oxidative decarboyxlation to form succinyl-CoA (琥珀酰CoA)

a-酮戊二酸脱氢酶系

*

*

*

*

第二次脱氢,第二次脱羧.E1酶不受磷酸共价调节. Reaction requires TPP and lipoate etc(6种辅酶).

3.3.1.5 Cleavage of the thioester bond (硫酯键) in succinylCoA is coupled to GTP (or ATP) formation

*

*

琥珀酰CoA

琥珀酰CoA合成酶 (也称琥珀酸硫激酶)

琥珀酸

The third example of substrate-level phosphorylation. 琥珀酸是对称分子,没有了手性.

3.3.1.6 Succinate is oxidized to fumarate (延胡索酸) 琥珀酸脱氢酶

立体异构体 马来酸

琥珀酸

延胡索酸

The free energy change of this reaction is insufficient to reduce NAD+. Succinate Dehydrogenase is directly linked with the electron transport chain.

3.3.1.6 Succinate is oxidized to fumarate (延胡索酸) 1. The enzyme catalyzes stereospecific dehydrogenation 2. Malonate (丙二酸) is the inhibitor of the reaction

丙二酸

琥珀酸(丁二酸)

3.3.1.7 Fumarate is hydrated to L-malate (苹果酸) 延胡索酸酶

延胡索酸

苹果酸

Hydration(水合)

3.3.1.8 Oxaloacetate (草酰乙酸) is regenerated by the oxidation of L-malate (苹果酸)
苹果酸脱氢酶

* *

or
*
*

The standard free energy of this reaction is very positive. The oxidation of malate is driven by the efficient removal of the products.

The last three reactions of the of the TCA cycle The last three reactions of the of the TCA cycle are similar to fatty acid degradation and synthesis, and some amino acid degradations. oxidation – hydration – oxidation.

A methylene group (CH2) is converted to a carbonyl group (C=O).

The citric acid cycle was confirmed to be universal in cells TCA循环被证明在细胞中是广泛存在的

? Details worked out by studying highly purified enzymes of the cycle in vitro;

使用高度提纯的酶在体外实验证明了这一代谢途径
? Also by isotope tracer experiments in vivo; 通过体内同位素示踪法也证明了这一代谢途径

3.3.2 Survey of TCA cycle
1. 总反应式:
O CH3-C-SCoA + 3NAD+ + FAD + GDP + Pi 2CO2 + 3NADH?H+ + 1FADH2 + 1GTP + CoA-SH 2. There are two carbon atoms in the form of acetyl-SCoA enters every cycle; and there are two decarboxylations take place in each cycle; 乙酰辅酶A中的二碳乙酰基进入TCA循环;在循环中发生 两次脱羧反应. Notice: the 2 carbon atoms entering the cycle are not the same as those leaving the cycle

3.3.2 Survey of TCA cycle

3. There are four dehydrogenation reactions take place in each cycle;
在循环中发生四次脱氢反应(3NADH,1FADH2)

4. There is a substrate level phosphoralation; 循环中发生一次底物水平磷酸化

3.3.2 Survey of TCA cycle
5. The reactions catalyzed by aconitase and fumarase is asymmetry reactions;

顺乌头酸酶和延胡索酸酶等催化非对称反应

6. All of the intermediary metabolisms are not
synthesis and decomposition net. 所有中间代谢产物在代谢中没有净合成或净降解.

3.4 The energetic of the aerobic decomposition of glucose 葡萄糖有氧分解途径的能量计算
1. Acetyl in acetyl-S-CoA was oxydized: 化学氧化释放的自由能:874.9 kJ/mol 生物氧化释放的自由能:520.9 kJ/mol 用于ATP合成的自由能:354 kJ/mol

354 ? 40.5% 874 .9

3.4 The energetic of the aerobic decomposition of glucose
2. Hydrations in TCA-cycle:
H 2O

The third H2O entered in TCA cycle:
Citryl-CoA+H20 succinyl-CoA + H2O Fumarate+H20

H 2O
Citrate+ CoA-SH

Succidate + CoA-SH Matalte
H 2O

3.4 The energetic of the aerobic decomposition of glucose
3. Dehydrogenations in oxydation of glucose:
In EMP: In formation of acetyl-CoA: In TCA cycle: C6H12O6 2×pyruvate 2 × CoA-SH 2×pyruvate + 4H 2×acetyl-CoA + 4H +2CO2 16H + 4CO2 2 × CoA-SH

2×acetyl-CoA + 2× 3 H2O

So:

C6H12O6 + 6H2O 24H + 6 CO2 6O2 12H2O C6H12O6 + 6O2 6H2O + 6 CO2

3.4 The energetic of the aerobic decomposition of glucose
4. Caculation of energy
Numbers of ATP

In EMP: In formation of acetyl-CoA:

ATP 4-2 2NADH?H+(→FADH2) 2 × 2.5 (2 ×1.5 ) 2NADH?H+ 3NADH?H+ × 2 2 × 2.5 3 × 2.5 × 2 1 × 1.5 × 2 1×1×2 32 (30)

In TCA cycle:

FADH2 × 2 GTP × 2

Summery:

3.5 TCA环的生理意义
1. All organic chemicals can be completely

oxidized to CO2 and H2O via a cycled pathway;
所有的有机化合物都可以通过TCA环彻底降解为

CO2 和 H2O ;
2. Plenty energy can be provided accompany the

cycled pathway;
伴随着这一循环途径,大量的自由能被转换;

3.5 TCA环的生理意义

3. The intermediates in the cycle are important sources for biosynthetic precursors;

TCA环中的中间代谢产物是重要的生物合成的前体
4. The cycle is an amphibolic pathway, and is a metabolic hinge of all biochemicals TCA环是一个分解合成无定向途径,是所有生物化

合物的代谢枢纽。分解产能,合成前体.

厌氧细菌(anaerobic bacteria)中 TCA环是中断的
? They lack the a-keto—glutarate dehydrogenase; 厌氧菌缺乏a-酮戊二酸脱氢酶 ? Precursors are provided for the synthesis of amino acids, nucleotides, heme etc. 合成代谢的前体通过正向或逆向反 应合成 ? Use an incomplete citric acid cycle as a source, not of energy, but of biosynthetic precursors.

TCA 循 环 在 合 成 代 谢 中 的 作 用
卟啉

合成其他物质的前体,必然导致草酰乙酸等浓度的降低,这 使得乙酰CoA的受体大大减少,从而使TCA循环效率降低.

3.6 Reactions that replenish citric acid cycle intermediates – anaplerotic reactions (TCA环的回补)

增加草酰乙酸及苹果酸的数量

丙酮酸羧化支路
PEP
CO2 GDP GTP

Pyruvate
CO2 + ATP ADP + Pi

acetyl-CoA

oxaloacetate
NADH+H+

Citrate

NAD+

malate
NADPH

Pyruvate

Role of biotin (生物素) in the pyruvate carboxylase reaction

3.7 TCA Cycle Regulation (TCA循环的调节)
? In addition to generating reducing potential, the TCA cycle also provides molecules for biosynthetic pathways.
? Also, the TCA cycle is an entry point for degradative pathways such as amino acid catabolism.

? Thus, the TCA cycle is highly regulated.

TCA Cycle: It ain’t just ATP.

3.8 乙醛酸循环(Glyoxylate Cycle)
微生物和植物可以在产乙酸或产

P159

生 acetyl CoA 的化合物中生长,因为
它们存在两种酶:异柠檬酸裂解酶 ( isocitrate lyase ) 和 苹 果 酸 合 酶

(malate synthase),这样可使TCA
循环中的异柠檬酸不经脱羧而被裂解 酶裂解为琥珀酸和乙醛酸,乙醛酸与 另一分子 acetyl-CoA 在苹果酸合酶作 用下缩合形成苹果酸。

3.8 乙醛酸循环(Glyoxylate Cycle)
异柠檬酸裂解酶(isocitrate lyase)

+
乙醛酸

苹果酸合酶(malate synthase)
+

+ CoA

乙 醛 酸

(Glyoxylate)

苹果酸合酶 异柠檬酸裂解酶

循 环

乙醛酸

琥珀酸的大量合成

Glyoxylate Cycle

乙醛酸循环体

天冬氨酸

乙 醛 酸 循 环 和 循 环 的 关 系

TCA

线粒体

胞液

乙醛酸循环体

意义: 乙醛酸循环在植物种子中将种子贮存的三酰 甘油通过乙酰-CoA转变成葡萄糖.


相关文章:
历年高中竞赛生物化学试题汇编
高中生物联赛辅导--历年试题选讲--生物化学 2010.11 注:1、为了方便大家查阅,...2008 年 71.下列哪一生化代谢途径是发生在厌氧环境中 A.三羧酸循环 B.线粒...
高中生物竞赛辅导资料
高中生物竞赛辅导资料_高二理化生_理化生_高中教育_...从而引起胞内一系列生理生化变化,最终表现为细胞整体...线粒 体中催化三羧酸循环、脂肪酸和丙酮酸氧化等...
08年至12年生物奥赛原题——细胞生化分类
近五年,生物联赛决赛细胞生化分类整理 2013 高二生物奥赛辅导阶段测试(一) 1、癌...大部分正常组织的细胞可以进行分裂、传代,但传代次数有限 19.三羧酸循环是物质...
生化试题及答案2
生化试题及答案2_生物学_自然科学_专业资料。一、填空题 2.蛋白质分子表面的_...15.三羧酸循环过程的限速酶_柠檬酸合酶__、_异柠檬酸脱氢酶 、_a—酮戊二...
生化各思考题
生化各思考题_生物学_自然科学_专业资料。第七章、代谢调控 1、什么是新陈代谢...代谢途径 (酶或酶系) 细胞内分布 糖酵解 三羧酸循环 磷酸戊糖途径 糖异生...
生化滴作业
生化滴作业_生物学_自然科学_专业资料。问答题 1、何谓三羧酸循环?它有何特点和生物学意义? 2、磷酸戊糖途径有何特点?其生物学意义何在? 3、何谓糖酵解?糖...
2011全国高中生物奥赛真题
(绝密)高中生物竞赛辅导 64页 免费 2011全国中学生物奥赛真题 11页 免费 生物奥赛...大部分正常组织的细胞可以进行分裂、传代,但传代次数有限 11.三羧酸循环是物...
高中生物奥林匹克竞赛辅导 呼吸作用习题
高中生物奥林匹克竞赛辅导 呼吸作用习题_学科竞赛_高中教育_教育专区。生物奥赛辅导...细胞中物质分解代谢时,三羧酸循环发生在 () A.细胞质 B.细胞核 C.叶绿体 ...
生化简答论述(XX终版)
① 底物浓度:在生化反应中,若酶的浓度为定值,底物的起始浓度较低时,酶促反应...的生物合成也有重要意义 3.在植物体内,三羧酸循环中有机酸的形成,既是生物...
更多相关标签:
生物奥赛辅导 | 高中生物三羧酸循环 | 信息学奥赛辅导 | 数学奥赛辅导丛书 | 高中数学奥赛辅导总结 | 高考奥赛对接辅导 | 信息学奥赛辅导教程 | 数学奥赛辅导丛书pdf |