Chapter 6 Carbohydrate Metabolism

Lecture 1 Function of carbohydrate Lecture 2 The classification of carbohydrates Lecture 3 Glycolysis Lecture 4 The fates of pyruvate Lecture 5 Gluconeogenesis Lecture 6 The pentose phosphate pathway of glucose oxidation Lecture 7 Citric acid cycle

Lecture 5 Gluconeogenesis Chapter 12

1 Gluconeogenesis Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. Gluconeogenesis occurs in all animals, plants, fungi, and microorganisms. The reactions are essentially the same in all tissues and all species.

Gluconeogenesis and glycolysis are not identical pathways running in opposite directions, they do share several steps. Three reactions of glycolysis are essentially irreversible in vivo and cannot be used in gluconeogenesis.

In gluconeogenesis, the three irreversible steps are bypassed by a separate set of enzymes, catalyzing reactions that are sufficiently exergonic to be effectively irreversible in the direction of glucose synthesis.

Pyruvate → Phosphoenolpyruvate Conversion of pyruvate to phosphoenolpyruvate requires two exergonic reactions.

Fructose 1,6-Bisphosphate to Fructose6-Phosphate + Pi 1,6-二磷酸果糖酶

Glucose 6-Phosphate to Glucose glucose-6-phosphatase 6-磷酸葡萄糖酶

Gluconeogenesis is energetically expensive, but essential.

2. Regulation of Gluconeogenesis

Lecture 6 The pentose phosphate pathway of glucose oxidation 戊糖磷酸途径

The pentose phosphate pathway (PPP, also called the phosphogluconate pathway and the hexose monophosphate shunt ) is a process that generates NADPH and pentoses (5-carbon sugars). The pentose phosphate pathway (also called the phosphogluconate pathway 【磷酸葡萄糖酸途径】 and the hexose monophosphate shunt 【己糖磷酸支路HMP 】) is a process that generates NADPH and pentoses 【戊糖】(5-carbon sugars).途径：分两个阶段 氧化反应阶段：生成NADPH及CO2 非氧化反应阶段：磷酸已糖的再生(一系列基团的转移)

There are two distinct phases in the pathway There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars. The pentose phosphate pathway (also called the phosphogluconate pathway 【磷酸葡萄糖酸途径】 and the hexose monophosphate shunt 【己糖磷酸支路HMP 】) is a process that generates NADPH and pentoses 【戊糖】(5-carbon sugars).途径：分两个阶段 氧化反应阶段：生成NADPH及CO2 非氧化反应阶段：磷酸已糖的再生(一系列基团的转移)

1 The reactions of the pentose phosphate pathway The oxidative phase produces pentose phosphates and NADPH Oxidative reactions that convert glucose 6-phosphate into ribulose 5-phosphate, generating two NADPH molecules.

glucose-6-phosphate dehydrogenase 6-phosphogluconate 磷酸葡萄糖脱氢酶 6-phosphogluconate 磷酸葡萄糖酸脱氢酶 G 6-P+ 2NADP+ H2O ribulose 5-phosphate + CO2 + 2NADPH + 2H

G6P → Ribulose 5-phosphate + CO2 NADP+ NADPH+H+ G6P → Ribulose 5-phosphate + CO2 NADP+ NADPH+ H+ 6 G6P 6H2O+6CO2

The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate 6 ribulose 5-phosphate isomerase transketolase transaldolase 5 glucose-6-phosphate 5-磷酸核酮糖,6-磷酸葡萄糖 isomerase－异构化 transketolase－转酮基 transaldolase－转醛基

Who control Glucose enters Glycolysis or the Pentose Phosphate Pathway? Whether glucose 6-phosphate enters glycolysis or the phosphate pathway depends on the current needs of the cell and on the concentration of NADP in cytosol.

Lecture 7 Citric acid cycle Chapter 13

Citric acid cycle, also called the tricarboxylic acid cycle or the Krebs cycle. The citric acid cycle is the final common pathway for the oxidation of fuel molecules—amino acids, fatty acids, and carbohydrates. the tricarboxylic acid (三羧酸循环) cycle Hans Krebs, 1900–1981

Stage 1: oxidation of fatty acids, glucose, and some amino acids yields acetyl-CoA. Stage 2: oxidation of acetyl groups in the citric acid cycle includes four steps in which electrons are abstracted.

Tricarboxylic acid cycle，TCA A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. acetyl group【乙酰基】乙酰CoA与OAA缩合形成柠檬酸，再经一系列氧化、脱羧反应，重新形成OAA的循环过程。乙酰CoA在该循环中被彻底氧化分解成CO2和H2O，并产生能量。

1 Reactions of the Citric acid cycle

(1) Formation of Citrate Citrate (6C) is formed from the irreversible condensation of acetyl CoA (2C) and oxaloacetate (4C)- catalyzed by citrate synthase. Citrate【柠檬酸】

FIGURE 16–8 Structure of citrate synthase.

(2) Formation of Isocitrate via cis-aconitate Citrate is converted to isocitrate by an isomerization catalyzed by aconitase. This is actually a two step reaction during which cis-aconitate is formed as an intermediate. It is the cis-aconitate which gives the enzyme its name.

(3) Oxidation of Isocitrate to α- Ketoglutarate and CO2 Citrate is converted to isocitrate by an isomerization catalyzed by aconitase. This is actually a two step reaction during which cis-aconitate is formed as an intermediate. It is the cis-aconitate which gives the enzyme its name.第一次脱氢、脱羧 TCA循环的分界点，三羧酸→二羧酸

(4) Oxidation of α-Ketoglutarate to Succinyl -CoA and CO2 α-Ketoglutarate is oxidized to succinyl CoA (4C) and CO2 by the α-ketoglutarate dehydrogenase complex. Like pyruvate dehydrogenase, this is a complex of three enzymes and uses NAD+ as cofactor.第二次脱羧、脱氢,产生NADH及CO2各一份

(5) Conversion of Succinyl-CoA to Succinate 【琥珀酸】Succinyl CoA (4C) is converted to succinate by Succinyl CoA synthetase. The reaction uses the energy released by cleavage of the Succinyl-CoA bond to synthesize either GTP (mainly in animals) or ATP (exclusively in plants) from Pi and, respectively GDP or ADP. TCA循环中唯一底物水平磷酸化 GTP + ADP → GDP + ATP

(6) Oxidation of Succinate to Fumarate Succinate is oxidized to fumarate (4C) by succinate dehydrogenase. FAD is tightly bound to the enzyme and is reduced to produced FADH2.第三次脱氢 脱氢酶的辅酶为FAD

(7) Hydration of Fumarate to Malate Fumarate is converted to malate by fumarase; this is a hydration reaction required the addition of a water molecule.

(8) Oxidation of Malate to Oxaloacetate Malate is oxidized to oxaloacetate (4C) by malate dehydrogenase. NAD+ is again required by the enzyme as a cofactor to accept the free pair of electrons and produced NADH. 第四次脱氢

The Energy of Oxidations in the Cycle Is Efficiently Conserved Calculate the overall yield of ATP from the complete oxidation of glucose.

3(NADH)x2.5 + (FADH2)x1.5 + 1(ATP/GTP) = 10ATP

Acetyl-CoA enters the citric acid cycle (in the mitochondria of eukaryotes, the cytosol of prokaryotes) as citrate synthase catalyzes its condensation with oxaloacetate to form citrate. For each acetyl-CoA oxidized by the citric acid cycle, the energy gain consists of three molecules of NADH, one FADH2, and one nucleoside triphosphate (either ATP or GTP).

The net reaction for the TCA is as follows： In eight sequential reactions, including two decarboxylations, the citric acid cycle converts citrate to oxaloacetate and releases two CO2. The net reaction for the TCA is as follows： CH3COSCoA+3NAD++FAD+ADP/GDP+Pi+2H2O →2CO2+3NADH+3H++FADH2+ATP/GTP+CoASH

Regulation of the TCA Cycle The citric acid cycle is regulated at its three exergonic steps Those catalyzed by citrate synthase, isocitrate dehydrogenase, and -ketoglutarate dehydrogenase —can become the rate-limiting step under some circumstances.

Anaplerotic Reactions Replenish Citric Acid Cycle Intermediates As intermediates of the citric acid cycle are removed to serve as biosynthetic precursors, they are replenished by anaplerotic reactions