Chapter 6 Carbohydrate Metabolism Lecture 1 Lecture 2

Chapter 6 Carbohydrate Metabolism

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

Lecture 5 Gluconeogenesis Chapter 12

1 Gluconeogenesis n n Gluconeogenesis is a metabolic pathway that results in the generation of glucose from noncarbohydrate 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.

n n 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.

n 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 n Conversion of pyruvate to phosphoenolpyruvate requires two exergonic reactions.

Fructose 1, 6 -Bisphosphate to Fructose 6 Phosphate + H 2 O + Pi

Glucose 6 -Phosphate to Glucose

n Gluconeogenesis is energetically expensive, but essential.

2. Regulation of Gluconeogenesis

Lecture 6 The pentose phosphate pathway of glucose oxidation

n 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).

n 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.

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

glucose-6 -phosphate dehydrogenase G 6 -P+ 2 NADP+ H 2 O 6 -phosphogluconate dehydrogenase ribulose 5 -phosphate + CO 2 + 2 NADPH + 2 H

6 NADP+ 6 G 6 P 6 NADPH+H+ → 6 NADP+ G 6 P 6 Ribulose 5 -phosphate +6 CO 2 + NADPH+ H 6 6 6 H 2 O+6 CO 2

The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6 -Phosphate 6 ribulose 5 -phosphate isomerase transketolase transaldolase 5 glucose-6 -phosphate

Who control Glucose enters Glycolysis or the Pentose Phosphate Pathway? n 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

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

Stage 1: oxidation of fatty acids, glucose, and some amino acids yields acetyl. Co. A. 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 CO 2 and four pairs of electrons are transferred to coenzymes.

1 Reactions of the Citric acid cycle

(1) Formation of Citrate (6 C) is formed from the irreversible condensation of acetyl Co. A (2 C) and oxaloacetate (4 C)- catalyzed by citrate synthase.

FIGURE 16– 8 Structure of citrate synthase.

(2) Formation of Isocitrate via cis-aconitate

(3) Oxidation of Isocitrate to α- Ketoglutarate and CO 2

(4) Oxidation of α-Ketoglutarate to Succinyl -Co. A and CO 2

(5) Conversion of Succinyl-Co. A to Succinate GTP + ADP → GDP + ATP

(6) Oxidation of Succinate to Fumarate

(7) Hydration of Fumarate to Malate

(8) Oxidation of Malate to Oxaloacetate

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

3(NADH)x 2. 5 + (FADH 2)x 1. 5 + 1(ATP/GTP) = 10 ATP

n Acetyl-Co. A 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. n For each acetyl-Co. A oxidized by the citric acid cycle, the energy gain consists of three molecules of NADH, one FADH 2, and one nucleoside triphosphate (either ATP or GTP).

n In eight sequential reactions, including two decarboxylations, the citric acid cycle converts citrate to oxaloacetate and releases two CO 2. n The net reaction for the TCA is as follows： CH 3 COSCo. A+3 NAD++FAD+ADP/GDP+Pi+2 H 2 O → 2 CO 2+3 NADH+3 H++FADH 2+ATP/GTP+Co. ASH

Regulation of the TCA Cycle n n 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 n As intermediates of the citric acid cycle are removed to serve as biosynthetic precursors, they are replenished by anaplerotic reactions