Download Lecture 7 Citric acid cycle

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

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.


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 Fructose6Phosphate
+ H2O
+ Pi
Glucose 6-Phosphate to Glucose

Gluconeogenesis is energetically expensive, but
essential.
2. Regulation of Gluconeogenesis
Lecture 6
The pentose phosphate pathway
of glucose oxidation

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).

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

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
G 6-P+ 2NADP+ H2O
6-phosphogluconate
dehydrogenase
ribulose 5-phosphate + CO2 + 2NADPH + 2H
6 NADP+
6 G6P
6 NADPH+H+
→
6 NADP+
G6P
6 Ribulose 5-phosphate +6 CO2
+
6 NADPH+ 6 H
6H2O+6CO2
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?

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.
Hans Krebs, 1900–1981
Stage 1: oxidation of fatty
acids, glucose, and some
amino acids yields acetylCoA.
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.
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.
FIGURE 16–8 Structure of citrate synthase.
(2) Formation of Isocitrate via cis-aconitate
(3) Oxidation of Isocitrate to α- Ketoglutarate and CO2
(4) Oxidation of α-Ketoglutarate to Succinyl -CoA and CO2
(5) Conversion of Succinyl-CoA 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)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).

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