Glycolysis and TCA Cycle

OUTLINE CHAPTER
Introduction:
 Glycolysis
 TCA cycle
 conclusion
GLYCOLYSIS
CONTENTS
1. Introduction
2. Site of reaction
3. Steps of glycolysis
4. Reversible and irreversible reaction
5. Energetics of glycolysis
6. Regulation
INTRODUCTION
 Glycolysis from Greek words (glyco –sweet suger, lysis–
dissolution) .
 It is universal pathway in the living cells
 This pathway is referred as Embden-Meyerhof pathway
(E.M pathway) and discovered in 1940
o Glycolysis is defined as the sequence of the reaction

converting glucose (or glycogen) to pyruvate or lactate
with production of ATP
SALIENT FEATURES
a. Glycolysis takes place in all cells of the body , the enzyme of
this pathway are present in the cytosomal fraction of the cell
b. Glycolysis occur in the absence of oxygen known as
anaerobic condition , or in the presence of oxygen that
known as Aerobic condition
c. Gycolysis is a major pathway for ATP synthesis in the tissues
lacking mitochondria e.g erythrocyte ,cornea ,lens ,etc
d. Gycolysis is very essential for brain which is dependent on
glucose for energy
e. Gycolysis is central metabolic pathway which many of its
intermediates providing branch point to other pathways and
useful for amino acids and fats
SITE :
 Intracellular
location: Cytosol
 Organ location: all tissue cells, but it is of
physiological importance in :
a. Tissue with no mitochondria : e.g mature
RBCs
b. Tissues undergo frequent oxygen lack : skeletal
muscles especially during exercise
STEPS OF GLYCOLYSIS
1. Phosphorylation of Glucose
2. Conversion of Glucose 6-phosphate to Fructose 6-Phosphate
3. Phosphorylation of Fructose 6-phosphate to Fructose 1,6-
Bisphosphate
4. Cleavage of Fructose 1,6-Bisphosphate
5. Interconversion of the Triose Phosphates
6. Oxidation of Glyceraldehyde 3-Phosphate to l,3-
Bisphosphoglycerate
7. Phosphoryl Transfer from l,3-Bisphosphoglycerate to ADP
8. Conversion of 3-Phosphoglycerate to 2- Phosphoglycerate
9. Dehydration of 2-Phosphoglycerate to phospho-enol pyruvate
10. Transfer of the Phosphoryl Group from phosphoenol pyruvate
to ADP
REVERSIBLE AND IRREVERSIBLE REACTION
 Most of the reactions of glycolysis are reversible

However,the three steps catalysed by the
enzymes hexokinase (or glucokinase),
phosphofructokinase and pyruvate kinase, are
irreversible.
These three stages mainly regulate glycolysis.
 The reversal of glycolysis, with alternate
arrangements made at the three irreversible
stages, leads to the synthesis of glucose from
pyruvate (gluconeogenesis)
ENERGETICS OF GLYCOLYSIS
A. the 2 molecules of glyceraldehyde-3 phosphate

are converted into 2 pyruvate molecules known
as Aerobic glycolysis.
B. The 2 molecules of glyceraldehyde-3phosphate
also converted to 2 lactate molecules known as
anaerobic glycolysis
C. These steps produce ATP molecules ( energy
production)
 Net production of aerobic glycolysis – 10-2 = 8 ATP
 Net production anaerobic glycolysis – 4-2 = 2 ATP
REGULATION
A. Enzymes regulation:
 The rate of glycolysis is regulated by controlling of the three
irreversible enzymes ( key enzymes)
 These enzymes catalyze what is committed reaction of the
pathway
 These enzymes are the following:
a. Hexokinase/ Glucokinase
b. Phosphofructokinase
c. Pyruvate Kinase
B. Hormonal regulation:
d. insulin stimulates synthesis of all key enzymes of glycolysis. It
is secreted after meal ( in response to high blood glucose level).
e. Glucagon inhibits the activity of all key enzymes of glycolysis.
It is secreted in response to low blood glucose level.
DIFFERENCE B/WEEN AEROBIC &
ANAEROBIC
Aerobic Anaerobic
1. End product Pyruvate Lactate
2. Energy 6 or 8 ATP 2 ATP
3. Regeneration of NAD+ Through respiratory Through lactate

chain in Mitochondria
4. Availability to TCA in Available and 2 pyruvate Not available as lactate is

Mitochondria can be oxidized to give a cytosolic substrate
30 ATP
TCA CYCLE
CONTENTS
1. Introduction
2. Site of reaction
3. Steps of TCA Cycle
4. Energetics
5. Regulation
MITOCHONDRIAL PATHWAY FOR GLUCOSE
OXIDATION
 Complete oxidation of glucose occurs in both

cytosol ( glycolysis) and mitochondrial ( Kreb’s
cycle).
 In the presence of O2 , pyruvate ( the end product)
of glycolysis) passes by special pyruvate transporter
into mitochondria which proceeds as follows:
a. Oxidation decarboxylation of pyruvate to acetyl CoA
b. Acetyl CoA is then oxidized completely to CO2, H2O
through kreb’s cycle.
INTRODUCTION
 The citric acid cycle ( kreb’s cycle) or tricarboxylic
acid (TCA) is the important metabolic pathway for
energy supply to the body.
 60-70% of the ATP is synthesized in kreb’s cycle
 Citric acid cycle is essential because its involves the

oxidation of Acety-CoA to CO2 and H2O.
 It is the most important central pathway connecting
almost all the individual metabolic pathways
 The cycle was proposed by Hans Adolf kreb’s in
1937, the based on the studies of oxygen consumption
on pigeon breast muscle
SITE OF REACTION
 The enzymes of TCA cycle are located in mitochondria

Steps of reaction
 1.Formation of citrate : kreb’s cycle starts with the
condensation of acetyl coA and oxaloacetate, catalysed by the
enzyme citrate synthase
 2and 3.Citrate is isomerized to isocitrate by enzyme aconitase,
this achieved in two stage reaction of dehyration and also by
rehydration through the formation of intermediate cis-aconitate
 4. and 5. Formation of a-ketoglutarate :The enzyme isocitrate
dehydrogenase (lCD)catalyses the conversion (oxidative
decarboxylation) of isocitrate to oxalosuccinate and then to α-
ketoglutarate.The formation of NADH and the liberation of
CO2 occur at this stage.
 6.Conversion of α-ketoglutarate to succinyl CoA occurs
through oxidative decarboxylation, catalysed by α-
ketoglutarate dehydrogenase complex. This enzyme is
dependent on five cofactors-TPP, lipoamide, NAD+, FAD and
CoA.
 7-Formation of succinate : Succinyl CoA is converted to
succinate by succinate thiokinase. This reaction is coupled
with the phosphorylation of GDP to GTP. This is a substrate
level phosphorylation. GTP is converted to ATP by the enzyme
nucleoside diphosphate kinase.
 8-Conversion of succinate to fumarate :Succinate is oxidized
by succinate dehydrogenase to fumarate. This reaction results
in the production of FADH2 and not NADH
 9-Formation of malate : The enzyme fumarase catalyses the
conversion of fumarate to malate with the addition of H2O
 10- Conversion of malate to oxaloacetate :Malate is then
oxidized to oxaloacetate by malate dehydrogenase. The third
and final synthesis of NADH occurs at this stage. The
oxaloacetate is regenerated which can combine with another
molecule of acetyl CoA, and continue the cycle.
ENERGETICS OF TCA CYCLE
 During the process of oxidation Acety coA via citric acid

cycle 4 reducing equivalents
(3 NADH and one FADH2 ) are produced.
 Besides there is one substrate level phosphorylation
(GTP) , thus a total twelve ATP are produced from one
Acetyl CoA.
 Glucose oxidation : 38 ATP
 Pyruvate oxidation : 15 ATP
 Acetyl CoA : 12 ATP

CITRIC ACID CYCLE
CITRIC ACID CYCLE
AMPHIBOLIC NATURE OF THE
CITRIC ACID CYCLE
 The citric acid cycle provides various intermediates
for the synthesis of many compounds needed by the
body. Krebs cycle is both catabolic and anabolic in
nature, hence regarded as amphibolic
 TCA cycle is actively involved in gluconeogenesis,
Transamination and deamination The most
important synthetic ( anabolic)reactions connected
with TCA cycle
FUNCTION ( SIGNIFICANCE) OF TCA
 TCA cycle is amphibolic i.e has catabolic ( breakdown)
and anabolic (formation) functions:
 Catabolic functions: TCA is the final common pathway
for oxidation of carbohydrates , fats, and proteins (amino
acids).
 Anabolic functions: formation of :
a. Amino acids : e.g α-ketoglutarate---transmination--=

Glutamate.
b. Glucose : e.g α-ketoglutarate----Gluconeogenesis-=
Glucose.
c. Fatty acid and cholesterol: from acetyl CoA
SUMMARY OF TCA CYCLE
 The citric acid cycle is the final pathway for the oxidation of
carbohydrate, lipid and protein. Their common end metabolite,
acetyl CoA , reacts with oxaloacetete to form citrate.
 By series of dehyrogenations and decarboxylations citrate is
degraded ,reducing coenzymes ,releasing 2Co2 and
regenerating oxaloacetate.
 The cycle is the major pathway for the formation of ATP and
located in the matrix of mitochondria adjacent to the enzymes
of the respiratory chain and oxidative phosphorylation
 Citric acid cycle is amphibolic, since in addition to oxidation it
is important in the provision of carbon skeletons for
gluconegenesis , fatty acid synthesis and interconversion of
amino acids
CITRIC ACID CYCLE SUMMARY

Glycolysis and TCA Cycle

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What are the main steps of glycolysis?

What are the main steps of glycolysis?

What are some of the salient features of glycolysis?

What are some of the salient features of glycolysis?

OUTLINE CHAPTER

 This pathway is referred as Embden-Meyerhof pathway

(E.M pathway) and discovered in 1940

o Glycolysis is defined as the sequence of the reaction

 Most of the reactions of glycolysis are reversible

A. the 2 molecules of glyceraldehyde-3 phosphate

1. End product Pyruvate Lactate

2. Energy 6 or 8 ATP 2 ATP

3. Regeneration of NAD+ Through respiratory Through lactate

4. Availability to TCA in Available and 2 pyruvate Not available as lactate is

 Complete oxidation of glucose occurs in both

 Citric acid cycle is essential because its involves the

 The enzymes of TCA cycle are located in mitochondria

 During the process of oxidation Acety coA via citric acid

 Pyruvate oxidation : 15 ATP

 Acetyl CoA : 12 ATP

a. Amino acids : e.g α-ketoglutarate---transmination--=

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