Metabolism

Metabolism involves

• Catabolic reactions that break down large,

complex molecules to provide energy and
smaller molecules.

• Anabolic reactions that use ATP energy to

build larger molecules.

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Metabolism and Cell Structure
ATP and Energy

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 Stages of Metabolism
Catabolic reactions are organized as
Stage 1: Digestion and hydrolysis break
down large molecules to smaller
ones that enter the bloodstream.
Stage 2: Degradation breaks down molecules
to two- and three-carbon compounds.
Stage 3: Oxidation of small molecules in the
citric acid cycle and electron transport
provide ATP energy.
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 Stages of Metabolism
Catabolic reactions:
Stage 1: Digestion and
hydrolysis
break down large
molecules to smaller
ones that enter the
bloodstream.

Stage 2: Degradation
Further breaking and
some oxidation of
molecules to 2 & 3-
carbon compounds.

Stage 3: Oxidation
of small molecules to
CO2 & H2O in the citric
acid cycle and electron
transport provides
energy for ATP 5
synthesis.
CARBOHYDRATE
CARBOHYDRATE
METABOLISM
METABOLISM
Carbohydrate metabolism includes

1. Digestion of carbohydrates.
2. Absorption of digested carbohydrates.
3. Utilization of carbohydrates
 Utilization
A-Anabolic pathways:
Transforming small molecules into big molecules
constituting the body structures and machinery. It is
energy requiring, e.g., glycogenesis and lactose synthesis

B-Catabolic pathways:
Breakdown of large molecules into smaller molecules
to produce energy or smaller molecules or reducing
equivalents, e.g., HMP-shunt and uronic acid pathway.

C-Amphibolic pathways:
They are utilized for both anabolic and catabolic
purposes, e.g., glycolysis and Krebs' cycle.
 Fate of glucose
A-Oxidative fate:
•Major pathways: A. Glycolysis. B. Krebs' cycle.
•Minor pathways: A. Pentose shunt. B. Uronic acid
pathway.

B- Anabolic fates:
•Glycogenesis/glycogenolysis.
•Gluconeogenesis.
•Monosaccharides synthesis.
•Lactose synthesis.
•Glycolipids, glycoproteins and Proteoglycans
synthesis.
 Major Oxidative Pathways of
Glucose:

Glycolysis
Embden-Myerhof Parnas
(EMP)Pathway
Anaerobic Oxidation of Glucose
 Definition:

• It is a cascade of reactions that converts

glucose into two pyruvate molecules or into
lactate aiming at production of ATP and other
intermediates.
• It is also utilized in its opposite direction in
gluconeogenesis.

[glycolysis: from the Greek

glyk-, sweet, and lysis, splitting]
 Intracellular site and tissue
distribution:
It occurs in the cell cytosol of all tissues of the body.

1.RBCs:
are devoid of mitochondria and depend on glycolysis as the main source
of energy. Mammalian erythrocyte is unique in that about 90% of its
total energy requirement is provided by glycolysis.

2.Contracting muscles
due to occlusion of blood vessels by the muscular contraction that
decreases oxygen

3-Cornea, lens and some parts of retina

which have a limited blood supply and lack mitochondria which if
present would absorb and scatter light interfering with transparency.
4-Kidney (medulla), testicles, leukocytes and white
muscle fibers,
where there are relatively few mitochondria.

5-Cancer cells
due to dissociation of the high rate of glycolysis from
Krebs', i.e., anerobic production of lactate.

6-Brain and gastrointestinal tract also normally derive

most of their energy from glycolysis.
 Biological importance (or
Functions) of glycolysis:
1. Glucose oxidation producing ATP.
2. It is the major source of energy in certain tissues,
e.g., RBCs and skeletal muscles.
3. It provides pyruvic acid needed for Krebs' cycle.
4. It is a link with fat metabolism, e.g.,
dihydroxyacetone phosphate into glycerol 3-
phosphate in adipose tissue.
5. It a link with amino acid metabolism, e.g., 3-
phopshoglycerate into serine and pyruvate into
alanine and vice versa.
6. Production of 2,3-DPG that is important in tissue
oxygenation.
7. It is the major source of lactic acid that is
gluconeogenic.
8. Reversal of glycolysis is gluconeogenesis, an
important source of glucose.
9. Main pathway of metabolism of fructose from the
diet.
10. A small number of genetic diseases occur due to
deficiency in activity of enzymes of glycolysis, are
manifested mainly as hemolytic anemias.
11. Cancer cells are glycolytic producing large amount
of lactate, favoring a relatively acidic local pH in
the tumor, a situation that was utilized to develop
therapy for cancer that could be locally activated
by this acidic pH.
Steps of glycolysis
The Rapoport-Luebering Pathway
Overview
 In RBCs, glycolysis is modified by the Rapoport-
Luebering shunt.

 It is a biochemical pathway in mature erythrocytes

involving the formation of 2,3-
bisphosphoglycerate and which regulates oxygen
release from hemoglobin and delivery to tissues.
Hence, the name “ 2,3- bisphosphglycerate (2,3-
BPG) shunt.
The Pathway

There are 2 steps in this shunt:

1.Bisphosphoglycerate mutase
converts 1,3-BPG in to 2,3-BPG.
2.2,3-BPG is hydrolysed to 3-
phosphoglycerate by 2,3-
bisphosphoglycerate phosphatase.
ATP Yield:
Mature RBCs contain no
mitochondria, thus they depend only
upon glycolysis for energy production
.2 ATP
Role of 2,3-BPG in haemoglobin
function
BPG acts as an allosteric regulator of 2,3 
hemoglobin that has the ability to decrease the
. ,affinity of O2 to hemoglobin
When a hemoglobin molecule is O2 deficient, 2,3 
BPG inserts itself between the two beta chains,
where it contains positively charged amino acids
that form salt bridges with the negatively
.charged phosphate groups of 2,3-BPG
The lower affinity for O2 means that the 
hemoglobin’s delivery of O2 to the tissues is
.enhanced when needed
Regulation (or Control) of
Glycolysis
A. Key regulatory enzymes:
are those enzymes that catalyze the
irreversible steps of glycolysis that
include three steps as follows,

1-Phosphofructokinase:
It is an allosteric enzyme stimulated by
high levels of fructose-6- phosphate,
fructose-2,6-diphosphate (in liver), ADP
and AMP, Pi, and ammonia.
It is inhibited allosterically by ATP, low pH
and citrate.
2-Hexokinase:
Accumulation of glucose-6-phosphate and
inhibition of phosphofructokinase results in
accumulation of fructose-6-phosphate and
glucose-6-phosphate that allosterically inhibit
hexokinase.
3-Pyruvate kinase: It is inhibited also by
excess ATP, fatty acids, and acetyl-CoA
and is stimulated by fructose-1,6-
diphosphate, ADP and AMP
It is regulated by cAMP-dependent
phosphorylation-dephosphorylation
mechanism
B. Hormonal regulation:
1. Insulin:
Stimulates synthesis of glucokinase,
phosphofructokinase and pyruvate
kinase, so it stimulates glycolysis.
It also induces glucose transporters to
provide cells with glucose for glycolysis.

2-Adrenaline and glucagon are

inhibitory by inhibiting pyruvate kinase.
Pathways for Pyruvate

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Pyruvate: Aerobic Conditions

Under aerobic conditions (oxygen present),

 Three-carbon pyruvate is decarboxylated.
 Two-carbon acetyl CoA and CO2 are produced.

O O pyruvate
|| || dehydrogenase
CH3—C—C—O- + HS—CoA + NAD+
pyruvate
O
||
CH3—C—S—CoA + CO2 + NADH
acetyl CoA
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Pyruvate: Anaerobic Conditions
Under anaerobic conditions (without oxygen),
 Pyruvate is reduced to lactate.
 NADH oxidizes to NAD+ allowing glycolysis to continue.

O O lactate
|| || dehydrogenase
CH3—C—C—O- + NADH + H+
pyruvate
OH O
| ||
CH3—CH—C—O- + NAD+
lactate
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Lactate in Muscles

During strenuous exercise,

 Oxygen in the muscles is depleted.
 Anaerobic conditions are produced.
 Lactate accumulates. OH
│
C6H12O6 + 2ADP + 2Pi 2CH3–CH–COO- + 2ATP
glucose lactate
 Muscles tire and become painful.
After exercise, a person breathes heavily to repay the
oxygen debt and reform pyruvate in the liver.
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KREBS CYCLE

Discovered by Hans Krebs

in 1937

He received the Nobel Prize

in physiology or medicine in
1953 for his discovery
 The Citric acid cycle

It is called the Krebs cycle or the tricarboxylic and is the

“hub” of the metabolic system. It accounts for the
majority of carbohydrate, fatty acid and amino acid
oxidation. It also accounts for a majority of the
generation of these compounds and others as well.
Amphibolic - acts both catabolically and anabolically
3NAD+ + FAD + GDP + Pi + acetyl-CoA
3NADH + FADH + GTP + CoA + 2CO2
The citric acid cycle enzymes are found
in the matrix of the mitochondria
Substrates have to flow across the outer and inner
parts of the mitochondria
Glycogenesis
Glycogenesis
 Stores glucose by converting glucose to glycogen.
 Operates when high levels of glucose-6-phosphate
are formed in the first reaction of glycolysis.
 Does not operate when energy stores (glycogen)
are full, which means that additional glucose is
converted to body fat.

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Diagram of Glycogenesis

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Glycogenolysis
In glycogenolysis
 Glycogen is broken
down to glucose.
 Glucose molecules
are removed one by
one from the end of
the glycogen chain
to yield glucose-1-
phosphate.

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Glycogenolysis
Glycogenolysis
 Is activated by glucagon (low blood glucose).
 Bonds glucose to phosphate to form glucose-1-
phosphate.
glycogen-glucose + Pi
glycogen + glucose-1-phosphate

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Isomerization of Glucose-1-
phosphate
 The glucose-1-phosphate isomerizes to glucose-
6-phosphate, which enters glycolysis for energy
production.

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Glucose-6-phosphate

Glucose-6-phosphate
 Is not utilized by brain and skeletal muscle because
they lack glucose-6-phosphatase.
 Hydrolyzes to glucose in the liver and kidney, where
glucose-6-phosphatase is available providing free
glucose for the brain and skeletal muscle.

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Chapter 22 Metabolic Pathways for
Carbohydrates
22.8
Gluconeogenesis: Glucose Synthesis

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58
 Utilization of Glucose
Glucose
 Is the primary
energy source for
the brain, skeletal
muscle, and red
blood cells.
 Deficiency can
impair the brain
and nervous
system.
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59
 Gluconeogenesis: Glucose Synthesis

Gluconeogenesis is
 The synthesis of glucose from carbon atoms of
noncarbohydrate compounds.
 Required when glycogen stores are depleted.

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 Gluconeogenesis: Glucose Synthesis

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Gluconeogenesis: Glucose Synthesis
In gluconeogenesis,
 Glucose is synthesized from noncarbohydrates such
as lactate, some amino acids, and glycerol after they
are converted to pyruvate or other intermediates.
 Seven reactions are the reverse of glycolysis and use
the same enzymes.
 Three reactions are not reversible.
Reaction 1 Hexokinase
Reaction 3 Phosphofructokinase
Reaction 10 Pyruvate kinase
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Gluconeogenesis: Pyruvate to
Phosphoenolpyruvate
 Pyruvate adds a carbon to form oxaloacetate by two
reactions that replace the reverse of reaction 10 of
glycolysis.
 Then a carbon is removed and a phosphate added to
form phosphoenolpyruvate.

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 Phosphoenolpyruvate to Fructose-
1,6-bisphosphate
 Phosphoenolpyruvate is converted to fructose-1,6-
bisphosphate using the same enzymes in glycolysis.

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 Glucose Formation
Glucose forms when
 A loss of a phosphate from fructose-1,6-bisphosphate
forms fructose-6-phosphate and Pi.
 A reversible reaction converts fructose-6-phosphate to
glucose-6-phosphate.
 A phosphate is removed from glucose-6-phosphate.

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Different
Substrates
• LACTATE
• ALANINE
• GLUCOGENIC AA
• GLYCEROL
• PROPIONYL COA

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Regulation of gluconeogenesis and
glycolysis:
 inactivation of the glycolytic enzymes and activation
of the enzymes of gluconeogenesis
1. Pyruvate ↔ PEP
Pyruvate kinase - inactivation by cAMP
(glucagon)
Phosphoenolpyruvate carboxykinase -
induced by glucagon, epinephrine, and
cortisol

2. Fructose 1,6-P ↔ Fructose 6-P

Phosphofructokinase - activated
by fructose 2,6-P
Fructose 1,6-bisphosphatase - inhibited
by fructose 2,6-P

3. Glucose 6-P ↔ Glucose

Glucokinase - high Km for glucose,
induced by insulin
Glucose 6-phosphatase - induced during
fasting
 Cori Cycle

The Cori cycle

 Is the flow of lactate and glucose between the muscles
and the liver.
 Occurs when anaerobic conditions occur in active
muscle and glycolysis produces lactate.
 Operates when lactate moves through the blood stream
to the liver, where it is oxidized back to pyruvate.
 Converts pyruvate to glucose, which is carried back to
the muscles.

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Pathways for Glucose

are derived from

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Regulation of Glycolysis and
Gluconeogenesis
Regulation occurs as
 High glucose levels and insulin promote glycolysis.
 Low glucose levels and glucagon promote
gluconeogenesis.

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Regulation of Glycolysis and
Gluconeogenesis
TABLE 22.2

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THANK YOU

CARBOHYDRATES = ENERGY!

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