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METABOLISM OF CARBOHYDRATE

Harliansyah, PhD

Department of
Biochemistry
Faculty of Medicine
University of YARSI
Jakarta,
Tibtech. 28(1). 2008
Metabolism
• Metabolism is all the biochemical reactions by which food is
transformed into energy store (ATP) and by which our bodies
require to function, including anabolism and catabolism.
• Catabolic reactions breakdown complex organic compounds:
- providing energy (exergonic)
- Glycolysis, Krebs cycle and Electron transport
• Anabolic reactions synthesize complex molecules from small
molecules:
- requiring energy (endergonic)
• Exchange of energy requires use of ATP molecule.
Integration of metabolism is essential on both
short-term and long-term bases

Short-term : maintenance of a stable blood glucose level ( 2.5-3


mmol/s for brain function)

Blood sugar, Glucose is not an “inert and gentle”


component of our diet.
Glucose is Toxic !

Long-term : High blood levels of glucose lead to protein


denaturation and the development
of blindness, neuropathy and the kidney damage seen
in diabetes.
General Features of Metabolism
• Occurs in specific cellular (tissue and organ) locations as a
series of enzyme-catalyzed linear, branched or circular
reactions, or pathways.
• Highly coupled and interconnected (“Every road leads to
Rome”).
• Highly regulated (often reciprocally) to achieve the best
economy (“Balanced supply and demand”).
• The number of reactions is large (over 1000), however, the
number of types of reactions is relatively small (what
happens in animal respiration happens in plant
photosynthesis).
• Well conserved during evolution: reflecting the unity of the
life phenomena (“what happens in bacteria happens in
human being”).
How Cells Harvest Chemical Energy

Introduction to Cell Metabolism

Glycolysis

Aerobic Cell Respiration

Anaerobic Cell Respiration


Breathing and Cell Respiration are related

O2 CO2 BREATHING

Lungs

Muscle cells
CO2 Bloodstream O carrying out
2

CELLULAR
RESPIRATION
Sugar + O2  ATP + CO2 + H2O
Cellular Respiration uses oxygen and glucose to produce
Carbon dioxide, water, and ATP.

Glucose Oxygen gas Carbon Water Energy


dioxide
How efficient is cell respiration?

Energy released Energy released Gasoline energy


from glucose from glucose converted to
(as heat and light) banked in ATP movement
100%

About
40% 25%
Burning glucose “Burning” glucose Burning gasoline
in an experiment in cellular respiration in an auto engine
Reduction and Oxidation

OILRIG

Oxidation is losing electrons

Reduction is gaining electrons

Loss of hydrogen atoms

Energy
Glucose
Gain of hydrogen atoms

Glucose gives off energy as is is oxidized


Reduction and Oxidation
OILRIG
Gain or loss of electrons is often in the form of hydrogen.
The hydrogen is then passed to a coenzyme such as NAD+
Reduction and Oxidation

What are some common co-enzymes?


NAD+ and FAD
NAD+ + 2 H  NADH + H+

FAD + 2H  FADH2

Remember that H = 2 electrons and 2H+


Reduction and Oxidation

These co-enzymes are very important for cell


respiration because they transfer high-energy
electrons to electron transport systems (ETS).
Reduction and Oxidation

As the electrons move from carrier to carrier,


energy is released in small quantities.

Electron transport system


(ETS)
Generation of ATP

There are two ways to generate ATP


Chemiosmosis

Substrate-Level Phosphorylation
Generation of ATP

Chemiosmosis

Cells use the energy


released by “falling”
electrons in the ETS to
pump H+ ions across a
membrane

Uses the enzyme ATP


synthase.
Generation of ATP

Chemiosmosis
Generation of ATP

Substrate Level Phosphorylation

Enzyme

ATP can also be


Adenosine
made by transferring
phosphate groups
from organic substrate
molecules to ADP
Adenosine

product
Figure 6.7B
Generation of ATP

Substrate Level Phosphorylation

Enzyme

ATP can also be


Adenosine
made by transferring
phosphate groups
from organic substrate
molecules to ADP
Adenosine

product
Figure 6.7B
Classification of organisms based on
trophic (“feed”) strategies

• Autotrophs—synthesize all cellular


components from simple inorganic
molecules (e.g, H2O, CO2, NH3, H2S).
• Heterotrophs—Derive energy from
oxidation of organic compounds (made
by autotrophs).
Metabolism allows the cycling of C/O
and the flow of energy in the biosphere

glucose

Producers Consumer

H2O
Metabolism also
allows the cycling
of N in the biosphere

(NH4+)

NO3-
NO2-
(Fuels)

Exergonic Oxidation

Biodegradation
Output of energy

Complex Simpler
Metabolites Metabolites

Input of energy
Endergonic Reduction

Biosynthesis
(Fuels) The role of Metabolism

Extract energy and reducing power

ATP: Energy currency


Also for mobility,
transport of nutrients
and so on.

Generate all biomolecules


Coenzymes (vitamines)

Amino acids
carbohydrate hormones

nucleotid

Amino ac

lipids

22nd edition designed by Dr. Donald E. Nicholson


General Outline

Glucose

Glycolysis

Oxygen No Oxygen
Pyruvic Acid
Aerobic Anaerobic

Transition Reaction Fermentation


Krebs Cycle
ETS

36 ATP
Glycolysis

Where? The cytosol

What? Breaks down glucose to pyruvic acid


Anabolism
Catabolism
GLYCOLYSIS
• The specific pathway by which the body gets
energy from monosaccharides
First stage is ACTIVATION
• At the expense of 2ATPs glucose is
phosphorylated
Step #1
formation of glucose-6-phosphate
Step # 2
isomerization to fructose-6-phosphate
Step # 3
Second phosphate group is attached to yield fructose-1,6-bisphosphate

Second stage is C6 to 2 molecules of C3


Step # 4
Fructose-1,6-bisphosphate is broken down into two C3 fragments
glyceraldehyde-3-phosphate (G-3-P) and dihydroxyacetone phosphate
(DHAP)

Only G-3-P is oxidized in glycolysis. DHAP is converted to G-3-P as the


latter diminishes.
ATP-YIELDING Third stage
Step # 5
Glyceraldehyde-3-phosphate is oxidized to 1,3-bisphosphoglycerate; hydrogen of
aldehyde is removed by NAD+

Step # 6
Phosphate from the carboxyl group is transferred to the ADP yielding ATP and 3-
phosphoglycerate

Step # 7
Isomerization of 3-phosphoglycerate to 2-phosphoglycerate
Step # 8
Dehydration of 2-phosphoglycerate to phosphoenolpyruvate (PEP)

Step # 9
Removal of the remaining phosphate to yield ATP and pyruvate

Step # 10
Reductive decarboxylation of pyruvate to produce ethanol and CO2
REACTIONS OF GLYCOLYSIS
STEP REACTION ENZYME REACTION ΔG in
TYPE kJ/mol

1 Glucose + ATP  Hexokinase Phosphoryl -33.5


transfer
G-6-P + ADP + H+

2 G-6-P  F-6-P Phosphoglucose Isomerization -2.5


isomerase

3 F-6-P + ATP  Phosphofructo- Phosphoryl -22.2


kinase transfer
F-1,6-BP + ADP + H+
STEP REACTION ENZYME REACTION TYPE ΔG in
kJ/
mol
4 F-1,6-BP  DHAP + GAP Aldolase Aldol cleavage -1.3

5 DHAP  GAP Triose Isomerization +2.5


phosphate
isomerase
6 GAP + Pi + NAD+  Glyceraldehyde Phosphorylation +2.5
1,3-BPG + NADH + H+ -3-Phosphate coupled to
Dehydrogenase oxidation
7 1,3-BPG + ADP  Phosphoglycer- Phosphoryl +1.3
3-phosphoglycerate +ATP ate kinase transfer

8 3-phosphoglycerate  Phosphoglyce- Phosphoryl shift +0.8


2-phosphoglycerate rate mutase

9 2-phosphoglycerate  Enolase Dehydration -3.3


PEP + HOH

10 PEP + ADP + H+  pyruvate + ATP Pyruvate kinase Phosphoryl -16.7


transfer
Steps 1 – 3 A fuel Glucose
molecule is energized, Step
using ATP. 1
Glycolysis Glucose-6-phosphate
2

Fructose-6-phosphate
3
Energy In: 2 ATP
Fructose-1,6-diphosphate
Step 4 A six-carbon 4
intermediate splits into
two three-carbon Glyceraldehyde-3-phosphate
intermediates. (G3P)

5
Step 5 A redox
reaction generates
NADH. 1,3-Diphosphoglyceric acid
(2 molecules)
6

Steps 6 – 9 ATP 3-Phosphoglyceric acid


Energy Out: 4 ATP and pyruvic acid
are produced.
7 (2 molecules)

2-Phosphoglyceric acid
8 (2 molecules)

2-Phosphoglyceric acid
(2 molecules)

NET 2 ATP 9
Pyruvic acid
(2 molecules
per glucose molecule)
Maintenance of glucose homeostasis

Body cells
Insulin take up more
Beta cells of glucose.
pancreas are stimulated
to release insulin
into the blood.
Liver takes
up glucose
and stores it
as glycogen.
STIMULUS:
Blood glucose level
Rising blood glucose
declines to set point;
level (for instance, after
stimulus for insulin
eating a carbohydrate-
release diminishes.
rich meal)

Homeostasis:
Blood glucose level
(about 90 mg/100 mL)

Blood glucose level STIMULUS:


rises to set point; Dropping blood glucose
stimulus for glucagon level (for instance, after
release diminishes. skipping a meal)

Alpha cells of pancreas


are stimulated to release
Liver breaks glucagon into the blood.
down glycogen
and releases
glucose into Glucagon
blood.
General Outline

Glucose

Glycolysis

Oxygen No Oxygen
Pyruvic Acid
Aerobic Anaerobic

Transition Reaction Fermentation


Krebs Cycle
ETS

36 ATP
General Outline of Aerobic Respiration

Glycolysis

Transition Reaction

Krebs Cycle

Electron Transport System


Transition Reaction

Each pyruvic acid molecule is broken down to form


CO2 and a two-carbon acetyl group, which enters the
Krebs cycle

Pyruvic Acid Acetyl CoA


General Outline of Aerobic Respiration

Glycolysis

Transition Reaction

Krebs Cycle

Electron Transport System


Krebs Cycle

Where? In the Mitochondria

What? Uses Acetyl Co-A to generate ATP, NADH,


FADH2, and CO2.
Krebs Cycle
General Outline of Aerobic Respiration

Glycolysis

Krebs Cycle

Electron Transport System


Electron Transport System

Protein
complex
Intermembrane
Electron
space
carrier

Inner
mitochondrial
membrane
Electron
flow
Mitochondrial
matrix

ELECTRON TRANSPORT CHAIN ATP


Figure 6.12 SYNTHASE
Electron Transport System
Electron Transport System

For each glucose molecule that enters cellular


respiration, chemiosmosis produces up to 38 ATP
molecules
Overview of Aerobic Respiration
General Outline

Glucose

Glycolysis

Oxygen No Oxygen
Pyruvic Acid
Aerobic Anaerobic

Transition Reaction Fermentation


Krebs Cycle
ETS

36 ATP
Fermentation
Requires NADH generated by glycolysis.

Where do you suppose these reactions take place?

Yeast produce carbon dioxide and ethanol

Muscle cells produce lactic acid

Only a few ATP are produced per glucose


Fermentation
Thanks for you
attention