Cellular respiration (glycolysis, TCA and ETC)

NSB 211: DIGESTIVE SYSTEM NUTRITION
AND METABOLISM

TOPIC;

•CELLULAR RESPIRATION
Lecturer: Dr. G. Kattam Maiyoh
11/20/13

GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION
AND METABOLISM/2013

Learning Objectives
• Explain why cells need breakdown
biomolecules (E.G. glucose)
• Describe the basic steps in;
– Glycolysis,
– The TCA cycle,
– The electron transport chain (ETC)

• Summarize the energy yield of all above steps
cellular respiration
11/20/13

GKM/NSB 211: DIGESTIVE SYSTEM
NUTRITION AND METABOLISM/2013

Overview of Cellular Respiration

11/20/13


Overview of Cellular Respiration
• Cellular respiration is the step-wise release of
energy from carbohydrates and other
molecules; energy from these reactions is
used to synthesize ATP molecules.
• This is an aerobic process that requires oxygen
(O2) and gives off carbon dioxide (CO2), and
involves the complete breakdown of glucose
to carbon dioxide and water.

11/20/13


• Metabolism refers to all the chemical reactions
of the body
– some reactions produce the energy stored in
ATP that other reactions consume
– all biological molecules will eventually be
broken down and recycled or excreted from
the body

11/20/13


Catabolism and Anabolism
• 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
(adenosine triphosphate) molecule.
11/20/13


25-6

ATP Molecule & Energy
a

b
• Each cell has about 1 billion ATP molecules that last for less than
one minute
• Over half of the energy released from ATP is converted to heat
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25-7

Mechanisms of ATP Generation
• Phosphorylation is the addition of phospahate
group.
– bond attaching 3rd phosphate group contains stored
energy

• Mechanisms of phosphorylation
– within animals
• substrate-level phosphorylation in cytosol
• oxidative phosphorylation in mitochondria

– in chlorophyll-containing plants or bacteria
• photophosphorylation.
11/20/13

NUTRITION AND25-8
METABOLISM/2013

Phosphorylation in Animal Cells
• In cytoplasm (1)
• In mitochondria (2, 3 & 4)

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25-9

• (Insert Fig. 7.4a)

11/20/13


Sld 38

Carbohydrate Metabolism--In Review
• In GI tract
– polysaccharides broken down into simple sugars
– absorption of simple sugars (glucose, fructose &
galactose)

• In liver
– fructose & galactose transformed into glucose
– storage of glycogen (also in muscle)

• In body cells --functions of glucose
– oxidized to produce energy
– conversion into something else
– storage energy as triglyceride in fat
11/20/13

25-11

Glucose Movement into Cells
• In GI tract and kidney tubules,
Na+/glucose symporters
• Most other cells, GluT facilitated
diffusion transporters move
glucose into cells
• Glucose 6-phosphate forms
immediately inside cell (requires
ATP) thus, glucose hidden in cell
• Concentration gradient favorable
for more glucose to enter

11/20/13


25-12

Glucose Catabolism
• Cellular respiration
– 4 steps are involved
– glucose + O2 produces
H2O + energy + CO2

• Anaerobic respiration
– called glycolysis (1)
– Results in formation of acetyl CoA (2)
is transitional step to Krebs cycle

• Aerobic respiration
– Krebs cycle (3) and electron transport chain (4)
11/20/13

GKM/NSB 211: DIGESTIVE SYSTE
M NUTRITION AND METABOLISM/2013

25-13

• Each step of cellular respiration
requires a separate enzyme.
• Some enzymes use the oxidationreduction coenzyme NAD+
(nicotinamide adenine
dinucleotide).
• When a metabolite is oxidized,
NAD+ accepts two electrons plus a
hydrogen ion (H+) and NADH
results; NAD+ can also reduce a
metabolite by giving up
electrons.
• FAD (flavin adenine dinucleotide)
is sometimes used instead of
NAD+.
11/20/13


6 CH OPO 2−
2
3
5
O

H
4

OH

H
OH
3

H

H
2

H
1

OH

OH

glucose-6-phosphate

Glycolysis takes place in the cytosol of cells.
Glucose enters the Glycolysis pathway by conversion
to glucose-6-phosphate.
Initially there is energy input corresponding to
cleavage of two ~P bonds of ATP.
11/20/13


6 CH2OH
5

H
4

OH

O

H
OH

H
2

3

H

OH

glucose

6 CH OPO 2−
2
3
5
O

ATP ADP
H
H
1

OH

Mg2+

4

H
OH

OH

3

H
1

H
2

OH

Hexokinase H
OH
glucose-6-phosphate

1. Hexokinase catalyzes:
Glucose + ATP  glucose-6-P + ADP
The reaction involves nucleophilic attack of the C6
hydroxyl O of glucose on P of the terminal phosphate
of ATP.
ATP binds to the enzyme as a complex with Mg++.

Glycolysis & Fate of Pyruvic Acid
• Breakdown of six-carbon
glucose molecule into 2 threecarbon molecules of pyruvic
acid
– 10 step process occurring in
cell cytosol
– produces 4 molecules of
ATP after input of 2 ATP
– utilizes 2 NAD+ molecules
as hydrogen acceptors
11/20/13


25-17

10 Steps of Glycolysis

11/20/13
GKM/CHE 214/LEC 03/SEM 02/2011

25-18

11/20/13


If O2 shortage in a cell
•Pyruvic acid is reduced to lactic acid so that
NAD+ will be still available for further
glycolysis
•This process is known as fermentation
•Lactic acid rapidly diffuses out of cell to
blood
•Liver cells remove it from blood & convert it
back to pyruvic acid
11/20/13


Why does fermentation occur?
Pyruvate is reduced to lactate when
oxygen is not available because
fermentation uses NADH and
regenerates NAD+.
In this way NAD+ is now free to pick up
more electrons during early steps of
glycolysis; this keeps glycolysis going.
11/20/13


Two types of Anaerobic Respiration

Fermentation-yeast

Lactic Acid or lactate-muscles
11/20/13


Advantages and Disadvantages of
Fermentation
• Fermentation can provide a rapid burst of ATP
in muscle cells, even when oxygen is in limited
supply.
• Lactate, however, is toxic to cells.
• Initially, blood carries away lactate as it forms;
eventually lactate builds up, lowering cell pH,
and causing muscles to fatigue.
• Oxygen debt occurs, and the liver must
reconvert lactate to pyruvate.
11/20/13


Efficiency of Fermentation
• Two ATP produced during fermentation are
equivalent to 14.6 kcal; complete oxidation of
glucose to CO2 and H2O represents a yield of
686 kcal per molecule of glucose.
• Thus, fermentation is only 2.1% efficient
compared to cellular respiration.
• (14.6/686) x 100 = 2.1%

11/20/13


Glycolysis summary
•Inputs:
•Glucose
•2 NAD+
•2 ATP
•4 ADP + 2 P

11/20/13

•Outputs:
•2 pyruvate
•2 NADH
•2 ADP
•2 ATP (net gain)


Transition Reaction
• The transition reaction connects glycolysis to
the citric acid cycle, and is thus the transition
between these two pathways.
• Pyruvate is converted to a C2 acetyl group
attached to coenzyme A (CoA), and CO2 is
released.
• During this oxidation reaction, NAD+ is
converted to NADH + H+; the transition
reaction occurs twice per glucose molecule.
11/20/13


Formation of Acetyl Coenzyme A
• Pyruvic acid enters the
mitochondria with help of
transporter protein
• Decarboxylation
– pyruvate dehydrogenase converts 3
carbon pyruvic acid to 2 carbon
fragment (CO2 produced)
– pyruvic acid is oxidized so that NAD+
becomes NADH

• 2 carbon fragment (acetyl group) is
attached to Coenzyme A to form
Acetyl coenzyme A which enter
Krebs cycle
– coenzyme A is derived from
pantothenic acid (B vitamin).
11/20/13


25-27

Krebs Cycle (Citric Acid Cycle)
• Citric acid cycle – a cyclical oxidationreduction & decarboxylation reactions
occurring in matrix of mitochondria
• Gives off CO2 and produce one ATP per cycle;
occurs twice per glucose molecule
• It finishes the same as it starts (4C)
– acetyl CoA (2C) enters at top & combines with a
4C compound
– 2 decarboxylation reactions peel 2 carbons off
again when CO2 is formed

THE TCA

The names of the various enzymes in
the previous slide are indicated in the
figure below


What happens in the cycle?
• During the cycle, oxidation occurs when NAD+
accepts electrons in three sites and FAD
accepts electrons once.
• A gain of one ATP per every turn of the cycle;
it turns twice per glucose.
• During the citric acid cycle, the six carbon
atoms in glucose become CO2.
• The transition reaction produces two CO2, and
the citric acid cycle produces four CO2 per
molecule of glucose.
11/20/13


Products of the Krebs Cycle
• Energy stored in bonds is released step by step to form several
reduced coenzymes (NADH & FADH2) that store the energy
• In summary: each Acetyl CoA
molecule that enters the Krebs
cycle produces yields;
– 2 molecules of CO2
• one reason O2 is needed
– 3 molecules of NADH + H+
– one molecule of ATP
– one molecule of FADH2
• Remember, each glucose
produced 2 acetyl CoA molecules
11/20/13


Citric acid cycle inputs and outputs per
glucose molecule
•Inputs:
•2 acetyl groups
•6 NAD+
•2 FAD
•2 ADP + 2 P

•Outputs:

½ of the above per cycle
11/20/13


•4 CO2
•6 NADH
•2 FADH2
•2 ATP

The Electron Transport Chain
• Involves a series of integral
membrane proteins in the
inner mitochondrial
membrane capable of
oxidation/reduction
• Each electron carrier is
reduced as it picks up
electrons and is oxidized as it
gives up electrons
• Small amounts of energy is
released in small steps
• Energy used to form ATP by
chemiosmosis

Chemiosmosis

• Small amounts of energy
released as substances are
passed along inner
membrane
• Energy used to pump H+ ions
from matrix into space
between inner & outer
membrane
• High concentration of H+ is
maintained outside of inner
membrane
• ATP synthesis occurs as H+
diffuses through a special H+
channel in inner membrane


Steps in Electron Transport

• Carriers of electron transport chain are clustered into 3 complexes
that each act as proton pump (expel H+)
• Mobile shuttles pass electrons between complexes
• Last complex passes its electrons (2H+) to a half of O2 molecule to
form a water molecule (H2O)

Proton Motive Force & Chemiosmosis

•
•

Buildup of H+ outside the inner membrane creates + charge
– electrochemical gradient potential energy is called proton motive force
ATP synthase enzyme within H+ channel uses proton motive force to synthesize
ATP from ADP and P

Energy yields from Glycolysis -TCA
• Glycolysis and the citric acid cycle accounts for
four ATP.
• ETC accounts for 32 or 34 ATP, and the grand
total of ATP is therefore 36 or 38 ATP.
• Cells differ as to the delivery of the electrons
from NADH generated outside the
mitochondria.
• If they are delivered by a shuttle mechanism to
the start of the electron transport system, 6 ATP
result; otherwise, 4 ATP result.

• Most ATP is produced by the electron
transport system and chemiosmosis.
• Per glucose molecule, ten NADH and two
FADH2 take electrons to the electron transport
system; three ATP are formed per NADH and
two ATP per FADH2.
• Electrons carried by NADH produced during
glycolysis are shuttled to the electron
transport chain by an organic molecule.
7-39

A Summary of the Energy Yield of
Aerobic Metabolism

Figure 25.7

Thank you for listening !!

11/20/13


Cellular respiration (glycolysis, TCA and ETC)

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