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2023
METABOLISM

•TriCarboxylic Acid (TCA) cycle

•Electron transport chain (ETC)
•Oxidative phosphorylation

Dr. Geoffrey K. Maiyoh

Biochemistry and Clinical Chemistry

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1. Cellular respiration
• A set of metabolic reactions and processes that take place in
the cells of organisms to generate biochemical energy from
nutrients and convert it into adenosine triphosphate (ATP),
and then release waste products.

ETC
OXPHOS
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•CO2 and H2O = WASTE
•HMP shunt is the alternative route of glucose breakdown
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2 (a) Oxidation

A reaction that involves the overall loss of electrons (e-) from a specific
molecule or atom.
• Can occur with the addition of an oxygen or
by the removal of a hydrogen.

(b) Reduction
• A reaction that results in the overall gain of
electrons to a specific molecule or atom.

• Can occur with the addition of a hydrogen

atom or by the removal of an oxygen atom.
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3. Redox reaction

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4. Adenisine Triphosphate (ATP)
• The molecule from which cells derive energy.
• Comprised of an adenisine molecule bonded to three phosphates.
• Each phosphate bond contains energy, especially the third bond.
• By breaking that one bond and reducing ATP to adenisine diphosphate
(ADP), the cell can get the energy to carry out its various processes.

• ATP is therefore the perfect energy currency for the cell

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Mechanisms of ATP Generation

• Phosphorylation of ADP is the addition of

phosphate group.
• bond attaching 3rd phosphate group contains
stored energy
• Mechanisms of phosphorylation within animals
• Substrate-level phosphorylation (glycolysis)
• Oxidative phosphorylation in mitochondria

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5. Mitochondria
• Organelles within the cell that are also
known as the powerhouses of the cell.
• Most of the ATP needed for daily
functioning is produced within its
bounds during;

I. The citric acid cycle,

II. The electron transport chain
III. Oxidative phosphorylation.

Mitochondria: takes in nutrients, breaks them down, and creates energy rich molecules for the cell.

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6. Catabolism and Anabolism
• Catabolic reactions breakdown complex organic
compounds providing energy (exergonic)
• Examples include: glycolysis, Krebs cycle,
electron transport and HMP shunt
• Anabolic reactions synthesize complex molecules
from small molecules requiring energy (endergonic)
•
• Exchange of energy requires use of ATP (adenosine
triphosphate) molecule.

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 ATP Molecule & Energy

• Each of our cells 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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Glycolysis overview
• Breakdown of six-carbon glucose
molecule into 2 three-carbon
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

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 The 10 Steps of Glycolysis

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Glycolysis summary
•Inputs: •Outputs:
•Glucose •2 pyruvate
•2 NAD+ •2 NADH
•2 ATP •2 ADP
•4 ADP + 2 P •2 ATP (net gain)

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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 2C 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.

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 Formation of Acetyl
Coenzyme A

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 The link between Glycolysis and the TCA
Cycle is ACETYL COA

PDH

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Regulation of formation of acetyl-
COA

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 Krebs Cycle (Citric Acid Cycle)
• Citric acid cycle – a series of cyclical oxidation-reduction &
decarboxylation reactions occurring in matrix of mitochondria
• Gives off CO2 and produces one ATP per cycle; occurs twice
per glucose molecule
• It finishes the same as it starts (4C oxaloacetate)
• Acetyl CoA (2C) enters at top & combines with the 4C oxaloacetate
to form a 6C compound called citric acid
• 2 decarboxylation reactions peel 2 carbons off again and CO2
molecules are formed

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The TCA / Kreb cycle/
Citric acid cycle

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 6C 2C

6C

4C

5C

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The TCA

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THE TCA

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What happens in the cycle?
• During the cycle, oxidation occurs when NAD+ accepts
electrons in three sites and FAD accepts electrons once.
• There is formation of one ATP per every turn of the cycle and
it turns twice per glucose.
• By the end of the citric acid cycle, the six carbon atoms in
glucose become CO2.
• The transition reaction (pyruvate decarboxylation) produces
two CO2, and the citric acid cycle produces four CO2 per
molecule of glucose.
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Products of the Krebs Cycle
• Energy stored in bonds is released step by step to form several reduced
coenzymes (NADH & FADH2) that curries the energy to the ETC

• 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
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 Citric acid cycle inputs and outputs per
glucose molecule
•Inputs: •Outputs:
•2 acetyl groups •4 CO2
•6 NAD+ •6 NADH
•2 FAD •2 FADH2
•2 ADP + 2 P •2 ATP

½ of the above per cycle

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 Enzymes
• PDH
• IDH
• Alpha KGDH

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Generation of NADH and FADH2 PER GLUCOSE
10 NADH
2 FADH2

Occurs in the following pathways;

i. Glycolysis

ii. Formation of acetylCoA

iii. The TCA

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 The TCA is linked to many other metabolic pathways
Glucose

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Entry points for various nutrients

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Chain
• The NADH and FADH2, formed during glycolysis, β-oxidation and the
TCA cycle, give up their electrons to reduce molecular O2 to H2O.
• Electron transfer occurs through a series of protein electron
carriers, the final acceptor being O2.
• ETC takes place in inner mitochondrial membrane where all of the
electron carriers are present.
• The function of ETC is to facilitate the controlled release of free
energy that was stored in reduced cofactors (NADH and FADH2)
during catabolism.

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The Electron Transport Chain – Closer look

• It involves a series of integral

membrane proteins in the inner
mitochondrial membrane capable of
oxidation and 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

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• Energy used to Pump H+
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Oxidation of NADH / FADH2

NADH + H+ NAD+ + 2H + + 2e -

FADH2 FAD+ + 2H + + 2e -

High energy electrons are released

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Chemiosmosis
• Small amounts of energy is 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
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 A Summary of the Energy Yield of Aerobic
Metabolism

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 THANK YOU FOR YOUR ATTENTION

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