BIOCHEMISTRY - VII

Biochemical energetics
• Energy: the capacity to do work

-kinetic energy: the energy of motion

-potential energy: stored energy

• Energy can take many forms: chemical, mechanical, electric

current, heat, light
First Law of Thermodynamics – energy cannot be created or
destroyed
-energy can only be converted from one form to another

For example:

sunlight energy photosynthesis chemical energy

• Second Law of Thermodynamics: disorder is more likely than order

Entropy(S): disorder in the universe

• The 2nd Law of Thermodynamics states that entropy is always increasing.

• Energy is required to keep order, to do work

- keep cells together and organized
- perform life processes
•Enthalpy (H): All of the energy contained in a molecule’s chemical
bonds

• Free energy: the energy available to do work, to reduce

disorder(enthalpy)
- denoted by the symbol G (Gibb’s free energy)

• free energy = enthalpy – (entropy x temp.)

ΔG = ΔH – T x ΔS
• Chemical reactions can create changes in free energy:
ΔG = ΔH – T x ΔS

• When products of chemical reactions contain more free energy

than reactants – ΔG is positive.

• When reactants contain more free energy than products –is ΔG

negative.
•Chemical reactions can be described by the transfer of energy that
occurs:

• endergonic reaction: a reaction requiring an input of energy

• ΔG is positive

• exergonic reaction: a reaction that releases free energy

• ΔG is negative
1
0
 ΔG < 0 - the reaction goes spontaneously in the forward
direction (R → P)
- ΔG has a high negative value → the reaction is
irreversible
 ΔG = 0 - the reaction is at equilibrium (R ↔ P)
 ΔG > 0 - the direction is R ← P
- the direction R → P is possible only if energy is added to
the system (from an exergonic reaction)
•Most reactions require some energy to get started - activation
energy.

• activation energy: extra energy needed to get a reaction started

-destabilizes existing chemical bonds
-required even for exergonic reactions

• catalysts: substances that lower the activation energy of a reaction

(enzymes)
Reaction: A ↔ B

• Gibbs equation: ΔG = ΔG⁰ + RT ln [B]/[A]

• ΔG⁰-Standard free energy change
• ΔG depends on the real concentration of reactants and products inside cells
• at the equilibrium point:
ΔG = 0 => ΔG⁰ = – RT ln [B]eq/[A]eq => ΔG⁰ = – RT ln Keq

- ΔG⁰ is a constant and is characteristic for each reaction

- ΔGglobal = ΔG1 + ΔG2 + ΔG3 + ΔG4 + .....

- if ΔGglobal < 0 → the pathway is globally exergonic

and takes place in the figured direction, even if some
individual reactions have ΔG > 0
Phosphate can be transferred from compounds
with higher ΔG to those with lower ΔG.

Reactions such as :

PEP + ADP => Pyruvate + ATP

are favorable, and can be used to synthesize ATP.

- the flow of phosphoryl groups, represented by P, from

high-energy phosphoryl group donors via ATP to acceptor
molecules (such as glucose and glycerol) to form their low-
energy phosphate derivatives. (The location of each
compound’s donor phosphoryl group along the scale
approximately indicates the ΔG° of hydrolysis.) This flow of
phosphoryl groups, catalyzed by kinases, proceeds with an
overall loss of free energy under intracellular conditions.
Hydrolysis of low-energy phosphate compounds releases Pi,
which has an even lower phosphoryl group transfer
potential.
• Potential energy stored in chemical bonds can be transferred from
one molecule to another by way of electrons.

oxidation: loss of electrons

reduction: gain of electrons

• Redox reactions are coupled to each other.

 Oxidation-Reduction Reactions

• A chemical reaction that transfers electrons from one

atom to another
• Oxidation = loss of an electron
• Reduction = gain of an electron
 Oxidation-Reduction Reactions

• Oxidation
• A chemical reaction in which a molecule gives up
electrons
• Oxidation releases energy
• The molecule loosing the electron is oxidized
 Oxidation-Reduction Reactions

• Reduction:

• A chemical reaction in which a molecule gains

electrons and energy
• The molecule that accepts electrons is reduced
• The molecule being reduced receives energy
Oxidation-Reduction Reactions

- If it Looses Electrons during the reaction, it’s Oxidized

- If it Gains Electrons during the reaction, it’s Reduced
NAD+ and NADP+

- derived from vitamin PP-

(Vitamin B-3)

- Is nicotinamide adenine
dinucleotide.
Contains ADP, ribose, and
nicotinamide.
Reduces to NADH when the
nicotinamide group accepts
H+ and 2e-.
FMN and FAD

(flavin mononucleotide and

flavin adenine dinucleotide)

- derived from vitamin B2

(riboflavin)

Contains ADP and

riboflavin (vitamin B2).

- accepts 2 electrons in the

form of 2 hydrogen atoms
1. nicotinamide coenzymes:

AH2 + NAD(P)+ → A + NAD(P)H + H+ [ NAD(P)+ + 2e− + 2H+ → NAD(P)H + H+ ]

2. flavin coenzymes:
AH2 + FMN/FAD → A + FMNH2/FADH2 [ FMN/FAD + 2e− + 2H+ → FMNH2/FADH2 ]
ATP
• ATP is the molecule that cells use to store, transfer, and
provide energy
• The energy from ATP is used to fuel anabolic reactions
• recall: for growth, repair, and reproduction
• ATP = Adenosine Triphosphate
• Adenosine (same molecule from DNA and RNA)
+
• Three inorganic phosphates (functional group PO 4)
ATP - 1 PO4 = ADP (Adenosine
Diphosphate)

ADP - 1 PO4 = AMP (Adenosine

Monophosphate)

ADP + 1 PO4 = ATP

•When the bond between phosphates is broken:
ATP ADP + Pi
energy is released
• ADP = adenosine diphosphate
• Pi = inorganic phosphate
• This reaction is ireversible...
•When the bond between phosphates is formed:
ADP + Pi ATP
energy is consumed
ATP

ADP
CYTOPLASM

NADH
Electrons NADH FADH2
carried by NADH

Glycolysis Oxidative
Pyruvate Citric Acid Phosphorylation
Glucose Pyruvate
Oxidation Cycle (electron transport
and chemiosmosis)

Mitochondrion

ATP
ATP ATP

Substrate-level Substrate-level Oxidative

phosphorylation phosphorylation phosphorylation
Oxidative phosphorylation
• Oxidative phosphorylation is the culminating point of energy
yielding metabolism in aerobic organisms (in mitochondria)
• has two components:
- the electron transport chain (respiratory chain) - transfers
the electrons from NADH and FADH2 to O2, with the formation
of H2O (the exergonic component)
- ATP synthesis by the phosphorylation of ADP, catalyzed by
ATP synthase (the endergonic component)
• The respiratory chain (in the inner mitochondrial membrane):
- Flavoproteins (containing tightly bound FMN or FAD)
- Coenzyme Q (ubiquinone)
- Iron-sulfur proteins
- Cytochromes
 Ubiquinone (coenzyme Q)
- lipid-soluble benzoquinone with a long isoprenoid side chain

Iron-sulfur proteins
- Fe in association with S atoms (inorganic/belonging to Cys residues)
• Complexes I and II catalyze electron transfer to ubiquinone from
two different electron donors:
- NADH (Complex I)
- succinate (Complex II) - an intermediate of a catabolic
pathway called Krebs cycle
• Complex III carries electrons from reduced ubiquinone to
cytochrome c
• Complex IV finally transfers electrons from cytochrome c to O2
Inhibitors of electron transport
• ATP synthesis is achieved by ATP synthase (Fo-F1 complex):
- Fo is integrated in the inner mitochondrial membrane - it contains a H+
pore through which protons pass from the intermembrane space to the
matrix
- F1 is located on the internal side of inner mitochondrial membrane -
contains the catalytic site of ATP synthase
• a proton gradient is generated across the inner mitochondrial membrane
(higher [H+] outside and lower [H+] inside) – with two components: electrical
and chemical
• The proton influx causes the continuous removal of ATP from the catalytic site
once it results from the reaction catalyzed by ATP synthase (it drives a
rotational mechanism)
• is the chemiosmotic model
• Metabolism - the entire network of chemical
reactions carried out by living cells. Metabolism also
includes coordination, regulation and energy
requirement.
• Metabolites - small molecule intermediates in the
degradation and synthesis of polymers
A sequence of reactions that has a specific purpose (for instance:
degradation of glucose, synthesis of fatty acids) is called metabolic
pathway.
Metabolism Regulation
Feedback inhibition
• Product of a pathway controls the rate of its own synthesis by inhibiting an
early step (usually the first “committed” step (unique to the pathway)
• Feed-forward activation
• Metabolite early in the pathway activates an enzyme further down
the pathway
• Regulatory role of a protein kinase, amplification by a signaling
cascade
• The initial signal may be amplified by the “cascade” nature of this
signaling
 STAGES OF METABOLISM

CATABOLISM
Stage I. Breakdown of macromolecules (proteins, carbohydrates and
lipids to respective building blocks.
Stage II. Amino acids, fatty acids and glucose are oxidized to common
metabolite (acetyl CoA)
Stage III. Acetyl CoA is oxidized in citric acid cycle to CO2 and water.
As result reduced cofactor, NADH2 and FADH2, are formed which give
up their electrons. Electrons are transported via the tissue respiration
chain and released energy is coupled directly to ATP synthesis.
 Stages of Metabolism
Catabolic reactions:
Catabolism is characterized by convergence of three major routs toward a final
common pathway.
Different proteins, fats and carbohydrates enter the same pathway – tricarboxylic
acid cycle.

Anabolism can also be divided into stages, however the anabolic pathways are
characterized by divergence.
Monosaccharide synthesis begin with CO2, oxaloacetate, pyruvate or lactate.
Amino acids are
synthesized from acetyl CoA, pyruvate or keto acids of Krebs cycle.
Fatty acids are constructed from acetyl
CoA.
On the next stage monosaccharides, amino acids and fatty acids are used for the
synthesis of polysaccharides, proteins and fats.
Compartmentation of Metabolic Processes in Cell

• Compartmentation of metabolic processes permits:

- separate pools of metabolites within a cell
- simultaneous operation of opposing metabolic paths
- high local concentrations of metabolites
• Example: - fatty acid synthesis enzymes (cytosol),
- fatty acid breakdown enzymes (mitochondria)
References

•David L. Nelson, Michael M. Cox. Lehninger Principles of Biochemistry. 5th edition, 2008.
•Colleen Smith, Allan D. Marks, Michael Lieberman. Marks’ Basic Medical Biochemistry: A
Clinical Approach. 2nd edition, 2004.
•Robert K. Murray, Darryl K. Granner, Peter A. Mayes, Victor W. Rodwell. Harper’s
Illustrated Biochemistry. 27th edition, 2006.
•Pamela C. Champe, Richard A. Harvey, Denise R. Ferrier. Lippincott’s Illustrated Reviews
– Biochemistry. 4th edition, 2007.
•Reginald H. Garrett, Charles M. Grisham. Biochemistry. 2nd edition, 1999.
•Mary K. Campbell, Shawn O. Farrell. Biochemistry. 6th edition, 2007.