Lecture Sixteen: METABOLIC ENERGY:
GENERATION
AND STORAGE
(Figures in red are for the 7th Edition)
[Based on
Chapter 15
Berg,
Tymoczko
& Stryer]
 Two major questions integral to Biochemistry:
 How do cells extract energy and reducing power
from their environment?
 How do cells synthesise the building blocks of their
macromolecules?
 Answering here mainly the first question
 IMPORTANT NOTE:
 Although metabolic reactions may look complicated
the number of kinds of reaction is small and metabolic
pathways are regulated in very similar ways
 A Thermodynamically Unfavourable Reaction Can Be
Driven By A Favourable One
 A reaction can occur spontaneously __________ (the change
in free energy) is __________  ( -G )
 However the overall free-energy change for a coupled
series of reactions is the ______ of the free-energy
changes of the individual steps
 So a thermodynamically favourable reaction (-G)
can drive a thermodynamically unfavourable
reaction (+G) coupled to it
 There are three ways in which the reactions can be coupled
 A shared chemical intermediate (Eg: ___________ and
substrate level phosphorylation)
 An activated protein conformation (Eg: ___________
________)
 Ionic (electrochemical) gradients across membranes
(Eg: oxidative phosphorylation)
 Figure 15-8, page 417 (15-8, page 451)
 What Is Energy Required For?
 __________
 Active transport of solutes across membranes against
their concentration and/or charge gradient
 Biosynthesis
 Signal Amplification
 What Is Energy Obtained From?
 Oxidation of foodstuffs (chemotrophs)
 Trapping light energy (phototrophs)
 Part of this obtained energy is changed into (stored as) a
highly accessible form before it is used
 This store in most energy-requiring systems is
Adenosine Triphosphate (ATP)
 Figure 15-3, page 412 (15-3, page 447)
 ATP is an ______________ molecule
 It is an energy carrier containing two
PHOSPHOANHYDRIDE BONDS
 A large amount of energy (~G -12kcal/mol) is released
when ATP is hydrolysed to ADP and phosphate (Pi)
 And exactly the same is stored when ATP is
synthesised
 So the cycling between ATP and ADP is the
fundamental mode of energy exchange in
biological systems the ENERGY CURRENCY
 ATP Is Continuously Formed And Consumed
 ATP is _______ as a long term store
 A typical cell consumes ATP within ONE minute of
its formation therefore turnover of ATP is very high
 A resting human consumes ~40 kg of ATP/24 hrs
 ATP is an example of an ____________________
 The group carried is the phosphoryl group
 Note: ATP does NOT have special bonds, other than that
large amounts of energy are released when they are
hydrolysed under cellular conditions
 NADH and FADH2 are further examples of Activated
Carriers
 These two molecules are the major electron
carriers in the oxidation of fuel molecules
 Chemotrophs derive free energy from oxidation of fuel
molecules, such as glucose and fatty acids
 In aerobic organisms the ultimate electron acceptor
is oxygen, BUT
 The electrons from the fuel molecules are NOT
transferred directly to oxygen, but are instead
transferred to special electron carriers
 Pyridine nucleotides (i.e. ________)
 Or flavins (FADH2)
 These reduced electron carriers then transfer their
electrons to oxygen
 Via an electron transport chain located in the
inner mitochondrial membrane (IMM)
 The energy released is used to synthesise ATP
(a process known as oxidative
phosphorylation)
 Figure 15-13, page 420 (15-13, page 454)
+
 Nicotinamide adenine dinucleotide (NAD is a major
electron acceptor in the oxidation of fuel molecules
+
+
 In the oxidation of a substrate NAD accepts an H and
two e, (equivalent to a hydride ion, H  ), to form
NADH
 NOTE: NADH is used primarily for the generation of ATP
 The reduced form of NADP+ is NADPH
 Used almost exclusively for biosynthesis
 This needs reducing power in addition to ATP
 The other major electron carrier in the oxidation of fuel
molecules is flavin adenine dinucleotide (FAD)
 Figure 15-14, page 421 (15-14, page 455)
 The reactive part of FAD is the isoalloxazine ring
+
 This accepts two e and two H (equivalent to two
hydrogens) to form FADH
2
 Figure 15-15, page 421 (15-15, page 455)
 NADH, NADPH and FADH are slowly to react with
2
oxygen and ATP is only slowly hydrolysed
 Catalysts (enzymes) are required to speed these
processes
 So these enzymes can control the flow of free
energy and reductive power
 General: ________________________
 TABLE 15-2 page 422 (TABLE 15-2, page 456)
 The essential message here is:
 Most interchanges of activated groups in metabolism
are accomplished by a rather small set of carriers
 Stages In The Extraction Of Energy From Foodstuffs
 Hans Krebs described three stages in the extraction of
energy from foodstuffs
 Figure 15-12, page 419 (15-12, page 455)
 STAGE 1
 Large molecules of food broken into smaller units
 Proteins to amino acids
 Polysaccharides to simple sugars (eg _________ )
 Fats to glycerol and fatty acids
 NOTE: No useful energy is generated in this stage
 STAGE 2
 These numerous small molecules are degraded to a few
simple units that play a central role in metabolism
 Most are converted to acetyl CoA
 NOTE: Some ATP is generated at this stage
 STAGE 3
 Citric acid cycle and oxidative phosphorylation
 NOTE: 90% of ATP is generated in this
last stage
 Metabolic Pathways Are Regulated In
Three Principal Ways
 By controlling:
 The amounts of ______________
 Amount depends on rate of synthesis and rate of
breakdown
 The amount of most enzymes is regulated
primarily by adjusting the rate of
transcription of genes encoding them
 The catalytic activities of these ____________
 Controlled in several ways
 a) Reversible allosteric control
 b) Reversible covalent modification
 The accessibility of ______________
 For example by controlling their entry into the cell
 And finally:
 An important general principle of metabolism is:
 Biosynthetic and Degradative pathways are
almost always distinct  NOT THE SAME
 Many reactions in metabolism are controlled by
the ENERGY STATUS of the cell
 One measure of the energy status of the cell
is the balance between concentrations of ATP
and AMP within the cell, known as the
ENERGY CHARGE
 i.e.:
[ATP] + 1/2 [ADP]
energy charge =
[ATP] + [ADP] + [AMP]
 Summary of Lecture Sixteen
 Coupling a favourable one with an unfavourable reaction
can drive the latter
 Three ways
 The free energy donor and store in many systems is:
 ATP
 Continuously being consumed (high turnover)
 NADH and FADH2 are major electron carriers
 Ultimate electron carrier is Oxygen
 NADH and FADH2 electron transfer occurs in
the mitochondrial membrane
 Activated Carriers
 Interchanges in metabolism use a small select number
of carriers for the process
 Energy from Foodstuffs
 Three stages
 Principal is STAGE 3 => Produces 90% of ATP
 Metabolic Pathway Regulation
 Three principal ways