Key points and terms to know about Glycolysis and Cellular Respiration!
Do not memorize all of the metabolic intermediates and their chemical
structures!! But do know the facts and concepts outlined here.
Remember change in Free Energy (∆G)? The overall equation for the
catabolism of glucose is:
C6H12O6 + 602 → 6CO2 + 6H2O ; ∆G = -686 kcal
2878 kcal ⏐ 3564 kcal
-686 kcal = a lot of free energy released (lost) – but some is stored (in ATP)!
Cells have found a way to oxidize (see below) molecules and harvest the free
energy loss by storing some of that energy in the form of ATP = Major
cellular currency! (Note that these same basic metabolic processes break
down and extract energy from other biomacromolecules, like proteins and
The key to Cellular Metabolism is the Oxidation-Reduction Reaction
Oxidation : loss of electrons
Reduction : gain of electrons
In redox, electrons move to lower potential energy states, and energy
is released (since energy must be conserved—the first law of
thermodynamics!). In a polysaccharide, for example, many of carbon’s
electrons are at a high potential energy state, since they are shared in
nonpolar covalent bonds between two atoms with similar electronegativity (H
and C). This means that the carbon’s electrons are not held very close to
either atom, and is also why gasoline, a hydrocarbon, is such a great fuel—
there is a lot of energy stored in its many C-H bonds. If the polysaccharide
(or hydrocarbon, etc.) undergoes a chemical reaction and the C ends up
bonded to O, which is much more electronegative, a polar covalent bond is
formed, and the carbon’s electrons are drawn very close to the oxygen.
Electrons near a very electronegative atom are at a lower potential energy
state than electrons near less electronegative atoms, so a lot of energy is
released in this reaction. In the equation above, the carbons in sugar start
out in a relatively reduced state, but they end up very oxidized (their
electrons drawn strongly away—though not removed!-- by the very
electronegative oxygen in CO2).
You should note that carbon can occur in a range of relatively reduced to
relatively oxidized forms:
-C- → -C-OH → -C=O → -C-OH → O=C=O
If the catabolic reaction to break down glucose happened all at once
(as it is written on the previous page), all that energy would be released as
heat. Not only would we be unable to harness that energy fast enough to do
cellular work, but we would also burst into flames! Instead, cells use what I
have called “the slow burn”–-a sequence of glycolysis and cellular respiration-
-to extract the energy from macromolecules slowly, in a stepwise fashion,
and store some of it in ATP for short-term future use. Note that this is
also a relatively “cold burn”, thanks to enzymes lowering the activation
energy, and the gradual, stepwise release of energy. What catabolism
shares with fire is that reactants are relatively reduced, and products leave
relatively oxidized, and energy is released (including some heat) as a result.
Cellular catabolic metabolism proceeds through three main pathways in
animals: glycolysis, the Krebs cycle, and oxidative phosphorylation (the
last two together are referred to as cellular respiration).
Glycolysis: To extract the energy from glucose (ONE 6C sugar), it is broken
down into pyruvate (TWO 3C sugars) in cytoplasm.
Consume (2) and make (4) ATP along the way (substrate level
phosphorylation to make ATP); also make 2 NADH. Redox reaction
(glucose oxidized, NAD+ reduced),
Overall glycolysis reaction:
1 glucose + 2ADP+ 2Pi + 2NAD 2 pyruvates + 2 ATP + 2 NADH
This is the only pathway of the three that does not require oxygen!
If oxygen is not present, after glycolysis, the 2 pyruvates undergo
fermentation (either lactic acid or alcoholic) to extract further
energy. This process does not produce as many ATP as cellular
respiration and requires constant regeneration of NADH to create any
ATP at all.
If oxygen is present, the 2 pyruvates next enter the cellular respiration
pathway, which uses two pathways (Krebs cycle and electron transport
chain) to convert 2 pyruvates into CO2 and H2O.
Krebs Cycle (= citric acid cycle): To enter the Krebs cycle, 2 pyruvates
first undergo a Transition Reaction:
2 pyruvates (3C) 2 acetyl CoA molecules (2C) + 2 NADH.
Acetyl CoA is the input molecule into the cycle part of the Krebs cycle, and
preserves the two “best” (highest-energy) carbons on a carrier (CoA).
Attaching Coenzyme A is to sugars reduces the stability (increases
the reactivity) of the bonds, encouraging further oxidation.
In eukaryotes, both the NADH and the acetyl CoA now enter the
mitochondria from the cytosol (bacteria do all of cellular respiration
in the cytosol!).
In mitochondrial matrix (= lumen = intracellular space):
Acetyl CoA (2C) is joined with OAA (4C) to make citric acid or citrate (6C).
The 4C sugar is regenerated at the end of the Krebs cycle.
Overall Krebs cycle reaction (1 glucose makes 2 pyruvate, so 2 acetyl CoA’s
enter the Krebs cycle):
2 acetyl group (2 C) + 2ADP + 2Pi + 6NAD+ + 2FAD
4CO2 + 2ATP + 6NADH + 2FADH2
Redox rxn (AcetylCoA oxidized, NAD+ and FAD reduced), substrate level
phosphorylation to make 2ATP
Oxidative phosphorylation – Passes e- & H+ from NADH & FADH2 (from
glycolysis and the Krebs cycle) to the electron transport chain (a
series of enzymes and electron carriers in the cristae of the
mitochondria). These e- and H+ are eventually passed to O2 to make
H2O (oxygen is the final electron acceptor of respiration—see our
equation at the beginning of the handout!).
Overall electron transport chain equation:
½ O2 + 2e- + 2 H+ H2O
ATP synthase is an enzyme in the mitochondrial inner membrane that
harnesses the energy of the H+ gradient that results from the electron
transport chain to regenerate ATP (see chemiosmosis, below).
ATP NADH FADH2
Glycolysis: 2 2
Krebs cycle: 2 8* 2
Electron Transport: 32-34**
Grand Total: 36-38 ATP
*note: after the transport of pyruvate (3C) into the matrix of the
mitochondrion, NAD+ is reduced to NADH, and pyruvate goes from 3C to 2C
and is then modified with CoA (acetyl-CoA), which makes it a more reactive
species. That is combined with 4C sugar to make 6C sugar!
**Because the NADH from glycolysis can donate its electrons to either
NAD+ or FAD in mitochondria. If it donates to NAD+, you get 34 ATP; if it
donates to FAD, you get 32 ATP.
Kinase – protein that transfers phosphate (for example, from ATP or Pi to
another molecule, such as a sugar or protein).
Substrate-level phosphorylation - the reverse of the example above- a
kinase transfers phosphate from substrate molecule to ADP,
Oxidative phosphorylation – kinase transfers phosphate from cellular pool of
free inorganic phosphate (Pi) to ADP, regenerating ATP.
Electron Carriers: in cellular respiration, stepwise oxidation of substrates is
carried out by molecules that accept electrons, primarily the
Coenzymes NAD+ and FAD (which are reduced to NADH and FADH2).
Chemiosmosis—Happens at the end of the electron transport chain, when
electrons have been pumped into the mitochondrial intermembrane
space (between inner and outer lipid bilayers). H+ ions move down the
concentration gradient, in across the inner mitochondrial membrane,
through ATP synthase, a channel-shaped enzyme. This movement
releases energy which is harnessed to make ATP through oxidative
Catabolic pathways – you should be able to explain why is energy both lost
and stored during the catabolism of glucose, and which change is