Glycolysis, Krebs Cycle,

and other Energy-

Releasing Pathways
 stages of cellular
respiration
 glycolysis
 Kreb’s cycle
 electron transport/oxidative
phosphorylation
What is Cellular Respiration?
 A process in which the energy in glucose is transferred to
ATP
 Cells use ATP to supply their energy needs
 Cellular Respiration
 Glucose is oxidized (releasing energy) and oxygen is
reduced to form water
 The carbon atoms of the sugar molecule are released
as carbon dioxide (CO2)
 The complete breakdown of glucose to carbon
dioxide and water requires two major steps:
1)Glycolysis - produces two ATP
2)Aerobic respiration - thirty-four more ATP
– In the absence of oxygen, fermentation
reactions produce alcohol or lactic acid but no
additional ATP
 GLYCOLYSIS
 glyco = sugar; lysis = breaking
Goal: breaks glucose down to form two
pyruvates (main pathway)
Who: all life on earth performs glycolysis
Where: in the cytosol
 Glycolysis produces 4 ATP's and 2 NADH,
but uses 2 ATP's in the process for a net of
2 ATP and 2 NADH
 Biomedical importance
Deficiency of enzymes of glycolysis can lead
to diseases
 Hemolytic anemias
 Fatigue (skeletal muscles)
 Ischemia
 Hypermetabolism in cancer cachexia
 Lactic acidosis
 The First Stage of Glycolysis
2. Produces 2 molecules; dihydroxyacetone
phosphate and Glyceraldehyde-3-Phosphate

Phosphofructokinase
Phosphohexose
Hexokinase isomerase
Glucokinase

Aldolase

1. glucose is phosphorylated,
converted to fructose, and then
fructose is phosphorylated Phosphotriose isomerase
 The Second Stage of Glycolysis
1. Gly-3-P is oxidized by NAD+ and phosphorylated with Pi
producing 1,3-bisphosphoglycerate and NADH
Phosphoglycerate
mutase
Phosphoglycerate Pyruvate
Enolase
kinase kinase

2. Phosphates are transferred to ADP producing

ATP in two different steps

3. Final product is 2 x (Pyruvate + 2 ATP + NADH)

 Final steps
 NADH must be
oxidized to NAD+ ==>
(enol) (Keto)
depend upon whether
O2 is available
 ANAEROBIC
– Pyruvate is reduced by
NADH to Lactate and
NAD+
 AEROBIC
– Pyruvate transported to
mitochondrion
 Anaerobic Respiration
 Goal: to reduce pyruvate, thus generating NAD+
 Where: the cytoplasm
 Why: in the absence of oxygen, it is the only
way to generate NAD+ and ADP

Alcohol
Fermentation
• Occurs in yeasts in
many bacteria
•The product of
fermentation, alcohol, is
toxic to the organism
 Anaerobic Respiration
 Lactic Acid
Fermentation -
occurs in humans and
other mammals
– The product of Lactic
Acid fermentation,
lactic acid, is toxic to
mammals
– This is the "burn" felt
when undergoing
strenuous activity
 Aerobic Respiration
 The process by which a cell uses O2 to
"burn" molecules and release energy
 The reaction:
C6H12O6 + 6O2 >> 6CO2 + 6H2O
 NAD+ and FAD carry electrons to the
electron transport system
 The Citric Acid Cycle
 Tricarboxylic Acid (TCA) Cycle or the Krebs
Cycle
 Goal: take pyruvate and put it into the Krebs
cycle, producing NADH and FADH2
: provide substrate for respiratory chain
 Where: the mitochondria
 There are two steps
(1) The Conversion of Pyruvate to Acetyl CoA
(2) The Krebs Cycle proper
 The Citric Acid Cycle
 All of Carbons, Hydrogens, and Oxygen in
pyruvate end up as CO2 and H2O
 The Krebs cycle plus the conversion of
pyruvate produces;
– 2 ATP's
– 8 NADH's
– and 2 FADH2's
…….. per glucose molecule
 B vitamins essential in the Citric
acid cycle
 RIBOFLAVIN - flavin adenine dinucleotide (FAD)
– A cofactor for succinate dehydrogenase
 NIACIN - nicotinamide adenine dinucleotide
(NAD)
– Electron acceptor for isocitrate dehydrogenase, -
ketoglutarate dehydrogenase, and malate
dehydrogenase
 THIAMIN (Vitamin B1) – thiamine diphosphate
– Coenzyme for decarboxylation in the -ketoglutarate
dehydrogenase reaction
 PANTOTHENIC ACID - coenzyme A (CoA)
– The cofactor attached to the “active” carboxylic acid residues
such as acetyl-CoA and succinyl CoA
 Kreb’s cycle animation
 http://www.science.smith.edu/department
s/Biology/Bio231/krebs.html
The Conversion of Pyruvate to Acetyl
CoA for Entry Into the Krebs Cycle
 Kreb’s cycle summary

When acetyl CoA

attaches to a C4
molecule in the Krebs
cycle, the Coenzyme
A is released

Two acetyl CoA

molecules are
consumed to
produce 4 CO2,
2ATP, 6 NADH
and 2 FADH2
Kreb’s cycle summary
 ATP is produced by
substrate level
phosphorylation
– production of ATP
using energy from
other high-energy
compounds but
without the use of
the electron
transport system in
the mitochondria
Summary
 Electron Transport and
Oxidative Phosphorylation
 Goal : to break down NADH and FADH2, pumping H+ into the outer
compartment of the mitochondria
 Where : the mitochondria
 Electron Transport System
 It consists of a series of carrier molecules which
pass electrons from a high-energy compound to
a final low-energy electron acceptor
 Energy is released during these oxidation-
reduction reactions to produce ATP
 NADH and FADH2 are used to produce ATP as
electrons are passed from one carrier to another
 Eventually the electrons combine with hydrogen
ions and oxygen (reduction) to form water
 Electron Transport System
 ETS creates a gradient which is
used to produce ATP
 ATP is generated as H+ moves
down its concentration gradient
through a special enzyme called
ATP synthase
 Oxygen is the final electron
acceptor
 The low-energy electrons that
emerge from the electron
transport system are taken up
by O2. The negatively charged
oxygen molecules take up
protons from the medium and
form water (2H+ + 2e- + ½ O2
→ H2O)
 Electron Transport
Phosphorylation typically
produces 32 ATP's
Electron Transport System
 Total ATP yield per glucose
Conversions
 NADH produced in the cytoplasm produces two ATP by the electron
transport system
 NADH produced in the mitochondria produces three ATP.
 FADH2 adds its electrons to the electron transport system at a lower level
than NADH, so it produces two ATP.
Glycolysis
– 2 ATP
– 2 NADH (= 4 ATP; these are converted to ATP in the
mitochondria during cellular respiration)
Formation of Acetyl CoA
– 2 NADH (= 6 ATP)
Krebs Cycle
– 6 NADH (= 18 ATP)
– 2 FADH2 (= 4 ATP)
– 2 ATP
* 12 ATP’s are yielded per turn (18 + 4 + 2 = 24/2 =12)
Pathway Substrate-Level Oxidative Total
Phosphorylation Phosphorylation ATP

Glycolysis 2 ATP 2 NADH = 4 - 6 6 - 8*

ATP*
* In animals

CoA 2 NADH = 6 ATP 6

Krebs Cycle 2 ATP 6 NADH = 18 ATP 24

2 FADH2 = 4 ATP

TOTAL 4 ATP 32 ATP 36 – 38

 Beta Oxidation
 Fats consist of a glycerol backbone with two or three
fatty acids connected to it
 The body absorbs fats and then breaks off the fatty
acids from the glycerol
 Glycerol is converted to glyceraldehyde phosphate, an
intermediate of glycolysis
 The fatty acids are broken down into two-carbon units
which are then converted to acetyl CoA
– An eight-carbon fatty acid can produce 4 acetyl CoA's
– Each acetyl CoA is worth 12 ATP's (3 NADP, 1 FADH2, 1 ATP)
– Therefore, this short fatty acid is worth 48 ATP's, a fat with
three chains of this length would be worth 144 ATP's!
– This is why fats are such a good source of energy, and are hard
to lose if you want to lose weight
Other Uses for Molecules used in
Glycolysis and the Krebs Cycle
 Not all of the molecules that enter
Glycolysis and the Krebs Cycle are used
for energy
 Some are used to synthesize fats,
nucleotides, amino acids, and other
biologically important molecules