Pyruvate, Krebs, Electrans

Lec: Pyruvate, the Kreb’s Cycle and the Electron Transport Chain
Prepared by: Roy P. Maribojoc MD
Pyruvate is the end product of glycolysis in cells with mitochondria and with an adequate supply of
oxygen (aerobic glycolysis). This is summarized in the following reaction:
Glucose + 2 Pi + 2 NAD + 2 ADP ---------- 2 pyruvate + 2 ATP + 2 NADH + 2 H + H2O
Fates of Pyruvate
A. Reduction of pyruvate to lactate
 The final product of anaerobic glycolysis. In the absence of oxygen, glucose is converted
to pyruvate, which is reduced by NADH to form lactate. Therefore, there is no net
formation of NADH during anaerobic glycolysis.
 Enzyme: lactate dehydrogenase
 Important in RBC, WBC (and other cells with few or no mitochondria) and in skeletal
muscle during intense exercise).
 Physiologically, reversible in tissue with a low NADH/NAD+ , for example, liver and heart
muscle.
 Located in the cytosol.
B. Carboxylation of pyruvate to oxaloacetate

 Enzyme: pyruvate carboxylase
 Biotin serves as prosthetic group
 Activated by acetyl CoA
 Replenishes intermediates of the TCA cycle.
 Provides substrates for gluconeogenesis.
 An irreversible reaction
 Located in mitochondria.
C. Reduction of pyruvate to ethanol (microorganisms)

 ethanol synthesis
 Enzyme: pyruvate decarboxylase
 Occurs in yeast and some bacteria (including intestinal flora)
 Thiamine pyrophosphate-dependent pathway.
 Located in the cytosol.
D. Oxidative decarboxylation of pyruvate.

 Enzyme: pyruvate dehydrogenase complex
 Thiamine-PP, lipoic acid, FAD, NAD+ and CoA serve as coenzymes.
 Source of acetyl CoA for TCA and fatty acid synthesis.
 An irreversible reaction.
 Located in mitochondria.
Conversion of pyruvate to Acetyl CoA
 2 per glucose
 Oxidative decarboxylation
 Makes NADH
1/7
CO2
(Thiamine-PP)
Ethanol
acetaldehyde PYRUVATE lactate
NADH+H+
CO2 NADH+H+
+ NADH+
NAD
+
NAD
CO2
NADH+H+
oxaloacetate Acetyl CoA
2/7
Sources of Acetyl CoA
Fates of Acetyl CoA

 if there is an energy need (In the presence of Carbohydrates),
o enters the Kreb’s cycle and is metabolized to CO2, NADH, FADH2,GTP and,
ultimately, ATP
 If energy not being used (Lots of ATP present)
o Made into fat
 If energy being used, but no carbohydrates present
o Starvation
o Forms ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone) which
can provide energy to the peripheral tissues. However, elevated level of ketone
bodies in the blood results in acidemia (ketoacidosis).
3/7
The Krebs Cycle (refer to the diagram for the entire reaction)
• (aka, Tricarboxylic Acid (TCA) Cycle, Citric Acid Cycle)
“The wheel is turnin’ and the sugar’s a burnin’”
• Overall goal
 Makes ATP
 Makes NADH
 Makes FADH2
 Requires some carbohydrate to run
• Occurs in the matrix of the mitochondrion (The Citric Acid Cycle enzymes are found in the matrix of
the mitochondria)
Mitochondrion
Outer membrane, which is very permeable
Space between membranes called intermembrane space
Inner membrane (cristae)
Permeable to pyruvate,
Impermeable to fatty acids, NAD, etc
Matrix is inside the inner membrane
• 2-carbon (acetyl CoA) joins with a 4-carbon compound (oxaloacetate) to form a 6- carbon
compound called Citric acid. Citric acid (6C) is gradually converted back to the 4-carbon compound
to start the cycle once more (see attached diagram)
• The carbons removed are released as CO2
• The hydrogens, which are removed, join with NAD to form NADH2
• The cycle does not involve net consumption or production of oxaloacetate or of any other
intermediate.
Net From Kreb’s cycle

Acetyl CoA + 3NAD+ FAD + GDP + Pi + H2O --- 3NADH + FADH2 + GTP + CoA + 3H + 2CO2
• Oxidative process
– 3 NADH
– FADH2
– GTP
• All ultimately turned into ATP (oxidative phosphorylation)
4/7
Energy-Producing reaction Number of ATP produced
3 NADH - 3 NAD 9
FADH - FAD 2
GDP + Pi -GTP 1
Total 12 ATP/Acetyl CoA
• X 2 per glucose
– 6 NADH
– 2 FADH2
– 2 GTP
Therefore, a total of 24 ATPs can be produced in the Kreb’s cycle per one molecule of glucose
5/7
Electron Transport Phosphorylation (Chemiosmosis) The electron transport chain consists of protein
carriers, including NADH dehydrogenase, ubiquinones, cytochrome b-c1, cytochrome c, cytochrome
oxidase, and ATP synthase complex. This electron transport chain in cellular respiration will take the
energy stored in NADH and FADH2 during glycolysis and the Krebs cycle and convert it to chemical bond
energy in the form of ATP.
 . Electrons are passed from one carrier to the next, the energy is used to drive proton pumps.
 NADH and FADH2 lose their electrons, and the energy from those electrons is used to produce
ATP.
 Energy produced from movement of the protons back across the membrane is used by ATP
synthase to make ATP from ADP and phosphate.
 this reaction takes place on the inner mitochondrial membrane (cristae),
• oxygen serves as the final hydrogen acceptor, and it combines to form water
• Electrons flowing through the proteins of the electron transport chain must have
something to receive them at the end. If not, the flow of electrons is blocked. Oxygen
fills this role in cellular respiration. Oxygen molecules diffuse into the mitochondria, pick
up the electrons, and combine with the hydrogen ions present to form water, a product
of cellular respiration.
Carbon monoxide poisoning
• The presence of oxygen to accept electrons is critical for aerobic cellular respiration,
explaining why carbon monoxide kills so rapidly. Carbon monoxide binds to hemoglobin
more easily and with greater strength than oxygen. In a room full of carbon monoxide, your
blood quickly gets saturated with the gas. It's not the carbon monoxide that kills you, but
the process it sets up. Carbon monoxide (CO) has a much stronger attraction to the oxygen-
binding site on hemoglobin than oxygen does. The result is that it only takes a relatively
small amount of CO to tie up a large percentage of the hemoglobin making it unavailable to
pick up oxygen. The cells quickly become oxygen deficient, so the electrons back up in the
electron transport chain and the cells can't make ATP. A cell that can't make ATP cannot
survive and death occurs quickly.
• In aerobic prokaryotes, 38 ATP molecules can be produced form complete oxidation of a glucose
molecule in glycolysis, the Krebs cycle, and the electron transport chain.
• In eukaryotes, 36 or 38 ATP molecules are produced from complete oxidation of a glucose
molecule (in some tissues 2 ATP are required to shuttle the 2 electrons from the NADH
produced in glycolysis across the mitochondrial membrane to the electron transport chain, in
others there is no energy cost and 38 ATP are gained per mole of glucose).
6/7
Starting from glucose (via glycolysis), the stoichiometry is as follows, through the citric acid cycle:
Glucose + 2H2O + 10 NAD+ + 2 FAD + 4 ADP + 4 Pi ---> 6 CO2 + 10 NADH + 6 H+ + 2 FADH2 + 4 ATP
7/7

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Lec: Pyruvate, the Kreb’s Cycle and the Electron Transport Chain

Prepared by: Roy P. Maribojoc MD

B. Carboxylation of pyruvate to oxaloacetate

C. Reduction of pyruvate to ethanol (microorganisms)

D. Oxidative decarboxylation of pyruvate.

oxaloacetate Acetyl CoA

Fates of Acetyl CoA

Net From Kreb’s cycle

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