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Fate of Pyruvate

• Conversion of glucose to pyruvate leads to ATP

synthesis
• The pathway cannot stop at pyruvate
– redox balance will not be maintained

• NAD+ must be regenerated for glycolysis to proceed

Fate of Pyruvate

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Aerobic Exit of Glycolysis

• In the presence of oxygen:

• pyruvate enters mitochondria for aerobic ATP
production
• pyruvate is first converted to acetyl CoA

Pyruvate to Acetyl-CoA
• Pyruvate dehydrogenase complex is composed of
multiple copies of three enzymes:
• E1, pyruvate dehydrogenase (cofactor TPP)
• E2, dihydrolipoyl transacetylase
• E3, dihydrolipoyl dehydrogenase, (with its cofactors
FAD and NAD)

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Pyruvate to Acetyl-CoA

Pyruvate to Acetyl-CoA
• E1 catalyzes first the decarboxylation of pyruvate,
producing hydroxyethyl-TPP, and then the oxidation of
the hydroxyethyl group to an acetyl group
• E2 catalyzes the transfer of the acetyl group to
coenzyme A, forming acetyl-CoA.
• E3 catalyzes the regeneration of the disulphide
(oxidized) form of lipoate; electrons pass first to FAD,
then to NAD

• The Acetyl-CoA produced can then enter the TCA cycle

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TCA Cycle

• Importance of the TCA cycle:

1. Transfer of electrons from pyruvate to NAD+ to
form NADH (from FAD to FADH2)
• these electrons are a source of ATP synthesis in
ETC
2. Generate ATP/GTP
3. Generate metabolic intermediates for other
pathways

TCA Cycle
• Also called the Krebs cycle or the tricarboxylic
• Accounts for the majority of carbohydrate, fatty acid
and amino acid oxidation.
• It also accounts for a majority of the generation of
these compounds and others as well.
• Amphibolic:
• acts both catabolic and anabolic

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TCA Cycle
• In aerobic organisms, the TCA cycle is an amphibolic
pathway
• one that serves in both catabolic and anabolic
processes
• anaplerosis and cataplerosis
• Besides its role in the oxidative catabolism of
carbohydrates, fatty acids, and amino acids:
• the cycle provides precursors for many biosynthetic
pathways

TCA Cycle

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TCA Cycle
• The citric acid cycle enzymes are found in the matrix
of the mitochondria
• Substrates have to flow across the outer and inner
parts of the mitochondria

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TCA Cycle

TCA Cycle
• Products of the TCA Cycle

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TCA Cycle

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TCA Cycle
• Glycolysis produces pyruvate by oxidation of glucose
• The pyruvate is than oxidized to ACoA in the
mitochondria
• The ACoA units are oxidized to CO2 by TCA cycle in
the mitochondrial matrix
• Energy released during both the reactions are collected
by NAD+ and FAD
• NADH and FADH2 carry energy in the form of
electrons

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Cellular Respiration
• Cellular respiration occurs in three major stages:
1. Organic fuel molecules (glucose, fatty acids, and some
amino acids) are oxidized to yield two-carbon
fragments in the form of acetyl-coenzyme A (acetyl-
CoA).
2. Acetyl groups are fed into the citric acid cycle, which
enzymatically oxidizes them to CO2
• the energy released is conserved in the reduced
electron carriers NADH and FADH2.

Cellular Respiration
3. The reduced coenzymes are oxidized, giving up
protons (H+) and electrons
• The electrons are transferred to O2—the final
electron acceptor—via a chain of electron-carrying
molecules known as the respiratory chain

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Cellular Respiration

Electron Transport Chain

• Most of the ATP is generated through a series of electron
transporters undergoing redox reactions
• the Electron Transport Chain (ETC)
• Causing H+ ions to accumulate within the matrix space
• H+ forms a concentration gradient
• H+ diffuses out of the matrix space by passing through
ATP synthase
• The current of H+ ions powers the catalytic action of ATP
synthase, which phosphorylates ADP, producing ATP

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Electron Transport Chain

• ETC is the last component of aerobic respiration
• the only part of glucose metabolism that uses
atmospheric oxygen
• Oxygen diffuses into plants
• in animals O2 it enters the body through the
respiratory system.

• NADH and FADH2

• Electron carriers

Electron Transport Chain

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Electron Transport Chain

• Electron transport:
• series of redox reactions that resemble a relay race
• electrons are passed rapidly from one component to
the next
• at the endpoint, electrons are reduce by O2, producing
H2O2
• ETC consist of
• 4 complexes composed of proteins, labeled I-IV
• may not require oxygen in prokaryotes
• a common feature is the presence of a proton pump to
create a proton gradient across a membrane

Electron Transport Chain

• Complex I
• To start, two electrons are carried to the first complex
aboard NADH.
• Composed of flavin mononucleotide (FMN) and an iron-
sulfur (Fe-S)-containing protein.
• FMN, is derived from vitamin B2 (riboflavin)
• The enzyme in complex I is NADH dehydrogenase
• Complex I can pump 4 H+ across the membrane from the
matrix into the intermembrane space
• helping to establish H+ gradient

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Electron Transport Chain

• Q and Complex II
• Complex II directly receives FADH2
• Since FADH2 bypasses Complex I, fewer ATP is
produced
• 3 ATP’s are produced from 1 NADH
• 2 ATP’s are produced from 1 FADH2
• Ubiquinone (Q) connects Complex I and II to III
• Q is lipid soluble and freely moves through the
hydrophobic core of the membrane
• Once it is reduced, (QH2), Q delivers its electrons to the
next complex in the electron transport chain.

Electron Transport Chain

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Electron Transport Chain

• Complex III
• Complex III is also called cytochrome oxidoreductase
• Cytochrome proteins have a prosthetic group of heme
• The heme molecule is similar to the heme in
hemoglobin, but it carries electrons, not oxygen.
• Complex III pumps protons through the membrane and
passes its electrons to cytochrome c for transport to
Complex IV
• Cytochrome c is the acceptor of electrons from Q
• whereas Q carries pairs of electrons, cytochrome c
can accept only one at a time

Electron Transport Chain

• Complex IV
• Complex IV is composed of cytochrome proteins
• The cytochromes hold O2 very tightly, until the O2 is
completely reduced
• The reduced oxygen then picks up two hydrogen ions
from the surrounding medium to make water (H2O)
• The removal of the H+ from the system contributes to the
ion gradient used in the process of chemiosmosis.

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Electron Transport Chain

Chemiosmosis

Electron Transport Chain

• Chemiosmosis
• The free energy from the series of redox reactions is
used to pump H+ (protons) across the membrane
• The uneven distribution of H+ ions across the membrane
establishes both concentration and electrical gradients
• electrochemical gradient)
• due to the H+ positive charge and their aggregation on
one side of the membrane
• H+ cannot diffuse back across into the matrix
• H+ in the matrix space can only pass through an integral
membrane protein called ATP synthase

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Electron Transport Chain

• Chemiosmosis
• The protein complex acts as generator- turned by the
force of the H+ diffusing through it
• Facilitates the addition of a phosphate to ADP, forming
ATP
• using the potential energy of the H+ gradient.
• The production of ATP using chemiosmosis in the
mitochondria is called Oxidative Phosphorylation
• At the end of the pathway, the electrons are used to
reduce an oxygen molecule to oxygen ions.

Electron Transport Chain

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Cellular Respiration

• In general:
• 3 ATP’s are produced from 1 NADH
• 2 ATP’s are produced from 1 FADH2

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Cellular Respiration

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Cellular Respiration

2 ATP + 2 ATP + ~36 ATP

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Glycogen Metabolism
• Glycogenolysis:
• Pathway in which glycogen breaks down into
glucose-1-phosphate and glucose
• Reaction takes place in the hepatocytes and the
myocytes
• Glycogenesis:
• Glycogen synthesis
• Glucose molecules are added to chains of glycogen
for storage
• Activated during rest periods and insulin in response
to high glucose levels
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Glycogen Metabolism

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Gluconeogenesis

• The synthesis of new glucose

• proceeds essentially as a reversal of Glycolysis
• gluconeogenesis, however, uses four different
enzymes not found in glycolysis
• The process begins in the mitochondria with two of
the enzymes that are specific for the pathway

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Gluconeogenesis

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