Download Table of Contents - Milan Area Schools

Cellular Pathways that
Harvest Chemical Energy
7
Cellular Pathways that Harvest Chemical Energy
• Energy and Electrons from Glucose
• Glycolysis: From Glucose to Pyruvate
• Pyruvate Oxidation
• The Citric Acid Cycle
• The Respiratory Chain: Electrons, Protons, and
ATP Production
• Fermentation: ATP from Glucose, without O2
• Contrasting Energy Yields
• Relationships between Metabolic Pathways
• Regulating Energy Pathways
7
Energy and Electrons from Glucose
• The sugar glucose (C6H12O6) is the most
common form of energy molecule.
• Cells obtain energy from glucose by the chemical
process of oxidation in a series of metabolic
pathways.
7
Energy and Electrons from Glucose
• Principles governing metabolic pathways:
 Metabolic pathways are formed by complex
chemical transformations which occur in
separate reactions.
 Each reaction in the pathway is catalyzed by a
specific enzyme.
 Metabolic pathways are similar in all
organisms.
 In eukaryotes, many metabolic pathways are
compartmentalized in organelles.
 The operation of each metabolic pathway can
be regulated by the activities of key enzymes.
7
Energy and Electrons from Glucose
• When burned in a flame, glucose releases heat,
carbon dioxide, and water.
 C6H12O6 + 6 O2  6 CO2 + 6 H2O + energy
• The same equation applies for the biological,
metabolic use of glucose.
7
Energy and Electrons from Glucose
• About half of the energy from glucose is collected
in ATP.
• G for the complete conversion of glucose is
–686 kcal/mol.
• The reaction is therefore highly exergonic, and it
drives the endergonic formation of ATP.
7
Energy and Electrons from Glucose
• Three metabolic processes are used in the
breakdown of glucose for energy:
 Glycolysis
 Cellular respiration
 Fermentation
Figure 7.1 Energy for Life
7
Energy and Electrons from Glucose
• Glycolysis produces some usable energy and
two molecules of a three-carbon sugar called
pyruvate.
• Glycolysis begins glucose metabolism in all cells.
• Glycolysis does not require O2; it is an anaerobic
metabolic process.
7
Energy and Electrons from Glucose
• Cellular respiration uses O2 and occurs in
aerobic (oxygen-containing) environments.
• Pyruvate is converted to CO2 and H2O.
• The energy stored in covalent bonds of pyruvate
is used to make ATP molecules.
7
Energy and Electrons from Glucose
• Fermentation does not involve O2. It is an
anaerobic process.
• Pyruvate is converted into lactic acid or ethanol.
• Breakdown of glucose is incomplete; less energy
is released than by cellular respiration.
7
Energy and Electrons from Glucose
• Redox reactions transfer the energy of electrons.
• A gain of one or more electrons or hydrogen
atoms is called reduction.
• The loss of one or more electrons or hydrogen
atoms is called oxidation.
• Whenever one material is reduced, another is
oxidized.
Figure 7.2 Oxidation and Reduction Are Coupled
7
Energy and Electrons from Glucose
• An oxidizing agent accepts an electron or a
hydrogen atom.
• A reducing agent donates an electron or a
hydrogen atom.
• During the metabolism of glucose, glucose is the
reducing agent (and is oxidized), while oxygen is
the oxidizing agent (and is reduced).
7
Energy and Electrons from Glucose
• The coenzyme NAD is an essential electron
carrier in cellular redox reactions.
• NAD exists in an oxidized form, NAD+, and a
reduced form, NADH + H+.
• The reduction reaction requires an input of
energy:
 NAD+ + 2H  NADH + H+
• The oxidation reaction is exergonic:
 NADH + H+ + ½ O2  NAD+ + H2O
Figure 7.3 NAD Is an Energy Carrier
Figure 7.4 Oxidized and Reduced Forms of NAD
7
Energy and Electrons from Glucose
• The energy-harvesting processes in cells use
different combinations of metabolic pathways.
• With O2 present, four major pathways operate:
 Glycolysis
 Pyruvate oxidation
 The citric acid cycle
 The respiratory chain (electron transport
chain)
• When no O2 is available, glycolysis is followed by
fermentation.
Table 7.1 Cellular Locations for Energy Pathways in Eukaryotes and Prokaryotes
7
Glycolysis: From Glucose to Pyruvate
• Glycolysis can be divided into two stages:
 Energy-investing reactions that use ATP
 Energy-harvesting reactions that produce ATP
7
Glycolysis: From Glucose to Pyruvate
• The energy-investing reactions of glycolysis:
 In separate reactions, two ATP molecules are used
to make modifications to glucose.
 Phosphates from each ATP are added to the
carbon 6 and carbon 1 of the glucose molecule to
form fructose 1,6-bisphosphate.
 The enzyme aldolase splits the molecule into two
3-C molecules that become glyceraldehyde 3phosphate (G3P).
Figure 7.6 Glycolysis Converts Glucose to Pyruvate (Part1)
Figure 7.6 Glycolysis Converts Glucose to Pyruvate (Part2)
7
Glycolysis: From Glucose to Pyruvate
• The energy-harvesting reactions of glycolysis:
 The first reaction (an oxidation) releases free
energy that is used to make two molecules of
NADH + H+, one for each of the two G3P
molecules.
 Two other reactions each yield one ATP per
G3P molecule. This part of the pathway is
called substrate-level phosphorylation.
 The final product is two 3-carbon molecules of
pyruvate.
Figure 7.6 Glycolysis Converts Glucose to Pyruvate (Part3)
Figure 7.6 Glycolysis Converts Glucose to Pyruvate (Part 4)
Figure 7.7 Changes in Free Energy During Glycolysis
7
Pyruvate Oxidation
• Pyruvate is oxidized to acetate which is converted
to acetyl CoA.
• Pyruvate oxidation is a multistep reaction
catalyzed by an enzyme complex attached to the
inner mitochondrial membrane.
• The acetyl group is added to coenzyme A to form
acetyl CoA. One NADH + H+ is generated during
this reaction.
Figure 7.8 Pyruvate Oxidation and the Citric Acid Cycle (Part 1)
7
The Citric Acid Cycle
• The citric acid cycle begins when the two carbons
from the acetate are added to oxaloacetate, a 4-C
molecule, to generate citrate, a 6-C molecule.
• A series of reactions oxidize two carbons from the
citrate. With molecular rearrangements, oxaloacetate
is formed, which can be used for the next cycle.
• For each turn of the cycle, three molecules of NADH
+ H+, one molecule of ATP, one molecule of FADH2,
and two molecules of CO2 are generated.
Figure 7.8 Pyruvate Oxidation and the Citric Acid Cycle (Part 2)
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• The respiratory chain uses the reducing agents
generated by pyruvate oxidation and the citric
acid cycle.
• The flow of electrons in a series of redox
reactions causes the active transport of protons
across the inner mitochondrial membrane,
creating a proton concentration gradient.
• The protons then diffuse through proton channels
down the concentration and electrical gradient
back into the matrix of the mitochondria, creating
ATP in the process.
• ATP synthesis by electron transport is called
oxidative phosphorylation.
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• The respiratory chain consists of four large protein
complexes bound to the inner mitochondrial
membrane, plus cytochrome c and ubiquinone
(Q).
Figure 7.10 The Oxidation of NADH + H+
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• NADH + H+ passes its hydrogen atoms to the
NADH-Q reductase protein complex.
• The NADH-Q reductase passes the hydrogens
on to ubiquinone (Q), forming QH2.
• The QH2 passes electrons to cytochrome c
reductase complex which in turn passes them to
cytochrome c.
• Next to receive them is cytochrome c oxidase
complex. Then they are passed to O2.
• Reduced oxygen unites with two hydrogen ions to
form water.
Figure 7.11 The Complete Respiratory Chain
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• As electrons pass through the respiratory chain,
protons are pumped by active transport into the
intermembrane space against their concentration
gradient.
• This transport results in a difference in electric
charge across the membrane.
• The potential energy generated is called the
proton-motive force.
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• Chemiosmosis is the coupling of the protonmotive force and ATP synthesis.
• NADH + H+ or FADH2 yield energy upon
oxidation.
• The energy is used to pump protons into the
intermembrane space, contributing to the protonmotive force.
• The potential energy from the proton-motive force
is harnessed by ATP synthase to synthesize ATP
from ADP.
Figure 7.12 A Chemiosmotic Mechanism Produces ATP (Part 1)
Figure 7.12 A Chemiosmotic Mechanism Produces ATP (Part 2)
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• Synthesis of ATP from ADP is reversible.
• The synthesized ATP is transported out of the
mitochondrial matrix as quickly as it is made.
• The proton gradient is maintained by the pumping
of the electron transport chain.
7
The Respiratory Chain:
Electrons, Protons, and ATP Production
• Two key experiments demonstrated that:
 A proton gradient across a membrane can
drive ATP synthesis.
 The enzyme ATP synthase is the catalyst for
this reaction.
Figure 7.13 Two Experiments Demonstrate the Chemiosmotic Mechanism
7
Fermentation: ATP from Glucose, without O2
• When there is an insufficient supply of O2, a cell
cannot reoxidize cytochrome c.
• Then QH2 cannot be oxidized back to Q, and
soon all the Q is reduced.
• This continues until the entire respiratory chain is
reduced.
• NAD+ and FAD are not generated from their
reduced form.
• Pyruvate oxidation stops, due to a lack of NAD+.
• Likewise, the citric acid cycle stops, and if the cell
has no other way to obtain energy, it dies.
7
Fermentation: ATP from Glucose, without O2
• Some cells under anaerobic conditions continue
glycolysis and produce a limited amount of ATP if
fermentation regenerates the NAD+ to keep
glycolysis going.
• Fermentation uses NADH + H+ to reduce
pyruvate, and consequently NAD+ is regenerated.
7
Fermentation: ATP from Glucose, without O2
• Some organisms are confined to anaerobic
environments and use only fermentation.
 These organisms lack the molecular
machinery for oxidative phosphorylation.
 They also lack enzymes to detoxify the toxic
by-products of O2, such as H2O2.
7
Fermentation: ATP from Glucose, without O2
• In lactic acid fermentation, an enzyme, lactate
dehydrogenase, uses the reducing power of
NADH + H+ to convert pyruvate into lactate.
• NAD+ is replenished in the process.
• Lactic acid fermentation occurs in some
microorganisms and in muscle cells when they
are starved for oxygen.
Figure 7.14 Lactic Acid Fermentation
7
Fermentation: ATP from Glucose, without O2
• Alcoholic fermentation involves the use of two
enzymes to metabolize pyruvate.
• First CO2 is removed from pyruvate, producing
acetaldehyde.
• Then acetaldehyde is reduced by NADH + H+,
producing NAD+ and ethanol.
Figure 7.15 Alcoholic Fermentation
7
Contrasting Energy Yields
• A total of 36 ATP molecules can be generated from
each glucose molecule in glycolysis and cellular
respiration.
• Each NADH + H+ generates 3 ATP molecules, and
each FADH2 generates 2 ATP by the chemiosmotic
mechanism.
• Fermentation has a net yield of 2 ATP molecules from
each glucose molecule.
• The end products of fermentation contain much more
unused energy than the end products of aerobic
respiration.
Figure 7.16 Cellular Respiration Yields More Energy Than Glycolysis Does (Part 1)
Figure 7.16 Cellular Respiration Yields More Energy Than Glycolysis Does (Part 2)
7
Relationships between Metabolic Pathways
• Glucose utilization pathways can yield more than
just energy. They are interchanges for diverse
biochemical traffic.
• Intermediate chemicals are generated that are
substrates for the synthesis of lipids, amino acids,
nucleic acids, and other biological molecules.
Figure 7.17 Relationships Among the Major Metabolic Pathways of the Cell
7
Relationships between Metabolic Pathways
• Catabolic interconversions:
 Polysaccharides are hydrolyzed into glucose,
which passes on to glycolysis.
 Lipids are converted to fatty acids, which
become acetate (then acetyl CoA), and
glycerol, which is converted to an intermediate
in glycolysis.
 Proteins are hydrolyzed into amino acids,
which feed into glycolysis or the citric acid
cycle.
7
Relationships between Metabolic Pathways
• Anabolic interconversions:
 Gluconeogenesis is the process by which
intermediates of glycolysis and the citric acid
cycle are used to form glucose.
 Acetyl CoA can form fatty acids.
 Intermediates can form amino acids.
 The citric acid cycle intermediate aketoglutarate is the starting point for the
synthesis of purines. Oxaloacetate is a starting
point for pyrimidines.
7
Relationships between Metabolic Pathways
• The levels of the products and substrates of
energy metabolism are remarkably constant.
• Cells regulate the enzymes of catabolism and
anabolism to maintain a balance, or metabolic
homeostasis.
7
Relationships between Metabolic Pathways
• What happens if inadequate food molecules are
available?
 Glycogen stores in muscle and liver are used
first.
 Fats are used next. But the brain can only use
glucose, so it must be synthesized by
gluconeogenesis which uses mostly amino
acids.
 Therefore, proteins must be broken down.
 After fats are depleted, proteins alone provide
energy.
7
Regulating Energy Pathways
• Metabolic pathways work together to provide cell
homeostasis.
• Positive and negative feedback control whether a
molecule of glucose is used in anabolic or
catabolic pathways.
Figure 7.19 Regulation by Negative and Positive Feedback
7
Regulating Energy Pathways
• The amount and balance of products a cell has is
regulated by allosteric control of enzyme
activities.
• Control points use both positive and negative
feedback mechanisms.
• The main control point in glycolysis is the enzyme
phosphofructokinase.
• This enzyme is inhibited by ATP and activated by
ADP and AMP.
7
Regulating Energy Pathways
• The main control point of the citric acid cycle is
the enzyme isocitrate dehydrogenase which
converts isocitrate to a-ketoglutarate.
• NADH + H+ and ATP are inhibitors of this enzyme.
NAD+ and ADP are activators of it.
• Accumulation of isocitrate and citrate occurs, but
is limited by the inhibitory effects of high ATP and
NADH.
• Citrate acts as an additional inhibitor to slow the
fructose 6-phosphate reaction of glycolysis and
also switches acetyl CoA to the synthesis of fatty
acids.
Figure 7.20 Feedback Regulation of Glycolysis and the Citric Acid Cycle (Part 1)
Figure 7.20 Feedback Regulation of Glycolysis and the Citric Acid Cycle (Part 2)