7 Announcements Chapter 6 On-line Quiz – Deadline Tonight Please use the correct email address: [email protected] and not [email protected] or a diverse

7 Announcements

• Chapter 6 On-line Quiz – Deadline Tonight Please use the correct email address: [email protected] and not [email protected] or a diverse assortment of other email addresses.

• Examination 1 – Next Week! Coverage: Chapters 1-8 and syllabus Recall that the essay will be from Chapter 1. Sample exam on BIO 121 website

Fall Break: In two weeks!!!

7Cellular 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.


• Principles governing metabolic pathways:

Metabolic pathways are formed by complex chemical transformations which occur in separate reactions. [A to B to C to ….Z]

Each reaction in the pathway is catalyzed by a specific enzyme.

Metabolic pathways are similar in all organisms. [slugs, slime molds, & staph]

In eukaryotes, many metabolic pathways are compartmentalized in organelles.

The operation of each metabolic pathway can be regulated by the activities of key enzymes.


• 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.


• About one-third of the energy from glucose is collected in ATP.

G for the complete conversion of glucose is –686 kcal/mol. [Some steps are endergonic, however.]

• The overall set of reactions is therefore highly exergonic, and it drives the endergonic formation of ATP.


• Three metabolic processes are used in the breakdown of glucose for energy:

Glycolysis

Cellular Respiration

Fermentation

Figure 7.1 Energy for Life


• 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.

http://www.ebi.ac.uk/interpro/potm/2004_2/Page1_files/image006.gif


• 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.

http://ebiomedia.com/prod/images/PHOTRESP.JPG

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Graphics/MolStruct/Pyruvate.jpg


• 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.

http://www.mr-damon.com/experiments/2sp/projects/images/fermentation.jpg

7 Transfer of Energy

• We have already discussed the transfer of energy via a phosphate group (ATP = ADP + Pi).

• Another way that energy is transferred within living organisms is via electrons.


• Redox reactions (oxidation-reduction 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


• 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 Electrons or Hydrogen Atoms

• Redox reactions may also involve the transfer of hydrogen atoms (not ions) because a hydrogen atom has one electron (the H+ ion does not).

http://www.palladiumcoins.com/images/hydrogen.jpg

H = H+ + e-

proton electron

(H ion)


• The coenzyme NAD (nicotinamide adenine dinucleotide) 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

Becomes oxidized.

Becomes reduced.High

energy

Low energy

Compare with ATP and ADP cycle diagram.

Figure 7.4 Oxidized and Reduced Forms of NAD

NAD

Note the two nucleotides, hence “dinucleotide.”


• 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 Overview of Pathways

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

http://www.ebi.ac.uk/interpro/potm/2004_2/Page1_files/image006.gif

In cytosol.

Figure 7.6 Glycolysis Converts Glucose to Pyruvate (Part1)

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

Figure 7.8 Pyruvate Oxidation and the Citric Acid Cycle (Part 1)

Pyruvate oxidation is a multistep reaction catalyzed by an enzyme complex attached to the inner mitochondrial membrane.

In mitochondrion.


In matrix.

Acetyl CoA donates 2-C acetyl group to oxaloacetate.

7 Now What?

We know we can use the ATPs for all kinds of things.

What are we going to do with

NADH

FADH2

next time

7

7 Announcements & Concerns

•Where did the NADH and FADH2 go???


Pyruvate oxidation is a multistep reaction catalyzed by an enzyme complex attached to the inner mitochondrial membrane.

In mitochondrion.


In matrix.

Acetyl CoA donates 2-C acetyl group to oxaloacetate.

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.


• The respiratory chain consists of four large protein complexes bound to the inner mitochondrial membrane, plus cytochrome c and ubiquinone (Q).

http://faculty.ircc.edu/faculty/tfischer/images/mitochondrion.jpg

Figure 7.10 The Oxidation of NADH + H+


• NADH + H+ passes its hydrogen atoms to the NADH-Q reductase protein complex (I).

• The NADH-Q reductase passes the hydrogens on to ubiquinone (Q) (above II, which is succinate dehydrogenase), forming QH2.

• The QH2 passes electrons to cytochrome c reductase complex (III) which in turn passes them to cytochrome c.

• Next to receive them is cytochrome c oxidase complex (IV). Then they are passed to O2.

• Reduced oxygen unites with two hydrogen ions to form water.

Figure 7.11 The Complete Respiratory Chain

7 A Review

• Layered Figure 7-10 Oxidation of NADH + H+

7 Why?

“What’s the point of using all the NADH and FADH2 to make water?”

http://www.lionking.org/imgarchive/Act_2/SimbaConfused.jpg


• 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.


• Chemiosmosis is the coupling of the proton-motive 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 proton-motive force.

• The potential energy from the proton-motive force is harnessed by ATP synthase to synthesize ATP from ADP.

7 A Review

• Layered Figure 7-12 A Chemiosmotic Mechanism Produces ATP

Figure 7.12 A Chemiosmotic Mechanism Produces ATP (Part 1)

Figure 7.12 A Chemiosmotic Mechanism Produces ATP (Part 2)

7 Shutdown of cellular respiration, if without O2

• When there is an insufficient supply of O2, and therefore nothing to take away the electrons, 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, i.e., not reoxidized.

• 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

OTHER OPTIONS?

• Some cells under anaerobic conditions continue glycolysis and produce a limited amount of ATP if fermentation regenerates the NAD+ to keep glycolysis (not aerobic respiration) going.

• Fermentation uses NADH + H+ to reduce pyruvate, and consequently NAD+ is regenerated.


• 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.

http://www.mensfitnessmagazine.co.uk/images/library_UK_6/can_i_work_out_with_sore_muscles_3062_13.jpg

Figure 7.14 Lactic Acid Fermentation


• 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.

http://www.murphguide.com/images/pitcher-of-beer.gif

For those 21 and over…

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. [lactate: 3C; alcohol 2C]

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.

7 More to it than just Energy

• Layered Figure 7-17 Relationships among the major metabolic pathways of the cell.

Figure 7.17 Relationships Among the Major Metabolic Pathways of the Cell


• 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.


• 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 -

ketoglutarate is the starting point for the synthesis of purines. Oxaloacetate is a starting point for pyrimidines.

7 Regulating Energy Pathways

REGULATION!

• 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.

• 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, which catalyzes the reaction from fructose 6-phosphate to fructose 1,6 bisphosphate.

• This enzyme is inhibited by ATP [and citrate if citric acid cycle is refusing to proceed (isocitrate dehydrogenase)] and activated by ADP and AMP.

http://www.biocristalografia.df.ibilce.unesp.br/valmir/bioquimica/glicolise/phosphofructokinase.gif

7 Phosphofructokinase

• Inhibitors ATP Citrate

Lots around?

• Activators AMP ADP

http://www.schoolscience.co.uk/content/5/chemistry/proteins/images/p33fig13.gif


• 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)

Documents

7 Announcements Chapter 6 On-line Quiz – Deadline Tonight Please use the correct email address: [email protected] and not [email protected] or a diverse