NOTES FOR BIOLOGY 1201

Section 001

Spring 2005

DR. STEVEN POMARICO

Energy flows through ecosystems while the chemicals within an ecosystem are recycled

Energy flow: Light => organic molecules => ATP + heat

Respiration: An Overview - 4.1.3

>>>>>Cellular respiration and fermentation are catabolic pathways

---Fermentation

         -no ATP production

         -organic electron donors and acceptors

---Cellular respiration

         -catabolism of organic molecules

         -ATP production

         -inorganic electron acceptor

C₆H₁₂O₆ + 6 O₂ => 6 CO₂ + 6 H₂O + Energy (ATP + heat)

How much energy??

                             ΔG= -686 kcal/mol of sugar.

>>>>>The ATP generated is used for work and then regenerated

Redox: A Brief Review - 4.1.4

>>>>>Redox reactions release energy when electrons move closer to electronegative atoms.

---Redox reactions (a.k.a. Oxidation-reduction reactions)

---Oxidation

---Reduction

Generalized redox reaction

                                       Xe^- + Y => X + Ye^-

         Xe^- is oxidized to X and Y is reduced to Ye^-

         X is the reducing agent, and Y is the oxidizing agent

The transfer of electrons doesn’t have to be a complete transfer (shown above) it may only be a partial transfer (e.g., combustion of methane)

>Cellular respiration as a redox reaction

       C₆H₁₂O₆ + 6 O₂ => 6 CO₂ + 6 H₂O

Carbon and hydrogen of C₆H₁₂O₆ is oxidized to 6 CO₂ and 6 H₂O, oxygen of 6 O₂ is reduced to 6 H₂O

The valence electrons of carbon and hydrogen lose potential energy as they shift toward the more electronegative oxygen atoms; the released energy is used to make ATP

Cellular fuels (e.g., carbohydrates and fats) are rich in C-H bonds

Coenzymes: The Role of NAD⁺ - 4.1.6

>>>>>The redox “fall” of electrons in cellular respiration is stepwise and uses (NAD⁺) Nicotinamide adenine dinucleotide

Electrons removed from glucose during cellular respiration are not transferred directly to oxygen, but are first passed to a special electron receptor NAD⁺

---NAD⁺

---coenzyme

    R                                 R

     |               dehydrogenase     |

H-C-OH + NAD⁺  =======>          C=O + NADH + H⁺

     |                                                 |

    R’                                        R’

NAD⁺ is reduced to NADH, and CHRR’OH is oxidized to CRR’O

NAD⁺ has only slightly greater affinity for electrons than other organic molecules.

>>>>>Cellular respiration is a cumulative function of glycolysis, the Krebs cycle, and electron transport.

Three metabolic stages of cellular respiration

         1. Glycolysis

         2. Krebs cycle

         3. Electron transport chain and oxidative phosphorylation

>>>>>Glycolysis harvests chemical energy by oxidizing glucose to pyruvate

---Glycolysis

         -A multi-step pathway that takes place in the cytoplasm.

         -Partially oxidizes glucose (C6) in two pyruvate (C3) molecules.

         -Occurs with or without O₂

The reactions of glycolysis occur in two phases

Glycolysis: The Initial Steps: Energy Input - 4.2.1

         1. Energy-investment phase

                   -uses cellular ATP to phosphorylate glycolysis intermediates

                   -costs two ATP molecules per glucose

Glycolysis: The Energy Payoff - 4.2.2

         2. Energy-yielding phase

                   -produces ATP by substrate-level phosphorylation

                   -yields 4 ATP molecules per glucose

                   -reduces 2 molecules of NAD⁺ to NADH per glucose

---substrate-level phosphorylation

The summary equation for glycolysis

C₆H₁₂O₆ + 2 NAD⁺ + 2 ADP + 2 P_i =>

               2 C₃H₄O₃ + 2 NADH + 2 H⁺ + 2 ATP + 2 H₂O

>>>>>The Krebs cycle completes the energy-yielding oxidation of organic molecules.

The Krebs cycle also goes by two other names:

                                       The Citric Acid Cycle

                                       The TCA (tricarboxylic acid) Cycle

Aerobic Respiration: The Acetyl CoA Step - 4.3.1

The reaction that connects glycolysis to the Krebs cycle (the bridge reaction) is the oxidation of pyruvate to acetyl CoA.

         This is a three-step process:

                   1. Removal of CO₂

                   2. Reduction of NAD⁺ to NADH. Two molecules of NADH per glucose                                     molecule.

                   3. Attachment of coenzyme A (a.k.a. CoA) to form acetyl CoA.

Aerobic Respiration: The Krebs Cycle - 4.3.2

---The Krebs cycle

         -Name after Hans Krebs, the main scientist involved in elucidating this

                   metabolic pathway.

         -8 steps

         -occurs in the mitochondrial matrix

         -two carbons enter from acetyl CoA, two different carbons leave as CO₂

         -coenzymes (NAD⁺ and FAD) are reduced:

                   Three NADH and one FADH₂ are produced for each turn of the cycle

         -one ATP is produced by substrate-level phosphorylation for each turn of the cycle

         -one of the starting (oxalacetate) materials is regenerated

         -two turns of the cycle per molecule of glucose entering glycolysis.

Summary equation for Krebs Cycle and the bridge reaction

C₃H₄O₃ + 4 NAD⁺ + ADP + P_i + FAD + 2 H₂0 =>

                      3 CO₂ + 4 NADH + 4 H⁺ + ATP + FADH₂

Remember that for every molecule of glucose entering glycolysis there are two pyruvate molecules that can enter the Krebs Cycle. Therefore two turns of the Krebs Cycle are needed to complete the oxidation of 1 glucose molecule.

Glycolysis and the Krebs Cycle - 4.3.3

Overall summary of Glycolysis and the Krebs Cycle combined.

C₆H₁₂O₆ + 10 NAD⁺ + 4 ADP + 4 P_i + 2 FAD + 2 H₂0 =>

              6 CO₂+ 10 NADH + 10 H⁺ + 4 ATP + 2 FADH₂

So where’s all the energy??

                             Stored in NADH and FADH₂.

>>>>>The electron transport chain of inner mitochondrial membrane couples electron transport to ATP synthesis.

The energy stored (as electrons) in NADH and FADH₂ is harvested when the energized electrons are transferred into the electron transport chain.

---electron transport chain

>>>>Electron transport chain and oxidative phosphorylation

         -The electron transport chain is located in the inner mitochondrial membrane

         -Accepts electrons from reduced coenzymes (NADH and FADH)

         -At every transfer in the electron transport chain the electrons are passed to a more

                   electronegative atom

         -At the end of the electron transport chain the electrons are passed to oxygen.

         -During the transfers of electrons in the electron transport chain energy is released.

         -The energy released during the transfer of electrons is used indirectly to

                   generate ATP via oxidative phosphorylation

         -Produces most (90%) of the ATP of cellular respiration.

---oxidative phosphorylation

The Electron Transport Chain - 4.4.1

>>>>>The pathway of electron transport

The electron transport chain is made of a series of electron carrier molecules embedded in the inner mitochondrial membrane.

---Cytochrome

Electrons from NADH enter the electron transport chain at the beginning at FMN.

Electrons from FADH₂ are added to the electron transport chain at a lower energy level at ubiquinone (Q).

The electrons are passed down the chain and finally to oxygen. As molecular oxygen is reduced (one atom picks up two electrons) it also picks up two protons to form a water molecule.

Oxidative Phosphorylation - 4.4.2

>>>>>Chemiosmosis: The energy-coupling mechanism.

The electron transport chain does not make ATP directly. Instead it generates a proton gradient across the inner mitochondrial membrane.

---Chemiosmosis

The inner mitochondrial membrane is the site of chemiosmotic ATP synthesis.

The electron transport chains is able to generates a proton gradient across the inner mitochondrial membrane because while some of the electron carriers of the chain move only electrons other carriers (which span the membrane) pick up a proton (from the matrix) when they accept the electrons and release the proton (to the intermembrane space) when they release the electron.

The result is:

         -The pH of the intermembrane space is 1-2 pH units lower than the matrix.

This proton gradient, and the potential energy it stores, is called a proton-motive force.

         This proton-motive force has to components:

                   1. Chemical gradient

                   2. Electrical gradient

Proton gradient

         Electrical gradient

                   SO WHERE IS ALL THE ATP??

For every NADH that feeds into the electron transport chain 3 protons are moved from the mitochondrial matrix to the outside of the inner membrane.

For every FADH₂ that feeds into the electron transport chain 2 protons are moved from the mitochondrial matrix to the outside of the inner membrane.

For every proton that crosses back into the mitochondrial matrix one ATP is synthesized by ATP synthase.

Note: That the description of the quantitation of ATP production (Section 4.4.3) is INCORRECT

Overall summary of Glycolysis, the Krebs Cycle and electron transport combined.

C₆H₁₂O₆ + 36 ADP + 36 P_i + 6 0₂ =>

                                                  6 CO₂ + 36 ATP + 42 H₂O

Remember where we started:

C₆H₁₂O₆ + 6 O₂ => 6 CO₂ + 6 H₂O

Anaerobic Respiration: The Fermentation of Pyruvate - 4.2.3

>>>>>Fermentation enables cell to produce ATP without using oxygen

Oxidation under anaerobic conditions

---Aerobic

---Anaerobic

---Fermentation

Glycolysis still converts glucose to pyruvate.

However, without oxygen the NADH reduced in glycolysis must be reoxidized.

To accomplish this reoxidation of NADH, the cell reduces the pyruvate.

>Two types of fermentation

The two most common products of pyruvate reduction are either ethanol or lactic acid.

         1. Alcohol fermentation

                    pyruvate loses a CO₂ and is then reduced to ethanol.

         2. Lactic acid fermentation

                   pyruvate is reduced to lactic acid.

>>>>>Comparison of Fermentation and Respiration

Similarities

         -Glycolysis splits glucose, reduces NAD⁺, and produces 2 ATP’s

Differences

         -How NAD⁺ is regenerated

         -Final electron acceptor

         -Amount of energy harvested

         -Requirement for oxygen

Other Fuels in Respiration - 4.4.4

>>>>>Glycolysis and the Krebs cycle are at a metabolic crossroads

Cellular respiration can accept components from most of the major types of macromolecules found in food.

         -Carbohydrates

                   -most of the polysaccharide breakdown product can be converted to                              either glucose or fructose.

         -Fats

                   -Glycerol can enter glycolysis at the start of the energy-yielding step

                   -Fatty acids are oxidized (beta oxidation) to 2-carbon acetyl groups                              and enter at the Krebs cycle.

         -Proteins

                   -Proteins are hydrolyzed to amino acids, deaminated (the amino group                              is removed) and enter at pyruvate or later (bridge reactions or Krebs                              cycle)

>>>>>Feedback mechanisms and control of cellular respiration

Cells can switch of the pathways they don’t need by feedback inhibition.

The ratio of ATP/ADP ratio reflects the energy state of a cell.

         Energy high          =>     ATP/ADP high

         Energy low           =>     ATP/ADP low

Phosphofructokinase a key regulatory point in glycolysis

         -ATP slows the enzyme down but ATP is also a substrate

         -Citrate also slows the enzyme down.

         -ADP speed the enzyme up but ADP is also a product.