Cellular Respiration

Cellular respiration: a metabolic pathway that through a series of small steps, rearranges the atoms in the food molecules, making their stored energy available to the cell

  • Electrons are removed from food molecules, transferred to NADH and then to oxygen (diatomic molecule)

  • By end of process, energy from food has been transferred to ATP

  • cells completely rearrange food molecules into waste products (carbon dioxide and water)

-glucose is used as starting point to study the pathway

-energy release is a gradual process so the cell doesn’t get overwhelmed

-enzymes lower activation energy needed

Transferring energy to ATP

  • cellular respiration is exergonic

  • chemical potential energy slowly siphons off as atoms in glucose and oxygen rearrange

Moving electrons to oxygen

  • glucose is oxidized, oxygen reduced

  • electrons are moved as parts of hydrogen atoms—glucose into carbon dioxide, need to remove hydrogen atoms

    • oxygen into water means adding hydrogen atoms

Steps being taken

  • glycolysis is first part of cellular respiration, oxidation of glucose begins. some electrons transferred to NAD+. Glycolysis converts single glucose molecule, which contains six carbon atoms, into two molecules of pyruvate, each of which has three carbons—occurs in cytoplasm

  • The Krebs Cycle (also called the tricarboxylic acid cycle, TCA cycle, or citric acid cycle) continues the oxidation of the intermediates made from glucose, resulting in production of CO2. Transfers electrons to NAD+ and to another electron carrier, flavin adenine dinucleotide (FAD), which also helps in the subsequent stages of respiration to generate ATP, a key energy currency of the cell. Occurs in mitochondrion

  • Oxidative phosphorylation transfers electrons from electron carriers to an electron transport chain. Electron transport chain is a system of proteins in a membrane that help in the process that cells use to transfer energy to ATP. The final redox reaction is the transfer of electrons to oxygen, which is reduced to water. Oxidative phosphorylation occurs in the mitochondrion of the cell.

Glycolysis

  1. bonds between the atoms in the glucose break and reform between new combinations of atoms, creating two molecules of pyruvate (glycolysis breaks glucose in half)

  2. enzymes transfer energy from intermediates to ATP—transferring energy from ATP to the intermediates, representing energy investment phase of glycolysis, which is crucial for the eventual production of ATP in cellular respiration. Enzymes transfer more energy, representing energy payoff phase —for every break down glucose molecule, make four ATP, use two, net gain two molecules of ATP

  3. enzymes oxidize glucose and reduce NAD+—enzymes transfer electrons that were originally in glucose from an intermediate to NAD+, reducing the electron carrier to NADH+H+

Ten Steps of Glycolysis

  1. Enzyme transfers a phosphate from ATP to glucose, creating intermediate glucose-6-phosphate and releasing ADP as waste

  2. An enzyme rearranges the bonds in glucose-6-phosphate, creating intermediate fructose-6-phosphate

  3. an enzyme transfers a phosphate from ATP to fructose-6-phosphate, creating intermediate fructsose-1, 6-biphosphate and releasing ADP as waste

  4. Enzyme catalyzes the splitting of fructose 1, 6-bisphosphate into two 3-carbon molecules, dihydroxyacetone phosphate and glyceradehydes-3 phosphate

  5. An enzyme rearranges the bonds in dihydroxyacetone phosphate, converting it to glyceraldehyde-3-phosphate, so that it can proceed through the rest of glycolysis

  6. Electrons are transferred from glyceraldehyde-3-phosphate to NAD+, resulting in the formation of NADH + H+; at the same time, an inorganic phosphate group that was available in the cell is transferred to glyceraldehydes-3-phosphate, resulting in the formation of the intermediate 1, 3-biphosphoglycerate

  7. An enzyme transfers a phosphate group from the 1, 3- biphosphoglycerates to ADP, producing ATP and a new intermediate, 3-phosphoglcerate

  8. An enzyme rearranges the bonds in 3-phosphoglycerates, creating 2-phosphoglycerates

  9. AN enzyme catalyzes the removal of water from 2-phosphoglycerates, forming the intermediate phosphoenolpyruvate

  10. Another energy transfer occurs as phosphate group is transferred from phosphoenolpyruvate to ADP, producing ATP


*******the glucose-6-phosphate means that the phosphate is attached to number 6 carbon (farthest from carbonyl group, and 1-3 biphosphoglycerates means the two phosphates are attached to carbon 1 and 3—same pattern with all

Making ATP by substrate level phosphorylation

  • during steps 7 and 10 of glycolysis, phosphate group is transferred from an intermediate to ADP, forming energy carrier ATP

  • during both of these, the enzyme binds the intermediate and ADP in its active site and transfers phosphate from intermediate to ATP

    • called substrate level phosphorylation


Fermentation

  • lactic acid fermentation: cells that use this as their primary catabolic pathway do glycolysis, producing 2 pyruvate, 2 NADH + H+ and 2 ATP. Enzymes (lactate dehydrogenase) transfer electrons from NADH back to pyruvate, causing it to become lactic acid, and recycling NAD+ so that glycolysis can continue to occur and produce more ATP under anaerobic conditions.

    • cells use this when they lack ATP for work

      • people use lactic acid bacteria such as Lactobacillus in the preparation of food such as yogurt

      • when humans work out intensely

  • alcohol fermentation : yeasts use this kind of fermentation during production of bread, beer, and wine. 2 pyruvate, 2 NADH + H+, and 2 ATP. Decarboxylation removes carbon atom and two oxygen atoms from pyruvate, releasing as CO2 (causes bread to rise). Converts into new molecule, acetaldehyde. Transfer electrons from NADH to acetaldehyde, changing it into ethanol and recycling the NADH back to NAD+ so that glycolysis can proceed again. Ethanol is waste product.


The Krebs Cycle

  • occurs in mitochondrion

→ Enzymes oxidize intermediates and reduce electron carriers. Oxidation of intermediates = real work of the Krebs cycle. Redox reactions happen transfer electrons from intermediates to NAD+ and FAD. Exergonic. Reduced carriers transfer the energy and electrons to the electron transport chain, helping to make ATP

→enzymes can break bonds and rearrange atoms in the intermediates, removing carbon and oxygen atoms and releasing them as CO2. Decarboxylation happens three times for every molecule of pyruvate that leaves glycolysis and enters the Krebs cycle. Because glycolysis produces two 3-carbon molecules from glucose, the Krebs cycle occurs twice for every molecule of glucose that enters cellular respiration. Two rounds of Krebs cycle produces six molecules of carbon dioxide. Decarboxylation just prior to and during the Krebs cycle releases all six of the carbon atoms that were originally part of the glucose molecule. Last steps rearranges the atoms in the intermediate malate to recreate intermediate oxaloacetate, which is needed for the cycle to repeat itself again

→ Enzymes transfer energy to ATP. Most of the available energy in the intermediates is transferred directly to ATP by substrate level phosphorylation. Because Krebs cycle occurs twice for every molecule that goes through cellular respiration, a total of two ATP per glucose are made during Krebs

Linking Glycolysis and Krebs

  • The Krebs cycle officially begins when a two carbon molecule, acetyl-CoA is joined with a four carbon molecule, oxaloacetate, to form a 6-carbon molecule, citrate.

    • Pyruvate → acetyl CoA forms through a series of reactions—called different names. Pyruvate oxidation

      • Enzymes rearrange the atoms in pyruvate, removing carbon and oxygen, then releasing them as CO2. This decarboxylation reduces number of carbon atoms in the intermediate from 3 to 2

      • Enzymes oxidize pyruvate and then transfer electrons to NAD+, forming NADH in the process, which carries energy to the electron transport chain for ATP production.

      • enzymes add coenzyme A to an intermediate, forming acetyl-coA. Coenzyme A will be released from acetyl-coA as it enters the Krebs cycle

*to start Krebs cycle, so for pyruvate to be oxidated, it has to pass through two membranes of the mitochondria—-outer membrane easy to cross because of proteins called porins which allow small molecules to get through—inner membrane more difficult so special transport proteins are needed

Steps of the Krebs Cycle

  1. Enzymes join the 2-carbon molecule acetyl CoA with the four carbon molecule oxaloacetate, creating the 6-carbon molecule citrate. Water molecule added to the intermediate and co enzyme A is released back into the cell

  2. An enzyme rearranges the bonds in citrate, creating the molecule isocitrate. The number of carbon atoms doesn’t change.

  3. Enzymes oxidize and decarboxylate isocitrate, converting it to the 5-carbon molecule (alpha)-ketoglutarate. Enzymes transfer the electrons removed from isocitrate to the electron carrier NAD+, reducing it to NADH+H+. Enzymes release the carbon removed from isocitrate as Co2.

  4. Enzymes oxidize and decarboxylate alpha-ketoglutarate, converting it to the four carbon molecule succinyl-CoA. Enzymes transfer the electrons from alpha-ketoglutarate to the electron carrier NAD+, reducing it to NADH+H. Enzymes release the carbon removed from alpha-ketoglutarate as carbon dioxide Enzymes need help of coenzyme A during these reactions and add it to the intermediate

  5. Enzymes remove coenzyme A from succinyl CoA and release it back to the cell, changing succinyl-CoA into succinate This reaction is exergonic, allows phosphorylation of ADP by substrate level phosphorylation, producing ATP. Substrate level phosphorylation during Krebs cycle may produce ATP or it may produce similar energy carrier guanine triphosphate (GTP) Two different enzymes can catalyze substrate level phosphorylation during Krebs cycle, and each on prefers ADP or GDP in its active site The two enzymes that can catalyze substrate level phosphorylation during the Krebs cycle are: - **Succinate thiokinase** (also known as succinyl-CoA synthetase), which prefers to use GDP as a substrate. - **Phosphate-dependent phosphofructokinase**, which prefers to use ADP as a substrate.

  6. Succinate is oxidized, converting to fumarate. The electrons removed from succinate are transferred to the electron carrier FAD, which is reduced to FADH2. FAD/FADH2 have a similar structure to NAD/NADH and perform similar functions as electrons in the cells. In this reaction, FAD works better with the enzyme that catalyzes it.

  7. An enzyme catalyzes the addition of a water molecule to fumarate, converting it to malate

  8. Malate is oxidized, converting it to oxaloacetate. The electrons removed from malate are transferred to NAD+, which is reduced to NADH+H


*cells that have the enzymes to follow with the Krebs cycle are more efficient at extracting energy than cells that use glycolysis


Chemiosmosis and Oxidative Phosphorylation

Chemiosmotic theory of oxidative phosphorylation: explains how energy and electrons from food help make ATP

  • at end of glycolysis and Krebs cycle, not a lot of ATP is made—but a lot of reduced electron carriers have been made.

Electron Transport Chains

  • made of large proteins embedded in a membrane. Accept electrons and pass them from complex to complex. Some protein complexes use transfer energy from redox reactions and use it to do work like moving hydrogen ions across the membrane. Electron transport chain that is involved in cellular respiration is embedded in inner mitochondria membrane.

  • Important partner: ATP synthase enzyme, which synthesizes ATP. Most of ATP made in cellular respiration comes from process called chemiosmotic theory of oxidative phosphorylation, or just oxidative phosphorylation

    • ATP synthase is embedded in the mitochondrial membrane right along with the electron transport chain. One side of membrane is the intermembrane space; on the other side is the matrix of the mitochondrion. During oxidative phosphorylation, hydrogen ions enter a small channel in ATP synthase from the intermembrane space side of the membrane. Protons bind to ATP synthase and then exit the protein on the matrix side. Base of protein has binding sites for ADP and inorganic phosphate. The passage of every three protons provide enough energy for the synthesis of one ATP molecule

Transferring Electrons

  • electrons move along chain because each member is more electronegative than the previous one

  • oxygen is last one in eukaryotic cells, when accepts electrons it also picks up some protons and becomes H2O —why water is waste product of cellular respiration

Transferring energy from food to ATP

  1. Enzymes in glycolysis and Krebs transfer electrons from intermediates to electron carriers, increasing potential energy of the carriers as they are reduced. NADH and FADH2 are now carrying energy from the food

  2. Reduced electron carriers transfer energy along with the electrons they donate to the electron transport chain. Energy is now stored in the first protein complex of the chain

  3. As the complexes in the electron transport chain pass electrons along, they’re also passing some energy. Some complexes actively transport hydrogen ions across the membrane—concentrated protons are source of potential energy that can do work. Proton motive force now stores energy from the food

  4. The protein ATP synthase allows hydrogen ions to move back across the membrane. As hydrogen ions move, they cause ATP synthase to rotate, which increases energy in ATP synthase. Use this energy to form ATP


Steps of chemiosmotic theory of oxidative phosphorylation

  1. NADH donates electrons and energy to the electron transport chain. The first protein complex is reduced, while NADH is oxidized to NAD+

  2. Electrons move through the electron transport chain in a series of redox reactions, until they’re picked up by oxygen (O2), the final electron acceptor. Oxygen reduced to water

  3. Protein complexes I, II, and III use energy from the redox reactions to pump hydrogen ions across the membrane (potential energy of proton motive force)

  4. ATP synthase allows protons to recross the inner mitochondrial membrane. As the protons pass through the protein, it uses the energy to make ATP


How much ATP is made?

  • Every time a pair of electrons from NADH passes through the electron transport chain, enough energy for 3 ATP molecules

  • FADH2 electrons = 2 ATP molecules

  • in eukaryotes, NADH produced in the cytoplasm has to cross mitochondrion—can require energy in equivalence to one ATP molecule

  • In total, 36-38 produced


Breaking down carbs, proteins, and fat

Complex Carbs

  • Simple sugars, like glucose, fit right in or require few reactions to convert them into an intermediate in glycolysis

  • Body can easily feed complex carbohydrates into cellular respiration. Starch is polymer of glucose, so once the enzyme amylase breaks the chain down into individual glucose molecules, the glucose molecules fit right into glycolysis

  • Enzymes break down complex carbohydrates other than starch into individual sugar components.

Burning Fat

  • glycerol is a 3-carbon compound. An enzyme converts it to glyceraldehyde-3-phosphate, an intermediate in glycolysis

  • Enzymes break fatty acids into fragments containing 2 carbons each. Then, break 2-carbon fragments into acetyl-CoA

Proteins

  • amino acids have nitrogen-containing amino groups. Must be removed by deamination

  • after, enzymes convert the remaining part of the amino acid into an intermediate in glycolysis or Krebs—20 different amino acids enter at different points, largely dependent on number of carbon atoms


It’s a Two -Way Street: Connections between Metabolic Pathways

  • anabolism and catabolism—cellular respiration produces many intermediates that can be used for other metabolic pathways—building something for example

  • enzymes regulated through feedback inhibition

  • ATP is inhibitor, inhibits:

    • Phosphofructokinase, which catalyzes first step in glycolysis

    • Pyruvate dehydrogenase, which catalyzes the oxidation of pyruvate into acetyl-CoA

    • Citrate synthase, which catalyzes the synthesis of citrate from oxaloacetate and acetyl-CoA

  • also is cell has enough NADH

Packing on the fat

  • When ATP is not being used—ATP inhibits more from being made and binds to enzymes in fat-synthesis pathways to cause the process to speed up.

    • enzymes use glceraldehyde-3-phosphate from glycolysis to produce glycerol

    • enzymes use many molecules of acetyl-CoA to synthesize fatty acids

Building muscle

  • adult humans can synthesize 11 out of the 20 amino acids—enzymes synthesize most amino acids from the intermediates in the Krebs cycle