Cellular Respiration

• Cellular respiration involves oxidizing biological fuels with an inorganic electron acceptor like oxygen.
• This drives the production of ATP (adenosine triphosphate), which stores energy.
• It's a metabolic process in cells that transfers chemical energy from nutrients to ATP and releases waste products.
• Cellular respiration occurs in plants and some bacteria.
• It can be aerobic (requires oxygen) or anaerobic.
• Some organisms can switch between aerobic and anaerobic respiration.
• Reactions are catabolic, breaking down large molecules into smaller ones.
• This process releases large amounts of ATP.
• It's a key way cells release chemical energy for cellular activity.
• The overall reaction involves biochemical steps, including redox reactions.
• It's technically a combustion reaction but with a slow, controlled energy release.
• Common nutrients used include sugar, amino acids, and fatty acids.
• Molecular oxygen (O2) is the most common oxidizing agent.
• The ATP's third phosphate group bond is broken to release energy for cellular processes.
• These processes include biosynthesis, locomotion, and molecule transport.

Aerobic Respiration

• Requires oxygen (O2) to create ATP.

• Carbohydrates, fats, and proteins are reactants.

• It's the preferred method of pyruvate production in glycolysis.

• Pyruvate must be transported to the mitochondria for oxidation via the citric acid cycle.

• Products are carbon dioxide, water, ATP (via substrate-level phosphorylation, NADH, and FADH2).

• Mass balance of the global reaction: C6H12O6 (s) + 6 O2 (g) → 6 CO2 (g) + 6 H2O (l) + energy

• ΔG = −2880 kJ per mol of C6H12O6, indicating an exothermic reaction.

• The potential of NADH and FADH2 is converted to ATP through an electron transport chain.

• Oxygen and protons (hydrogen ions) act as "terminal electron acceptors".

• Most ATP is produced by oxidative phosphorylation.

• Energy released creates a chemiosmotic potential by pumping protons across a membrane.

• This potential drives ATP synthase, producing ATP from ADP and a phosphate group.

• Biology textbooks often state that 38 ATP molecules can be made per oxidized glucose molecule.

• Current estimates range around 29 to 30 ATP per glucose due to losses from leaky membranes and the cost of moving pyruvate and ADP into the mitochondrial matrix.

• Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism.

• Some anaerobic organisms can continue anaerobic respiration, yielding more ATP.

• They use inorganic molecules other than oxygen as final electron acceptors.

• They share the glycolysis pathway, and aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation.

• Post-glycolytic reactions occur in the mitochondria in eukaryotic cells and in the cytoplasm in prokaryotic cells.

• Plant respiration accounts for about half of the CO2 generated annually by terrestrial ecosystems.

Glycolysis

• A metabolic pathway in the cytosol of cells in all living organisms.
• It can be translated as "sugar splitting".
• Occurs regardless of oxygen's presence.
• Converts one glucose molecule into two pyruvate molecules.
• Generates energy in the form of two net ATP molecules.
• Four ATP molecules are produced, but two are consumed in the preparatory phase.
• Initial phosphorylation of glucose increases reactivity, allowing cleavage into two pyruvate molecules by aldolase.
• During the pay-off phase, four phosphate groups are transferred to four ADP to make four ATP.
• Two NADH are also produced during the pay-off phase.
• The overall reaction is: Glucose + 2 NAD+ + 2 Pi + 2 ADP → 2 pyruvate + 2 NADH + 2 ATP + 2 H+ + 2 H2O + energy
• Starting with glucose, 1 ATP is used to donate a phosphate to glucose to produce glucose 6-phosphate.
• Glycogen can be converted into glucose 6-phosphate with the help of glycogen phosphorylase.
• During energy metabolism, glucose 6-phosphate becomes fructose 6-phosphate.
• An additional ATP is used to phosphorylate fructose 6-phosphate into fructose 1,6-bisphosphate with the help of phosphofructokinase.
• Fructose 1,6-biphosphate then splits into two phosphorylated molecules with three carbon chains which later degrades into pyruvate.

Oxidative Decarboxylation of Pyruvate

• Pyruvate is oxidized to acetyl-CoA and CO2 by the pyruvate dehydrogenase complex (PDC).
• The PDC contains multiple copies of three enzymes and is located in the mitochondria of eukaryotic cells and in the cytosol of prokaryotes.
• In the conversion of pyruvate to acetyl-CoA, one molecule of NADH and one molecule of CO2 is formed.

Citric Acid Cycle

• Also called the Krebs cycle or the tricarboxylic acid cycle.
• When oxygen is present, acetyl-CoA is produced from pyruvate molecules created from glycolysis.
• Once acetyl-CoA is formed, aerobic or anaerobic respiration can occur.
• When oxygen is present, the mitochondria will undergo aerobic respiration which leads to the Krebs cycle.
• If oxygen is not present, fermentation of the pyruvate molecule will occur.
• In the presence of oxygen, when acetyl-CoA is produced, the molecule then enters the citric acid cycle (Krebs cycle) inside the mitochondrial matrix, and is oxidized to CO2 while at the same time reducing NAD to NADH.
• NADH can be used by the electron transport chain to create further ATP as part of oxidative phosphorylation.
• To fully oxidize the equivalent of one glucose molecule, two acetyl-CoA must be metabolized by the Krebs cycle.
• Two low-energy waste products, H2O and CO2, are created during this cycle.
• The citric acid cycle is an 8-step process involving 18 different enzymes and co-enzymes.
• During the cycle, acetyl-CoA (2 carbons) + oxaloacetate (4 carbons) yields citrate (6 carbons).
• Citrate is rearranged to a more reactive form called isocitrate (6 carbons).
• Isocitrate is modified to become α-ketoglutarate (5 carbons), succinyl-CoA, succinate, fumarate, malate and, finally, oxaloacetate.
• The net gain from one cycle is 3 NADH and 1 FADH2 and 1 high-energy GTP.
• The total yield from 1 glucose molecule (2 pyruvate molecules) is 6 NADH, 2 FADH2, and 2 ATP.

Oxidative Phosphorylation

• In eukaryotes, it occurs in the mitochondrial cristae.
• It comprises the electron transport chain that establishes a proton gradient.
• ATP is synthesized by the ATP synthase enzyme when the chemiosmotic gradient is used to drive the phosphorylation of ADP.
• The electrons are finally transferred to exogenous oxygen, and water is formed.

Efficiency of ATP Production

• Theoretical yield of 38 ATP molecules per glucose during cellular respiration isn't typically reached because the cost of moving pyruvate, phosphate, and ADP.

• Pyruvate is taken up by a specific, low Km transporter to bring it into the mitochondrial matrix for oxidation by the pyruvate dehydrogenase complex.

• The phosphate carrier mediates the electroneutral exchange (antiport) of phosphate (H2PO4−; Pi) for OH− or symport of phosphate and protons (H+) across the inner membrane.

• The driving force for moving phosphate ions into the mitochondria is the proton motive force.

• The ATP-ADP translocase (also called adenine nucleotide translocase, ANT) is an antiporter and exchanges ADP and ATP across the inner membrane.

• The proton electrochemical gradient is reduced, meaning that more than 3 H+ are needed to make 1 ATP.

• Reduces the theoretical efficiency of the whole process and the likely maximum is closer to 28–30 ATP molecules.

• In practice the efficiency may be even lower because the inner membrane of the mitochondria is slightly leaky to protons.

• An uncoupling protein known as thermogenin is expressed in some cell types and is a channel that can transport protons.

• When this protein is active in the inner membrane it short circuits the coupling between the electron transport chain and ATP synthesis.

• The potential energy from the proton gradient is not used to make ATP but generates heat.

• ATP : NADH+H+ and ATP : FADH2 ratios during the oxidative phosphorylation appear to be not 3 and 2, but 2.5 and 1.5 respectively.

• ATP synthase produces 1 ATP / 3 H+.

• However the exchange of matrix ATP for cytosolic ADP and Pi (antiport with OH− or symport with H+) mediated by ATP–ADP translocase and phosphate carrier consumes 1 H+ / 1 ATP as a result of regeneration of the transmembrane potential changed during this transfer, so the net ratio is 1 ATP : 4 H+.

• The mitochondrial electron transport chain proton pump transfers across the inner membrane 10 H+ / 1 NADH+H+ (4 + 2 + 4) or 6 H+ / 1 FADH2 (2 + 4).

• Final stoichiometry: 1 NADH+H+ : 10 H+ : 10/4 ATP = 1 NADH+H+ : 2.5 ATP, 1 FADH2 : 6 H+ : 6/4 ATP = 1 FADH2 : 1.5 ATP

• ATP : NADH+H+ coming from glycolysis ratio during the oxidative phosphorylation is 1.5, as for FADH2, if hydrogen atoms (2H++2e−) are transferred from cytosolic NADH+H+ to mitochondrial FAD by the glycerol phosphate shuttle located in the inner mitochondrial membrane and 2.5 in case of malate-aspartate shuttle transferring hydrogen atoms from cytosolic NADH+H+ to mitochondrial NAD+

• Final figures per molecule of glucose: Substrate-level phosphorylation: 2 ATP from glycolysis + 2 ATP (directly GTP) from Krebs cycle and oxidative phosphorylation is 2 NADH+H+ from glycolysis: 2 × 1.5 ATP (if glycerol phosphate shuttle transfers hydrogen atoms) or 2 × 2.5 ATP (malate-aspartate shuttle), 2 NADH+H+ from the oxidative decarboxylation of pyruvate and 6 from Krebs cycle: 8 × 2.5 ATP,2 FADH2 from the Krebs cycle: 2 × 1.5 ATP for a total of 4 + 3 (or 5) + 20 + 3 = 30 (or 32) ATP

• The total ATP yield in ethanol or lactic acid fermentation is only 2 molecules coming from glycolysis, because pyruvate is not transferred to the mitochondrion and finally oxidized to the carbon dioxide (CO2), but reduced to ethanol or lactic acid in the cytoplasm.

Fermentation

• Without oxygen, pyruvate is not metabolized by cellular respiration.
• Pyruvate remains in the cytoplasm and undergoes fermentation.
• It's converted to waste products which may be removed from the cell.
• Fermentation oxidizes NADH to NAD+ that can be re-used in glycolysis preventing the buildup of NADH in the cytoplasm.
• The waste product varies depending on the organism.
• In skeletal muscles, the waste product is lactic acid. This is lactic acid fermentation.
• During strenuous exercise, when energy demands exceed energy supply, the respiratory chain cannot process all of the hydrogen atoms joined by NADH.
• NAD+ regenerates when pairs of hydrogen combine with pyruvate to form lactate, catalyzed by lactate dehydrogenase in a reversible reaction.
• Lactate can also be used as an indirect precursor for liver glycogen.
• During recovery, when oxygen becomes available, NAD+ attaches to hydrogen from lactate to form ATP.
• In yeast, the waste products are ethanol and carbon dioxide, called alcoholic or ethanol fermentation.
• ATP generated in this process is made by substrate-level phosphorylation, which does not require oxygen.
• Fermentation is less efficient at using the energy from glucose: only 2 ATP are produced per glucose.
• Glycolytic ATP is produced more quickly.
• Prokaryotes increase the rate of glycolytic reactions to continue a rapid growth rate when shifted from an aerobic environment to an anaerobic environment.
• Multicellular organisms use fermentation during short bursts of strenuous activity to supplement the ATP production

Anaerobic Respiration

• Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor to produce large amounts of energy and drive the bulk production of ATP.
• Microorganisms, either bacteria or archaea, use it in which neither oxygen (aerobic respiration) nor pyruvate derivatives (fermentation) is the final electron acceptor.
• An inorganic acceptor such as sulfate (SO2−4), nitrate (NO−3), or sulfur (S) is used.
• Such organisms could be found in unusual places such as underwater caves or near hydrothermal vents at the bottom of the ocean, as well as in anoxic soils or sediment in wetland ecosystems.
• In July 2019, a scientific study of Kidd Mine in Canada discovered sulfur-breathing organisms which live 7900 feet (2400 meters) below the surface
• These organisms also consume minerals such as pyrite as their food source.

Questions about the role of ATP, metabolic processes, and the relationship between catabolic reactions and cellular respiration. Includes the equation for cellular respiration, the role of oxygen and the process in the mitochondria.