Chapter 5 Study Guide: Cell Respiration and Metabolism

Metabolism

• Metabolism is all the reactions in the body that involve energy transformation.
• It is divided into two categories:
  • Catabolism: breaks down larger organic molecules and releases energy.
    • Is the primary source of energy for making ATP.
  • Anabolism: makes larger molecules and requires input of energy.
    • Includes the body’s large energy-storage molecules including glycogen, fat, and protein.
    • Aka: Endergonic reactions, non-spontaneous reaction

Energy Metabolism Using Blood Glucose

• Blood glucose may be obtained from food via the digestive tract or the liver, which may produce it from stored glycogen.
• Plasma glucose enters the cytoplasm of cells, where it can be stored for energy by either anaerobic metabolism or aerobic cell respiration.

Glycolysis

• Glycolysis: the breakdown of glucose (C6H{12}O_6) for energy begins with the metabolic pathway in the cytoplasm known as glycolysis that involves many enzymatically controlled steps.
• Glucose, a six-carbon (hexose) sugar, is converted into two molecules of pyruvate (half size of glucose).
  • Each pyruvate contains 3 carbons, 3 oxygens, and 4 hydrogens.
  • 2 pyruvates account for only 8 hydrogens; 4 hydrogens are removed from the intermediates in glycolysis.
  • Each pair of these hydrogen atoms is used to reduce a molecule of nicotinamide adenine dinucleotide (NAD). In this process, each pair of hydrogen atoms donates 2 electrons to NAD, thereby reducing it.
  • The reduced NAD binds 1 proton from the hydrogen atoms, leaving 1 proton unbound as H^+.
  • Starting from 1 glucose molecule, therefore, glycolysis results in the production of 2 molecules of NADH and 2H^+. The H^+ will follow the NADH in subsequent reactions, so for simplicity we can refer to reduced NAD simply as NADH.
  • Glycolysis is exergonic and a portion of the energy that is released is used to drive the endergonic reaction ADP + Pi \rightarrow ATP. At the end of the glycolytic pathway, there is a net gain of 2 ATP molecules per glucose molecule, as indicated in the overall equation for glycolysis: Glucose + 2 NAD +2 ADP +2 Pi \rightarrow 2 pyruvate + 2NADH + 2ATP (rearranging of H)
  • Glucose must be activated by 2 ATPs, a process called phosphorylation, before energy can be obtained.
  • In glycolysis, 2 ATP are added and 4 are produced for a net gain of 2 ATP and 2 NADH.
• Glycolysis steps:
  • 1: Glucose is phosphorylated to glucose 6-phosphate using ATP.
  • 2: G6P is converted into its isomer, fructose 6-phosphate.
  • 3-4: Notice that the six-carbon-long molecule is split into 2 separate three-carbon-long molecules.
  • 5: 2 pairs of hydrogens are removed and used to reduce NAD to 2 NADH + H^+; these reduced coenzymes are important products of glycolysis.
  • 6: A phosphate group is removed from each 1,3-biphosphoglyceric acid, forming 2 ATP and 2 molecules of 3-phosphoglyceric acid.
  • 7-8: Are isomerizations.
  • 9: The last phosphate group is removed for each intermediate; this forms 2 ATP (for a net gain of 2 ATP) and 2 molecules of pyruvate.

Lactate Pathway

• When oxygen is not available in sufficient amounts, the NADH+H^+ produced in glycolysis is oxidized in the cytoplasm by donating its electrons to pyruvate. This results in the re-formation of NAD and the addition of 2 hydrogen atoms to pyruvate, which is reduced. This addition of 2 hydrogen atoms to pyruvate produces lactate.
• Glucose converted into lactate is a type of anaerobic metabolism (no use of O_2).
• The lactate pathway yields a net gain of 2 ATP molecules (produced by glycolysis) per glucose molecule.
• Cells can survive without O_2 as long as they can produce sufficient energy for their needs in this way, as long as lactate concentrations do not become excessive. Some tissues are better adapted to aerobic conditions than others. Skeletal muscles survive longer than cardiac muscles, which would survive longer than the brain.

Gluconeogenesis & the Cori Cycle

• Gluconeogenesis is the metabolic pathway in which glucose is synthesized from non-carbohydrate precursors such as lactate, glycerol, and certain amino acids.
• Predominantly occurring in the liver (and to a lesser extent in the kidney cortex), it’s vital for maintaining blood glucose during fasting.
• Key enzymes bypass glycolysis’s irreversible steps: pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase.
• Requires ATP and GTP.
• The Cori cycle couples muscle and liver metabolism under anaerobic conditions:
  1. In exercising muscle, pyruvate → lactate via lactate dehydrogenase.
  2. Lactate travels through the blood to the liver.
  3. In the liver, lactate → pyruvate → glucose via gluconeogenesis.
  4. Glucose is then released into the bloodstream and taken back up by muscle.

Aerobic Respiration of Glucose: The Krebs Cycle

• In mitochondria, pyruvate (from glycolysis) is converted to acetyl-CoA by pyruvate dehydrogenase.
• Acetyl-CoA enters the Krebs cycle, undergoing:
  1. Condensation: acetyl-CoA + oxaloacetate → citrate.
  2. Isomerization/decarboxylations: citrate → isocitrate → α-ketoglutarate → succinyl-CoA, releasing CO_2 and reducing NAD→NADH.
  3. Conversion steps: succinyl-CoA → succinate (generating GTP), followed by succinate → fumarate → malate → oxaloacetate, generating FADH_2 and NADH.
• Each acetyl-CoA yields:
  • 2 CO_2
  • 3 NADH
  • 1 FADH_2
  • 1 GTP

Electron Transport Chain & Oxidative Phosphorylation

• Electron Transport Chain (ETC) is located in the inner mitochondrial membrane and consists of complexes I–IV plus mobile carriers (ubiquinone, cytochrome c):
  • NADH donates electrons to Complex I; FADH_2 to Complex II.
  • Electrons travel through complexes and carriers, ultimately reducing O_2 to water at Complex IV.
  • Complexes I, III, and IV pump protons into the intermembrane space, creating a proton gradient.
• Oxidative phosphorylation uses the proton-motive force to drive ATP synthesis via ATP synthase (Complex V).
• As protons flow back into the matrix through ATP synthase, ADP + Pi \rightarrow ATP.
• Oxygen’s role is essential—it accepts electrons at Complex IV and combines with protons to form water, maintaining electron flow and gradient integrity.

Hepatic Glucose Production

• From glycogen (glycogenolysis): Glycogen → glucose-1-phosphate → glucose-6-phosphate → free glucose (via glucose-6-phosphatase in the liver), released into circulation.
• From non-carbohydrate sources (gluconeogenesis):
  • Amino acids: glucogenic types feed in at pyruvate or TCA cycle intermediates.
  • Glycerol: from triglyceride breakdown → glycerol-3-phosphate → dihydroxyacetone phosphate → gluconeogenesis.
  • Lactate: via the Cori cycle.
• In the liver, glucose-6-phosphate → glucose (via glucose-6-phosphatase) → exported into blood.

Triglycerides & Ketone Bodies

• Triglycerides → Aerobic Respiration:
  • Lipases hydrolyze triglycerides into glycerol and fatty acids.
  • Glycerol converges into gluconeogenesis (→ DHAP).
  • Fatty acids undergo β-oxidation in mitochondria, generating acetyl-CoA, NADH, FADH_2 → enter Krebs + ETC → large ATP yield.
• Ketone bodies:
  • When acetyl-CoA accrual exceeds TCA capacity (e.g., starvation, diabetes), the liver converts it into ketone bodies: acetoacetate, β-hydroxybutyrate, and acetone.
  • These are water-soluble and exported to the brain and muscle for energy.
  • In peripheral tissues, acetoacetate and β-hydroxybutyrate reconvert to acetyl-CoA and enter the Krebs cycle.