Exam Notes on Metabolism

Digestion

• Pepsinogen:
  • Secreted by chief cells in the stomach.
  • Breaks down protein (peptide) bonds during digestion in the stomach.
• Chewing:
  • Breaks down food macroscopically but doesn't break down protein at a molecular level.
  • Molecular breakdown begins in the stomach.
• Digestion of Protein:
  • Starts in the stomach.
• Amylase:
  • Digests carbohydrates.
  • Digestion starts in the mouth
• Triglycerides:
  • Fats.
• Lipase:
  • Enzyme from the pancreas that digests fatty acids.
• Bile and Pancreatic Acid:
  • Join in the duodenum (small intestine).

Duodenum

• Neutralization:
  • Neutralizes stomach acid.
• Ampulla of Vater:
  • Location where the common bile duct and pancreatic duct join.

Bile

• Production:
  • Made in the liver.
• Gallbladder:
  • Stores bile; does not produce it.
  • Contracts to release bile upon sensing fatty foods.
  • Cholecystokinin (CCK) is the hormone that signals the gallbladder to contract.
• Liver Anatomy:
  • Two lobes joined by the falciform ligament.
  • Portal system with the inferior vena cava.
  • Highly vascularized.

Pancreas

• Functions:
  • Endocrine: Produces insulin that goes into the bloodstream (hormones).
  • Exocrine: Produces amylase and lipase, which go to the stomach.
• Other Endocrine Hormones:
  • Glucagon, somatostatin (not essential to know for the test).
• Exocrine Products:
  • Amylase and lipase enter the duodenum with bile.
• Bile Function:
  • Emulsifies fats (micelles).
• Amylase and Lipase Function:
  • Further digests fats and carbohydrates.

Gallstones (Cholelithiasis)

• Gallbladder Removal:
  • Bile no longer enters directly, affects fat digestion.
• Blockage at Ampulla of Vater:
  • If a gallstone blocks the ampulla of Vater, amylase and lipase back up into the pancreas.
  • Causes acute pancreatitis: the pancreas digests itself due to the backed-up enzymes.
  • Associated with high mortality.
  • Risk factors: obesity, fatty foods, smoking, diabetes, alcohol.
• Pancreatitis Pain:
  • Epigastric pain radiating to the back.

Energy Conversion

• ATP Production:
  • Food is converted to energy (ATP).
• Fatty Acids:
  • Come from triglycerides.
• Pyruvate:
  • Every sugar molecule can produce two pyruvate molecules, enabling two cycles of the citric acid cycle.

Citric Acid Cycle

• Nomenclature:
  • Also known as the Krebs cycle or the TCA (tricarboxylic acid) cycle.
  • All three names refer to the same process.
• Acetyl CoA:
  • Important product derived from pyruvate.
• Monosaccharide to Pyruvate:
  • Involves eight enzymatic steps (simplified on slides).
• Pyruvate to Acetyl CoA:
  • Involves enzymatic processes.
• Citric Acid Cycle Steps:
  • Involves six complex steps (succinate, isocitrate, fumarate, alpha-ketoglutarate, etc.).
• Key Point:
  • Acetyl CoA is oxidized to CO_2.
• CO_2 Importance:
  • Goes to the electron transport chain for further processing.

Glucose Breakdown

• Process:
  • Glucose → 2 Pyruvate → Acetyl CoA → Citric Acid Cycle → Electron Transport Chain
• Citric Acid Cycle (TCA/Krebs):
  • Operates in a counterclockwise direction.
  • Produces reactants essential for the electron transport chain.
  • Generates some ATP (approximately 4 ATP).
• Electron Transport Chain:
  • Generates the majority of ATP (approximately 32 ATP).
  • Reactants from the citric acid cycle drive the electron transport chain.
• Reactants:
  • O_2, NADH, and FADH.
• ATP Investment:
  • The body uses ATP to produce more ATP.

Electron Transport Chain and Oxidative Phosphorylation

• Role of CO_2:
  • Drives the electron transport chain.
• ATP Breakdown:
  • ATP
    ightharpoonup ADP Cleaving one phosphate group generates 7.3 kilocalories of energy.
• Reverse Reaction:
  • Adding a phosphate group requires energy (net-zero gain).

Carbon Dioxide Production

• Carbon Dioxide Production Per Cycle:
  • Two CO_2 molecules are produced per turn of the cycle.
• Glucose Molecule:
  • One glucose molecule yields two pyruvate molecules.
  • Two pyruvate molecules allow two turns of the cycle, producing a total of four CO_2 molecules.

ATP Production Location

• Majority of ATP:
  • Produced in the electron transport chain.
• Enzymatic Activity Requirement:
  • Significant enzymatic activity is required to drive the process.

Enzyme Deficiencies

• Example:
  • G6PD (glucose-6-phosphate dehydrogenase) deficiency leads to hemolysis of red blood cells.

Creatine Phosphate

• Full Name:
  • Creatine phosphate.
• Storage:
  • Stored in muscles and liver.
• Function:
  • Donates a phosphate group to ADP to regenerate ATP.
• Performance Boost:
  • Provides short bursts of energy, not suitable for long-distance activities like marathons.
• Carbo-Loading:
  • Consuming high amounts of carbs the night before endurance events.
• Reaction:
  • Creatine phosphate hydrolyzes, providing energy for ADP to ATP regeneration.
  • Creatine is then excreted in urine.

Coenzymes

• NAD/NADH:
  • NAD^+:
    • Donates an electron
  • NADH:
    • Needs hydrogen. It is either a loss or gain of hydrogen.
• FAD/FADH2:
  • FADH is two hydrogens.
  • FADH is derived from riboflavin (vitamin B2), which contributes to energy production in energy drinks.

Citric Acid Cycle Products and Steps

• Eight Steps Yield:
  • 3 NADH, 1 FADH2, and 2 CO_2.
  • Intermediates: citrate, isocitrate, alpha-ketoglutarate, fumarate, malate, and oxaloacetate.
• Exercise Science:
  • Clinically relevant.
• Totals Per Cycle:
  • Two CO_2, three NADH, and one FADH.
• Glucose Molecule:
  • If calculated per glucose molecule (two cycles), multiply the per-cycle values by two.

Electron Transport Chain Location

• Location:
  • Inner membrane of the mitochondria.
  • Coenzyme Q10 (CoQ10) functions within this chain.
• Process:
  • NADH and FADH donate hydrogens. This pumping from the matrix occurs at complexes I, III, and IV.
  • These hydrogens are pumped into the intermembrane space. The H^+ gradient drives ATP production.

Oxidative Phosphorylation

• ATP Synthesis:
  • ATP is synthesized during oxidative phosphorylation. Hydrogen is pumped back inside, using potential energy to drive ATP production from ADP.
• ATP Synthase:
  • The enzyme ATP synthase facilitates the conversion of ADP to ATP.
• Cell Death:
  • ATP is not synthesized when a cell dies.

Rigor Mortis

• Mechanism:
  • After death, cells cannot pump calcium or potassium ions.
  • Calcium binds to myosin, causing muscle contraction.
  • ATP is needed to release the myosin head and relax the muscle.
  • Since ATP isn't produced, muscles remain contracted (stiff).
  • Rigor mortis eventually resolves as calcium is released.

Review for Quiz

• Metabolism:
  • Definition of metabolism.
• Mitochondria:
  • Number varies in different cells based on activity level.
  • Structure: inner membrane, intermembrane space, outer membrane, matrix.
  • Functions within these compartments.
• Carbohydrate Digestion:
  • Amylase begins digestion in the mouth.
• Protein Digestion:
  • Occurs in the stomach.
• Fat Digestion:
  • Begins in the duodenum with pancreatic lipase.
• Polysaccharides:
  • Broken down into monosaccharides (catabolic process).
• Quantities Per Cycle:
  • 2 CO_2, 3 NADH, 1 FADH.
• Purpose of the TCA Cycle:
  • To produce reactants (CO_2, NADH, FADH) for the electron transport chain.
• Creatine Phosphate:
  • Donates a phosphate group for quick ATP regeneration in muscles.
• Metabolic Rate:
  • Dependent on demand (e.g., low during rest or sleep).

Key Concepts Review

• Catabolic vs. Anabolic:
  • Both are types of metabolism; understand the distinction.
• Citric Acid Cycle:
  • Circular pathway.
• ATP and Enzymatic Reactions:
  • ATP is needed to make ATP.
  • Enzymes facilitates most of the bio-chemical reactions, like breaking down a resin (raw material) into products like toys.
• Bile Production and Function:
  • Bile is made in the liver and emulsifies fats.
• Carbohydrate Digestion:
  • Amylase in the mouth initiates carbohydrate digestion.
• Electron Transport Chain:
  • NADH, FADH deliver hydrogen ions. The potential energy in the form of a proton gradient facilitates ADP phosphorylation using ATP synthase.