Biochem Lecture 12

Reminder for Upcoming Exam

  • Exam labeled "Exam Two" will occur soon.

  • Coverage:

    • Material from Wednesday's lecture.

  • Schedule:

    • Study period from Wednesday until Monday.

    • Review session details provided.

  • Resources:

    • Practice exams uploaded online for review.

    • Specific rooms designated based on last name for exam.

    • New cheat sheet provided.

Glycolysis Overview

  • Glycolysis completes the breakdown of glucose into pyruvate.

  • Process breakdown:

    • One glucose molecule (6 carbons) -> Two pyruvate molecules (3 carbons each).

    • Produces:

      • 2 ATP directly

      • 2 NADH (reduced coenzyme) for energy production (if oxygen present).

Challenges in Glycolysis

  • Maintaining glycolysis in the presence of limited resources:

    • Source of glucose:

      • Obtained from the diet and digestion.

    • Fate of pyruvate produced must be addressed (does not accumulate).

  • Regeneration of NAD+ needed for glycolysis to continue beyond initial glycolytic reactions.

Source of Glucose

  • Glucose is primarily derived from dietary carbohydrates:

    • Disaccharides: Hydrolyzed to monosaccharides for glycolysis.

      • Sucrose -> glucose and fructose (hydrolized by sucrose).

      • Lactose -> glucose and galactose (hydrolized by lactase).

  • Evolutionary Adaptation:

    • Lactase is only beneficial in infants; nutrient adaptation influenced human digestion capability in adults.

    • Some adults lack lactase, leading to lactose intolerance, and solutions like lactose-free milk exist.

Polysaccharide Breakdown

  • Dietary starches (e.g., potatoes, rice) are polymers of glucose.

  • Glycogen as a storage form of glucose in liver/muscle tissues.

  • Glycogen breakdown:

    • Glycogen phosphorylase utilizes phosphorylation over hydrolysis to release glucose-1-phosphate directly.

    • Branching enzyme manages branched glycogen structures for efficient breakdown to glucose-6-phosphate to enter glycolysis.

Utilization of Pyruvate

  • Under aerobic conditions:

    • Pyruvate is converted to acetyl-CoA, leading through the TCA cycle.

    • Six carbon atoms from glucose are fully oxidized to carbon dioxide (4 CO2 produced overall).

  • Under anaerobic conditions:

    • Fermentation processes regenerate NAD+:

      • In yeast: Pyruvate -> CO2 + Acetaldehyde -> Ethanol + NAD+.

      • In muscle cells: Pyruvate -> Lactate + NAD+ (causes muscle cramping if it builds up).

The TCA Cycle Introduction

  • Acetyl-CoA functions as the entry molecule for the TCA cycle in aerobic metabolism:

    • Intermediates of metabolites (from carbohydrates/fats) converge into this cycle.

    • Energy is harvested through NADH and FADH2, which are essential for aerobic energy production.

Key Steps in the TCA Cycle

  • Condensing enzyme (Citrate Synthase):

    • Acetyl-CoA + Oxaloacetate -> Citrate (6 carbons).

  • Aconitase Reaction:

    • Rearranges citrate to isocitrate.

  • Isocitrate Dehydrogenase Reaction:

    • Oxidation and decarboxylation of isocitrate to reduce NAD+ to NADH and release CO2.

  • Alpha-Ketoglutarate Dehydrogenase Reaction:

    • Alpha-ketoglutarate (5 carbons) undergoes another decarboxylation and reduction to NADH and succinyl-CoA.

  • Succinyl-CoA Synthetase Reaction:

    • Converts succinyl-CoA to succinate; generates GTP through substrate-level phosphorylation.

  • Succinate Dehydrogenase Reaction:

    • Succinate -> Fumarate + FADH2.

  • Fumarase Reaction:

    • Fumarate + H2O -> Malate.

  • Malate Dehydrogenase Reaction:

    • Oxidation of malate to regenerate oxaloacetate + NADH.

Net Outputs of the TCA Cycle

  • Inputs yield:

    • 2 carbons via Acetyl-CoA.

    • Release of 2 CO2.

    • Production of 3 NADH, 1 FADH2, and 1 GTP (equivalent to ATP).

Summary

  • Energy production is maximized via glycolysis and TCA cycle, linking carbohydrates and fats metabolism.

  • Understanding pyruvate and glucose metabolism essential for efficient ATP generation under various conditions.