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Biochemistry

🧬biochemistry review

12.1 Glycolysis Pathway and Regulation

Last Updated on August 9, 2024

Glycolysis is the sugar-splitting process that kicks off cellular energy production. It breaks down glucose into pyruvate, generating ATP and NADH along the way. This pathway sets the stage for further energy extraction in later metabolic processes.

Glycolysis consists of two main phases: prep and payoff. The prep phase uses energy to modify glucose, while the payoff phase generates ATP and NADH. Key enzymes regulate the pathway's speed based on the cell's energy needs.

Glycolysis Overview

Glucose Breakdown and Energy Production

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  • Glycolysis breaks down glucose into pyruvate through a series of enzymatic reactions
  • Process occurs in the cytoplasm of cells and does not require oxygen
  • Generates 2 ATP molecules and 2 NADH molecules per glucose molecule
  • Produces 2 pyruvate molecules as the end product of glucose breakdown
  • Serves as a central metabolic pathway for many organisms (bacteria, plants, animals)

Energy Yield and Cellular Implications

  • Net energy yield of glycolysis includes 2 ATP and 2 NADH per glucose molecule
  • ATP produced through substrate-level phosphorylation during the payoff phase
  • NADH carries electrons and serves as a reducing agent in other metabolic processes
  • Pyruvate can enter various metabolic pathways depending on cellular conditions (aerobic respiration, fermentation)
  • Glycolysis provides intermediates for other biosynthetic pathways (amino acids, nucleotides)

Glycolysis Enzymes

Key Regulatory Enzymes

  • Hexokinase catalyzes the first step of glycolysis, phosphorylating glucose to glucose-6-phosphate
  • Phosphofructokinase (PFK) converts fructose-6-phosphate to fructose-1,6-bisphosphate
  • Pyruvate kinase catalyzes the final step, converting phosphoenolpyruvate to pyruvate
  • These enzymes are regulated by allosteric effectors and covalent modifications

Allosteric Regulation Mechanisms

  • Allosteric regulation involves binding of effector molecules at sites distinct from the active site
  • Positive allosteric effectors enhance enzyme activity (AMP activates PFK)
  • Negative allosteric effectors inhibit enzyme activity (ATP inhibits PFK)
  • Feedback inhibition occurs when pathway end products inhibit earlier enzymes (ATP inhibits hexokinase)
  • Allosteric regulation allows for rapid and reversible control of glycolysis in response to cellular energy needs

Glycolysis Phases

Preparatory Phase (Energy Investment)

  • First five reactions of glycolysis consume energy to modify glucose
  • Glucose is phosphorylated by hexokinase to form glucose-6-phosphate
  • Phosphoglucose isomerase converts glucose-6-phosphate to fructose-6-phosphate
  • Phosphofructokinase adds a second phosphate group to form fructose-1,6-bisphosphate
  • Aldolase cleaves fructose-1,6-bisphosphate into two three-carbon molecules
  • Triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde-3-phosphate

Payoff Phase (Energy Generation)

  • Final five reactions of glycolysis generate energy in the form of ATP and NADH
  • Glyceraldehyde-3-phosphate dehydrogenase oxidizes and phosphorylates glyceraldehyde-3-phosphate, producing NADH
  • Phosphoglycerate kinase generates the first ATP molecule through substrate-level phosphorylation
  • Phosphoglycerate mutase and enolase prepare the substrate for the final reaction
  • Pyruvate kinase catalyzes the formation of pyruvate and generates the second ATP molecule
  • Substrate-level phosphorylation directly transfers a phosphate group from a substrate to ADP, forming ATP