Metabolism

• Aerobic respiration:

  • Inputs: glucose
  • Outputs: ATP
  • Key steps: glycolysis, pyruvate dehydrogenase complex, citric acid cycle
• Carbohydrate metabolism goal: Convert glucose into usable energy in the form of ATP
• Glycolysis:

  • Functions: split glucose into pyruvate, reduce NAD+ to NADH, generate ATP from ADP
  • Inputs: 1 glucose, 2 NAD+, 2 ATP
  • Outputs: 2 pyruvate, 2 NADH, 4 ATP
• Energy Investment Phase:

  • Hexokinase phosphorylates glucose
  • Conversion of isomers: G6P into fructose-6-phosphate
  • Conversion F6P into fructose 1,6-bisphosphate by PFK-1
  • F 1,6BP is cleaved into G3P and DHAP
• Energy Payoff Phase:

  • Conversion of G3P into 1,3-bisphosphoglycerate, reducing NAD+ to NADH (substrate level phosphorylation)
  • Transfer of a phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP
  • Rearrangement of 3-phosphoglycerate into PEP
  • Transfer of a phosphate from PEP to ADP, forming ATP and pyruvate
• Pyruvate Dehydrogenase Complex:

  • Transport into mitochondrial matrix via carrier proteins
  • Pyruvate is decarboxylated to form acetyl-CoA
  • Inputs: pyruvate, NAD+
  • Outputs: Acetyl-CoA, NADH
• Citric Acid Cycle:

  • Acetyl-CoA fused with oxaloacetate to form citrate
  • Reduction of electron carriers and formation of GTP
  • Inputs (each turn): 1 pyruvate, 3 NAD+, 1 FAD
  • Outputs (each turn): 1 GTP, 3 NADH, 1 FADH2, 2 CO2
• Gluconeogenesis:

  • Creates glucose from non-carbohydrate sources
  • Occurs in the liver and kidneys
  • Pyruvate is starting point, which comes from various sources, not products of glycolysis
  • bypasses irreversible steps of glycolysis
• Regulation Of Glycolysis:

  • Negative feedback regulation, hormone regulation, allosteric regulation
  • Three main regulatory steps: Phosphofructokinase, Hexokinase, pyruvate kinase
• PDC regulation:

  Cells needing energy: High levels of AMP, coenzyme A and NAD+ upregulate PDC

  Cells with surplus of energy regulate via feedback inhibition (high ATP, NADH, or acetyl-CoA downregulate PDC)
• Electron Transport Chain Disruption:

  • Cyanide inhibition of Cytochrome C
  • 2,4-Dinitrophenol and ATP synthase bypass
• Anabolic reactions build up larger molecules from simpler ones using the released energy.
• Catabolic reactions break down molecules into smaller units to release energy.
• Glycolysis occurs in the cytosol of the cell
• Glycolysis functions:

  -involves breakdown of glucose (6 carbons) into two pyruvate (3 carbons)

  -split glucose into 2 pyruvate

  -Reduces NAD+ to NADH

  -Generate 2 ATP per 1 glucose
• Glycolysis: Net production of 2 ATP molecules per glucose molecule
• Energy investment phase utilizes 2 ATP molecules to begin breakdown of glucose
• Energy payoff phase results in 2 molecules of pyruvate, 2 NADH, and a net gain of 4 ATP per glucose
• In aerobic cellular conditions, pyruvate enters the citric acid cycle, NADH goes to the electron transport chain for more ATP production
• In anaerobic cellular conditions, fermentation process regenerates NAD+ and allows glycolysis to continue
• Insulin upregulates glycolysis; glucagon downregulates glycolysis
• Gluconeogenesis occurs when blood glucose levels are low
• High ratio ATP to ADP/AMP downregulates glycolysis; low ratio of ATP to ADP/AMP upregulates glycolysis
• High levels of citrate and NADH downregulates glycolysis. this indicates an abundance of energy resources
• Hexokinase is inhibited by glucose-6-phosphate (negative feedback inhibition)
• PFK-1 inhibited by ATP and citrate; activated by AMP; controlled by fructose 2,6-bisphosphate (allosteric effector)
• Hexokinase, phosphofructose kinase, and pyruvate kinase are regulatory steps in glycolysis
• Pyruvate kinase inhibited by ATP, acetyl CoA, and fatty acids (negative feedback inhibition)
• The liver produces most of the glucose needed during fasting through gluconeogenesis.
• Lactic acid fermentation involves the reduction of pyruvate to lactic acid via lactate dehydrogenase; recycles NADH to NAD+ to sustain glycolysis in anaerobic conditions
• Ethanol fermentation is two-step pathway characteristic in yeast, brewing, and food fermentation. Regenerates NAD+ from NADH to sustain glycolysis during anaerobic conditions

  1. Pyruvate decarboxylation to acetaldehyde with CO2 release by pyruvate decarboxylase
  2. Reduction of acetaldehyde to ethanol by alcohol dehydrogenase
• Substrates for gluconeogenesis:

  • protein via amino acid convertion
  • glycerol from FA breakdown
  • lactate from lactic acid fermentation
• First step in gluconeogenesis: pyruvate to oxaloacetate by pyruvate decarboxylase in mitochondria

  -malate shuttle transports oxaloacetate back to cytosol

  Second step: oxaloacetate to PEP by PEP carboxykinase in cytosol
• Key bypass reactions in gluconeogenesis:

  • first step: conversion of pyruvate to oxaloacetate then to PEP
  • hydrolysis of fructose 1,6-biphosphate to fructose 6-phosphate by fructose 1,6-biphosphatase
  • isomerization of F6P back to G6P, followed by the formation of glucose by glucose 6-phosphatase
• High acetyl-Coa downregulates pyruvate's conversion to acetyl-Coa in mitochondria, causing pyruvate to be diverted towards gluconeogenesis
• Glucagon reduces levels of F2,6-BP, promoting gluconeogenesis
• Insulin activates F2,6-BP, inhibiting gluconeogenesis
• High levels of F2,6-BP inhibits gluconeogenesis (via F1,6BPhostaphase) and activates glyclolysis (via PFK1)
• High AMP indicates low energy, inhibiting gluconeogenesis
• Inner mitochondrial membrane is impermeable to most substances except H2O and small gas molecules