tumour metabolism

• why do cancer cells metabolise differently?

  • do not have normal blood supply
  • proliferating
  • different genome - turned off genomes
• how many net ATP made in respiration

  38
• glycolysis

  • net ATP = 2
  • 4 ATP produced in total
  • 2NADH
  • 2 pyruvate
• respiration excluding glycolysis

  • 36 ATP
  • 8NADH
  • 2FADH2
  • 2GTP
• glycolysis input + output per glucose

  • glucose + 2ATP -> 2 pyruvate + 2ATP + 2NADH
• respiration

  • catabolic
  • oxidation of glucose
  • multiple steps -> captured by activated carriers
• Where does respiration occur?

  mitochondria
• Cellular Respiration

  C6H12O6 + 6O2 -> 6H2O + 6CO2 + ATP
• glycolysis

  • cytosol
  • energy investment + payoff
  • energetically unfavorable but allows instant ATP release
• nad+ -> nadh

  reduction
• use of glycolysis 2nadh

  used in oxidative phosphorylation

  transported to inner mitochondrial membrane
• link reaction

  pyruvate -> NADH + CO2 + acetylcoA
• free fatty acids can be converted into coA
• link reaction

  • mitochondrial matrix
  • decarboxylated in pdh complex
• structure of a mitochondria

  • pores + pumps
  • ribosome
  • ATP synthase
  • inner/outer membrane
  • intermembrane space
  • cristae
• how respiration can generate products for anabolic pathways?

  • nucleotides
  • amino acids (glutamate, aspartate)
  • glyco lipids/proteins
  • lipids
  • cholesterol
• gtp

  2co + atp
• krebs cycle

  • 3nadh + fadh2 + gtp
  • 3nadh + fadh2 + 2co + atp
  • NADH + ATP + FADH2 + CO2
• location of krebs cycle

  mitochondria
• why does the krebs cycle not require o2 from the atmosphere?

  present in water
• no enzyme that oxidises 2C molecules (acetate)
• why is the krebs cycle not a cycle

  oxaloacetate regenerated
• krebs cycle

  subsequent oxidation releases energy to activated carriers
• adp + p -> atp + h2o
• electron carriers nadh + fadh2 transfer high energy electrons into etc
• anabolic = biosynthetic
• advantages of tumour metabolism despite its poor metabolism

  • environment irrelevant
  • avoids radiotherapy
  • more proliferation
  • clonally selects (more resistant survives)
  • hypoxic environments
• location of oxidative phosphorylation

  inner mitochondrial membrane
• oxidative phosphorylation

  • electron donor/acceptor reaction that drives proton into intermembrane space (acidic)
  • from matrix
• krebs cycle is aerobic process
• 4 Carbon-Carbon bonds remains in krebs cycle
• ATP produced in Oxidative Phosphorylation

  • net = 36
  • total = 38
• How many molecules of Acetyl Co-Enzyme A are made per molecule of glucose

  2
• Warburg effect generates 4 ATP/mol of glucose
• warburg effect - aerobic glycolysis

  • lactase production
  • high glucose utilisation
  • low oxygen levels
• consequences of warburg effect

  • overexpression of hexokinase
  • depletion of krebs cycle
• aerobic conditions

  lactate -> pyruvate

  
  

  nadh -> nad oxidation

  
  

  lactate dehydrogenase
• hypoxic

  • lactate excreted from cells
  • increased activity pkm2 - slower than pkm1
  • buildup of lactate + nadh
  • inhibits glycolysis
  • increased acidity
• tumour metabolism

  • glut1 glucose transporter hyperactive
  • increased glucose delivery
  • biosynthetic dominant glycolysis intermediates produced
  • HIF signaling enzymes shifts towards pyruvate metabolism
  • mitochondrial stages blocked
  • mostly 'anaerobic' process
• differences in metabolism in tumours as metabolism reprogammed

  • tf cMyc
  • Ras
  • p53
  • stabilise HIF, as hypoxia