Glycolysis (Catabolism of Glucose) Flashcards
What is metabolism?
All chemical reactions that maintain the living state of cells and organisms
Anabolism + Catabolism
Define anabolism
Assimilation of molecules and complex structures from building blocks of life
Requires energy
Define catabolism
Breakdown of molecules to obtain the anabolic building blocks of life and substrates for energy
Yields energy
Where does out energy come from?***
From the sun
Plants photosynthesise macromolecules using sunlight as energy
Catabolic pathways oxidise macromolecules, creating ATP
ATP can be used to drive biosynthesic reactions
What are the redox reactions that take place in metabolism? ***
What cells types require glucose as an energy source?
Erythrocytes
Retina
Renal Medulla
Brain
All cancer cells (Warburg Effect)
Name 4 disaccharides
Lactose
Maltose
Sucrose
Cellobiose
What is the lactose bond?
galactose beta-1,4 glucose
What is the maltose bond?
glucose alpha–1,4 glucose
Sucrose
glucose alpha-1,2 fructose
What is the cellobiose bond?
glucose beta-1,4 glucose
What are the 4 fates of glucose?
Storage (glycogen, starch, surcose, conversion to LIPIDS)
Pyruvate by oxidation via aerobic glycolysis
Lactate by fermentation via anaerobic glycolysis
Ribose-5-P by oxidation through Pentose Phosphate Pathway
What is pyruvate needed for?
Effieicnt ATp production by oxidative metabolism
What is lactate needed for?
Rapid, inefficient ATP production
What is ribose-5-P needed for?
Precursor for nucleotide synthesis & DNA repair
Essential for growth
What are the intracellular stages of metabolism?*
Acetyl-CoA production
Acetyl-CoA oxidation
Electron transfer & oxidative phsophorylation
How is glucose transported into cells?
Via Na+/glucose symporters
AND
Via passive facilitated diffusion glucose transporters (GLUT)
What does low Km mean?
High affinity for glucose
Where is GLUT1 found and what is it’s Km?
Brain
Low KM
Same as GLUT3
Where is GLUT2 found and what is it’s Km?
Liver and beta-cells (pancreas)
High KM
Insulin-independent
Where is GLUT3 found and what is it’s Km?
Brain
Low KM
Same as GLUT1
Where is GLUT4 found?
Muscle & adipose
Insulin-indpendent
What is GLUT5 and where is it found?
Fructose transport in GUT
What are the 3 control points and why?
Enzymes catalyzing irreversible reactions
Hexokinase = substrate entry
Phosphofructokinase = rate of flow
Pyruvate Kinase = product exit
What inhibits the 3 control points?
Hexokinase = product inhibition (G6P)
Phosphofuctokinase = ATP (shows enough energy already)
Pyruvate kinase = product inhibition (ATP)
What is phosphofuctosekinase regulated by?
Activators = AMP and fructose-2,6-BP
Inhibitors = ATP, H+, citrate
Why are AMP and fructose-2,6-BP activators of phosphofructokinase?
Increase glycolysis if energy is needed
Why are ATP, H+, citrate inhibtors?
ATP will slow glycolysis if energy is abundant
H+ slows glycolysis if too much lactic acid
Citrate slows downstream pyruvate entry into TCA if energy is abundant
What is energy charge?
ATP/AMP ratio = controls phosphofructokinase
What does the cell being fully charged vs discharged mean?
Fully charged = all adenylate nucleotides are ATP
Discharged if the cell only has AMP and Pi
What happen if mitochondrial metabolism is inhibited by lack of oxygen?
NADH is used to ferment pyruvate to lactate
NADH is regenerated by G3P dehydrogenase (start of stage 3)
When is NADH regenerated?
NADH is regenerated by G3P dehydrogenase (start of stage 3)
What is the Warburg Effect?
Upregulation of anaerobic glycolysis in cancer cells
How do cancer cels produce energy?
ANAEROBIC glycolysis
High rate of GLUCOSE to LACTATE
What relationship do cancer cells have with hexokinase?
Cancer cells have low KM hexokinase meaning they have HIGH affinity for glucose
What are the advantages for anaerobic glycolysis in cancer cells?
Rapid energy production
Supports other pathways for nucleotide sythesis (needed for growth)
Supports rapid cell proliferation
What are the disadvantages for anaerobic glycolysis in cancer cells?
Produces H+ and lactate
Very inefficient ATP synthesis
High glucose comsumption demand
Cancer patients lose weight
How are they treating cancer by targeting glycolysis?
Competitive inhibtors
2-deoxy-glucose = blocks further metabolism of G6P
3-bromopyruvate = block production of 1,3-bisphosphoglycerate
AND
Dichloroacetate = promotes conversion of lactic acid to pyruvate
How does dichloroacetate work? ***
Inhibits pyruvate dehydrogenase kinase
Promotes conversion of lactic acid to pyruvate
By re-engageing mitochondrial metabolism = slows glycolytic rate
Cells can no longer sustain nucleotide synthesis and so cannot grow
