I. Cellular Respiration Stage 1: Glycolysis

What’s the point? The point is to make ATP! ATP

Glycolysis Breaking down glucose “glyco – lysis” (sugar splitting) Oxidation of a hexose sugar (glucose, 6 carbons) to 2 pyruvate (3 carbons) is coupled to the reduction of ADP to ATP. But it’s inefficient Generate only 2 ATP for every 1 glucose Occurs in cytosol Why does it make sense that this happens in the cytosol? Who evolved first?

Evolutionary perspective Prokaryotes First cells had no organelles Anaerobic atmosphere Life on Earth first evolved without free oxygen (O2) in atmosphere. Energy had to be captured from organic molecules in absence of O2. Prokaryotes that evolved glycolysis are ancestors of all modern life. ALL cells still utilize glycolysis. The enzymes of glycolysis are very similar among all organisms. The genes that code for them are highly conserved. They are a good measure for evolutionary studies. Compare eukaryotes, bacteria & archaea using glycolysis enzymes. Bacteria = 3.5 billion years ago glycolysis in cytosol = doesn’t require a membrane-bound organelle O2 = 2.7 billion years ago photosynthetic bacteria / proto-blue-green algae Eukaryotes = 1.5 billion years ago membrane-bound organelles! Processes that all life/organisms share: Protein synthesis Glycolysis DNA replication

II. Overview glucose C-C-C-C-C-C 10 reactions in 3 basic steps: ATP 2 enzyme 10 reactions in 3 basic steps: Phosphorylation or “Energy Investment” phase Lysis Oxidation/ATP formation or “Energy Payoff” phase ADP 2 enzyme fructose-1,6bP P-C-C-C-C-C-C-P enzyme enzyme enzyme DHAP P-C-C-C G3P C-C-C-P NAD+ 2 2H 2Pi 1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two enzyme 2 enzyme ADP 4 2Pi enzyme ATP 4 pyruvate C-C-C

Phosphorylation (Energy investment) Hexose sugar (glucose, 6 carbons) is phosphorylated to hexose diphosphate. Also called Fructose-1,6-biphosphate Requires input of 2 ATP molecules

The phosphate groups allow a stronger interaction between the hexose and its enzyme. The energy content of hexose biphosphate is higher than glucose.

Lysis Hexose biphosphate breaks into two triose phosphate (TP) molecules. Also called Glyceraldehyde-3-phosphate (G3P) or Glycerate-3-phosphate (IB book term)

Lysis G3P (or TP) is an intermediate in many biochemical reactions. Phosphate group allows the sugar to form stronger interaction with the next enzyme in the pathway.

Oxidation/ATP Formation (Energy Payoff) Is the main oxidative stage of glycolysis which results in the formation of ATP and NADH + H+. Each G3P (TP) is oxidized to a 3-carbon molecule called pyruvate. Each G3P (TP) has hydrogen removed (oxidation) to reduce 1 NAD+ to NADH. Each G3P (TP) adds a phosphate to ADP reducing it to ATP; Done 2x for each G3P This phase produces 4 ATP and 2 NADH.

(Nothing to write; Just look!) endergonic invest some ATP ENERGY INVESTMENT G3P C-C-C-P exergonic harvest a little ATP & a little NADH ENERGY PAYOFF 4ATP Glucose is a stable molecule it needs an activation energy to break it apart. phosphorylate it = Pi comes from ATP. make NADH & put it in the bank for later. yield 2 ATP 2 NADH 2 H+ 2 pyruvate like $$ in the bank NET YIELD

III. Glycolysis Summary Energy accounting of glycolysis 2 ATP 2 ADP glucose      pyruvate 6C 2x 3C 4 ADP ATP 4 And that’s how life subsisted for a billion years. Until a certain bacteria ”learned” how to metabolize O2; which was previously a poison. But now pyruvate is not the end of the process Pyruvate still has a lot of energy in it that has not been captured. It still has 3 carbons bonded together! There is still energy stored in those bonds. It can still be oxidized further. Net gain = 2 ATP Some energy investment (-2 ATP) Small energy return (+4 ATP) 1 6C sugar  2 3C sugars

Energy accounting of glycolysis 2 ATP 2 ADP glucose      pyruvate 6C 2x 3C 4 ADP ATP 4 And that’s how life subsisted for a billion years. Until a certain bacteria ”learned” how to metabolize O2; which was previously a poison. But now pyruvate is not the end of the process Pyruvate still has a lot of energy in it that has not been captured. It still has 3 carbons bonded together! There is still energy stored in those bonds. It can still be oxidized further. Two NADH + H+ are produced which will yield more ATP when they are transferred to the mitochondria and oxidative phosphorylation.

Is that all there is? Not a lot of energy… For 1 billon years+ this is how life on Earth survived No O2= slow growth, slow reproduction Only harvest 3.5% of energy stored in glucose More carbons to strip off = more energy to harvest O2 glucose     pyruvate O2 So why does glycolysis still take place? 6C 2x 3C O2 O2 O2