Chapter 9. Cellular Respiration STAGE 1: Glycolysis

What’s the point? ATP The Point is to Make ATP!

glucose      pyruvate Glycolysis Breaking down glucose “glyco – lysis” (splitting sugar) most ancient form of energy capture starting point for all cellular respiration inefficient generate only 2 ATP for every 1 glucose in cytosol why does that make evolutionary sense? glucose      pyruvate 6C 2x 3C Why does it make sense that this happens in the cytosol? Who evolved first?

Evolutionary perspective Life on Earth first evolved without free oxygen (O2) in atmosphere energy had to be captured from organic molecules in absence of O2 Organisms that evolved glycolysis are ancestors of all modern life all organisms still utilize glycolysis You mean, I’m related to them?! 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

Overview glucose C-C-C-C-C-C fructose-6P P-C-C-C-C-C-C-P DHAP P-C-C-C activation energy 10 reactions convert 6C glucose to two 3C pyruvate produce 2 ATP & 2 NADH 2 ATP 2 ADP fructose-6P P-C-C-C-C-C-C-P DHAP P-C-C-C PGAL C-C-C-P 1st ATP used is like a match to light a fire… initiation energy / activation energy. Destabilizes glucose enough to split it in two 2 NAD+ 2 NADH 4 ADP 4 ATP pyruvate C-C-C 2005-2006

Glycolysis summary endergonic invest some ATP exergonic harvest a little more ATP & a little NADH 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.

1st half of glycolysis (5 reactions) Glucose “priming” get glucose ready to split phosphorylate glucose rearrangement split destabilized glucose PGAL Pay attention to the enzymes!

2nd half of glycolysis (5 reactions) Oxidation G3P donates H NAD  NADH ATP generation G3P  pyruvate donates P ADP  ATP Payola! Finally some ATP! 2005-2006

OVERVIEW OF GLYCOLYSIS 1 2 3 6-carbon glucose (Starting material) 2 ATP P P P P 6-carbon sugar diphosphate 6-carbon sugar diphosphate P P P P 3-carbon sugar phosphate 3-carbon sugar phosphate 3-carbon sugar phosphate 3-carbon sugar phosphate NADH NADH 2 ATP 2 ATP 3-carbon pyruvate 3-carbon pyruvate Priming reactions. Priming reactions. Glycolysis begins with the addition of energy. Two high-energy phosphates from two molecules of ATP are added to the six-carbon molecule glucose, producing a six-carbon molecule with two phosphates. Cleavage reactions. Then, the six-carbon molecule with two phosphates is split in two, forming two three-carbon sugar phosphates. Energy-harvesting reactions. Finally, in a series of reactions, each of the two three-carbon sugar phosphates is converted to pyruvate. In the process, an energy-rich hydrogen is harvested as NADH, and two ATP molecules are formed. 2005-2006

Substrate-level Phosphorylation In the last step of glycolysis, where did the P come from to make ATP? P is transferred from PEP to ADP kinase enzyme ADP  ATP I get it! The P came directly from the substrate! 2005-2006

Energy accounting of glycolysis 2 ATP 2 ADP glucose      pyruvate 6C 2x 3C 4 ADP 4 ATP All that work! And that’s all I get? 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

Heck of a way to make a living! Is that all there is? Not a lot of energy… for 1 billon years+ this is how life on Earth survived only harvest 3.5% of energy stored in glucose slow growth, slow reproduction Heck of a way to make a living! So why does glycolysis still take place?

We can’t stop there…. Glycolysis NADH glucose + 2ADP + 2Pi + 2 NAD+  2 pyruvate + 2ATP + 2NADH Going to run out of NAD+ How is NADH recycled to NAD+? without regenerating NAD+, energy production would stop another molecule must accept H from NADH NADH 2005-2006

How is NADH recycled to NAD+? Another molecule must accept H from NADH aerobic respiration ethanol fermentation lactic acid fermentation NADH 2005-2006

Anaerobic ethanol fermentation Bacteria, yeast 1C 3C 2C pyruvate  ethanol + CO2 NADH NAD+ beer, wine, bread at ~12% ethanol, kills yeast Animals, some fungi Count the carbons!! Lactic acid is not a dead end like ethanol. Once you have O2 again, lactate is converted back to pyruvate by the liver and fed to the Kreb’s cycle. pyruvate  lactic acid 3C NADH NAD+ cheese, yogurt, anaerobic exercise (no O2) 2005-2006

Pyruvate is a branching point fermentation Kreb’s cycle mitochondria

What’s the point? ATP The Point is to Make ATP!

Any Questions??