Wk 2 Glycolosis.pdf

BIOL214 Week 2 - Lecture 3: Glycolysis Dr. Jay Perry [email protected]  Schedule of learning Module 1 – Carbohydrate metabolism 2 Metabolism doesn’t work in isolation 3  The Ri...

BIOL214 Week 2 - Lecture 3: Glycolysis Dr. Jay Perry [email protected]  Schedule of learning Module 1 – Carbohydrate metabolism 2 Metabolism doesn’t work in isolation 3  The Rise of Biochemistry Influencers Disclaimer: The following list is for illustrative purposes only and does not constitute a ranking, endorsement, or criticism 2nd Disclaimer: My algorithm is likely weighted towards male-centric health information, hence one reason for the disparity in representation Pete Evans Dr Paul Liver King A/Prof Andrew Dr Rhonda Dr Peter Attia Saladino Huberman Patrick Glucose Dr Mike Prof David Dr Gabrielle VShred The entirety Goddess Israetel Sinclair Lyon of TikTok 4 For interest only  Carbohydrate Metabolism Week 4 Week 5 Weeks 2-3 5  Lecture objectives (re)introduce cellular respiration Understand the essential features of the glycolysis pathway – Reduction of NAD+, production of ATP and pyruvate Know the vital steps in glycolysis Know about other metabolic fates of pyruvate 6  Lecture objectives (re)introduce cellular respiration Understand the essential features of the glycolysis pathway – Reduction of NAD+, production of ATP and pyruvate Know the vital steps in glycolysis Know about other metabolic fates of pyruvate 7 Available on the Moodle site 8  Cellular respiration Process in which cells breakdown glucose to form ATP Adenosine tri-phosphate (ATP) is the energy currency of organisms Occurs in three major stages: - ➀ acetyl CoA production (glycolysis) - ➁ acetyl CoA oxidation (TCA cycle) - ➂ electron transfer/oxidative phosphorylation Other precursors can be amino acids and glycerol, but relax on that for now 9  Cellular respiration How much ATP do you make from 1 snake lolly? (theoretically) Glucose amount = 5.45 grams Molecular mass of glucose = 180.16 g/mol Moles of glucose = 5.45 g/180.16g/mol = 0.0302508 Molecules of glucose = 0.0302508 moles X 6.022x1023 (Avogadro’s #) = 1.822x1022 molecules You make your body weight in ATP each day! If 1 glucose molecule makes 38 ATP… 38 ATP X 1.822x1022 molecules = 6.92x1023 ATP or… 692,000,000,000,000,000,000,000 ATP molecules! Even at 50% efficiency, that’s a lot of ATP. 10 For interest only – I would never ask you to perform this calculation. Yuck. Cellular respiration ➀ acetyl-CoA production In the cytoplasm ➁ acetyl-CoA oxidation In the mitochondrial matrix ➂ Oxidative Phosphorylation In the inner mitochondrial membrane 11  Lecture objectives (re)introduce cellular respiration Understand the essential features of the glycolysis pathway – Reduction of NAD+, production of ATP and pyruvate Know the vital steps in glycolysis Know about other metabolic fates of pyruvate 12  Glycolysis mer = part Glycolysis; Greek iso = same ase = enzyme Glykis = “sweet”, ose = sugar genesis = development Lysis = “splitting” neo = new osis = disease/condition Breaking apart the meaning of a word can help de = removal a lot in understanding biochemistry! ation = action of doing Occurs in the cytosol of every cell Energy is released from glucose and captured as ATP/NADH Serves as a model to understand many metabolic pathways 13  Glycolysis summary Glucose 2 x Pyruvate 10 reactions e- H+ Pi + 2NAD+ +2ADP +2PO43- + 2NADH +2H+ + 2ATP + 2H2O 14  The importance of glycolysis 1. Main method of creating Acetyl-CoA 2. Glucose is the only metabolic energy source for: Tissues: brain, kidney, & rapidly contracting skeletal muscles Cells: erythrocytes & sperm cells 3. Tightly regulated – as ATP hydrolyses easily, we can use glycolysis to regulate ATP production 15 Glycolysis overview 16 Glycolysis overview 17  1. Phosphorylation of glucose ✪ This is an important regulatory enzyme; Know this reaction; know names and structures (G6P) cytosol Chemical logic: Happens at C6 as C1 is a carbonyl (C=O) and can’t be phosphorylated 18  2. Conversion of G6P to Fructose-6-phosphate (F6P) Isomerization: a reaction that changes the shape of a single molecule but doesn't permanently add or remove any atoms. (F6P) Chemical logic: isomerisation moves carbonyl to C2, prep for next step 19 3. Phosphorylation of F6P to Fructose-1,6-bisphosphate ✪ This is an important regulatory enzyme; Know this reaction; know names and structures (F-1,6-BP) PFK-1 = “gatekeeper” of glycolysis (committed step) Mutations associated with cancer Chemical logic: phosphorylates so both ends have a phosphate and interconvertible once cleaved 20  4. Cleavage of fructose-1,6-bisphosphate (F-1,6-BP) (G3P) Chemical logic: bunch of steps to chop this bad boy up 21  5. Interconversion of the triose phosphates Now we have 2 of these! (G3P) Chemical logic: rearranges dihydroxyacetone phosphate to G3P to funnel both products into a single pathway 22  Glycolysis overview How it started: Let’s make ATP! How it’s going: We’re down 2 ATP 23 6. Oxidation of G3P to 1,3-bisphophoglycerate (1,3-BPG) inorganic phosphate introduced (not from ATP) NAD+ is a cofactor here NADH produced is to be used in oxidative phosphorylation (or to make lactate) Chemical logic: pinches some e- and H and replace with free-floating phosphate so we can make ATP in step 7. 24  Sidebar: ATP synthesis Question: If we have inorganic phosphate floating around, why don’t we just make ATP from AMP/ADP directly? Answer: Complex pathways allow for tight regulation ATP hydrolyses quickly, so cellular respiration allows us to make ATP when needed 25  Sidebar: NAD+  NADH NADH “Life is good” NAD+ NADH+ H H “Hello, I would like “Okay, but we “But I’m still some electrons positive!” “Hello, I’m another have to share” please” hydrogen, you can take my e-, and I guess I’ll just float around lonely” 26  7. Phosphoryl transfer from 1,3-BPG to ADP (3GP) Chemical logic: Finally, time to make some ATP 27  8. Conversion of (3-PG) to 2-phosphoglycerate Chemical logic: Sets up final steps by moving the phosphoryl group 28  9. Dehydration of 2-PG to phosphoenolpyruvate (PEP) Chemical logic: Dehydration activates the phosphoryl for transfer to ADP in next step 29  10. Transfer of phosphoryl group from PEP to ADP ✪ This is an important regulatory enzyme; Know this reaction; know names and structures(~ish) Chemical logic: ATP production 30 31  Glycolysis is elevated in tumour cells Tumour cells can grow faster than a blood supply can be made  leads to anaerobic You don’t need to memorise this figure metabolism Only 2 ATP made in anaerobic conditions, so cancer cells must ramp up glycolysis E.g. glucose transporters, hexokinase Compounds that inhibit key steps in glycolysis can kill cancer cells by limiting energy production 32  Oxidation of multiple carbohydrates involves glycolysis For interest only For interest only 33  Glycolysis summary Glucose is broken down from a 6-carbon molecule to two 3-carbon molecules called pyruvate There is an investment phase of 2 ATP and a gain of 4 ATP, netting 2 ATP NADH is also produced Key steps include – Step 1. G  G6P (via hexokinase) Irreversible, costs ATP – Step 3. F6P  F1,6-BP (via PFK1) Irreversible, commitment step, highly regulated – Step 10. PEP  Pyruvate (via PK) Irreversible, makes ATP, last step 34  Quick Quiz Glycolysis occurs in the cytoplasm of the cell A net of 4 ATP molecules are produced during glycolysis Aldolase catalyses the hydrolysis of water Phosphofructokinase-1 (PFK1) is a key regulatory enzyme in glycolysis 35  Lecture objectives (re)introduce cellular respiration Understand the essential features of the glycolysis pathway – Reduction of NAD+, production of ATP and pyruvate Know the vital steps in glycolysis Know about other metabolic fates of pyruvate 36  Fates of pyruvate Oxygen is required to unlock the full energy potential of glucose via cellular respiration Next lectures… 37  Fates of pyruvate (anaerobic) Ethanol Lactate production production 38  Ethanol production Yeast are capable of ethanol fermentation Two-step reduction of pyruvate to ethanol Humans do not have pyruvate decarboxylase Humans do have alcohol dehydrogenase 39 Lactate production If no O2 around, ETC can’t accept e- from NADH – process halts So, the cell makes lactate by using all this accumulated NADH feeds NAD+ back into glycolysis until O2 is available Lactate formed by active skeletal muscle can be recycled The Cori cycle – covered in week 4! 40 41  Summary Glycolysis – occurs in the cytosol – from 1 glucose to 2 pyruvate molecules – 2NADH +2H+ + 2ATP generated. – does NOT require O2 – regulated to maintain constant cellular [ATP] – is the only source of ATP for some cell/tissue types – Tumours have very high rates of glycolysis Pyruvate – can be converted to Lactate (anaerobic conditions) – can be converted to ethanol by yeast – can be converted to acetyl-CoA to feed into TCA cycle (next lecture) 42  For visual learners 43 https://education.nationalgeographic.org/resource/cellular-respiration-infographic/  Extra info/resources Dr Matt & Dr Mike: Carbohydrate metabolism | Glycolysis, TCA cycle, & Oxidative phosphorylation Audio (take a stroll in the botanical gardens): https://open.spotify.com/episode/6QXLUPaM2lI6YBFjusVBWb?si=ba1a6c9896d04470 Video: https://www.youtube.com/watch?v=8u0MOOlwkRc&ab_channel=DrMatt%26DrMike Dr Matt & Dr Mike: Glycolysis made easy! https://www.youtube.com/w atch?v=TnQGcKpahfM&ab_ch annel=DrMatt%26DrMike Pg 510 8th Ed. Glycolysis in 2 mins! https://www.tiktok.com/@a_bi Older editions ology_teacher/video/71675595 are fine 35924727082?is_from_webapp =1&sender_device=pc&web_id =7205878264539022849 44 6- bisphosphat e 45 https://www.uow.edu.au/st udent/careers/careers- events/stem-careers-expo/