glycolysis chapter 16, stryer short course. glycolysis expectations memorize/learn figure 16.1 –...
TRANSCRIPT
![Page 1: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/1.jpg)
Glycolysis
Chapter 16, Stryer Short Course
![Page 2: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/2.jpg)
Glycolysis Expectations
• Memorize/learn Figure 16.1– Know overall reaction and stages– Explain chemical/physiological purpose of each
step• Learn structures• Reversible/Irreversible step• Chemical names from structures• Enzyme names from structures
![Page 3: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/3.jpg)
Glycolysis
• Ten enzymes that take glucose to pyruvate
• Cytosol• Goal: ATP, NADH,
pyruvate
![Page 4: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/4.jpg)
Energy Input Stage
• Expend 2 ATP• Direct glucose toward
appropriate metabolic path
• Regulation sites• Make two identical 3-
carbon units
![Page 5: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/5.jpg)
Energy Payoff Stage
• Recoup investment– Use energy of oxidation– Store high energy
electrons as NADH– Produce 4 ATP (2 NET
ATP)
• Produce pyruvate– Building block– Ready for further
oxidation pathways
![Page 6: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/6.jpg)
1. Hexokinase
• Irreversible, regulation• Physiological purposes:
![Page 7: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/7.jpg)
Induced Fit
![Page 8: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/8.jpg)
2. Phosphoglucose Isomerase• Near-equilibrium• Chemical purpose
![Page 9: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/9.jpg)
3. Phosphofructokinase-1• Irreversible, regulation• Physiological purpose:
![Page 10: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/10.jpg)
4. Aldolase• DGo’ is +23kJ, but near equilibrium reaction• Chemical logic:
![Page 11: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/11.jpg)
5. Triose Phosphate Isomerase• Near equilibrium; Catalytic perfection• Chemical logic:
![Page 12: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/12.jpg)
6. Glyceraldehyde-3-P DH• Redox and dehydrogenases• Chemical logic purpose
![Page 13: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/13.jpg)
Uncoupled Reaction
![Page 14: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/14.jpg)
Coupled Reaction
• Coupled through covalent catalysis
• Potential conserved in high energy thioester
• Still slightly uphill reaction…
![Page 15: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/15.jpg)
GAPDH Mechanism
![Page 16: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/16.jpg)
7. Phosphoglycerate Kinase • Substrate level phosphorylation• Phosphoryl group transfer• Coupled to reaction 6
![Page 17: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/17.jpg)
Coupled Reactions
• GAPDH: DGo’ = 6.3 kJ/mol• PG Kinase: DGo’ = -18.8 kJ/mol• Overall:
![Page 18: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/18.jpg)
Reactions 8-10
![Page 19: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/19.jpg)
Thermodynamics
![Page 20: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/20.jpg)
Overall Energetics
• Standard Free energies are up and down
• Free energies under cellular conditions are downhill – Three irreversible
![Page 21: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/21.jpg)
Fate of Pyruvate
Aerobic Energy
Anaerobic inmicroorganisms
Anaerobic inhigher organisms
Gluconeogenesis
Amino acidand nitrogenmetabolism
![Page 22: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/22.jpg)
The Problem of Anaerobic Metabolism
• With oxygen, the NADH produced in glycolysis is re-oxidized back to NAD+
• NAD+/NADH is a co-substrate which means…• If there is no oxygen, glycolysis will stop
because…• The solution to the problem is to…
![Page 23: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/23.jpg)
The solution in Yeast• Pyruvate is decarboxylated to acetaldehyde• Acetaldehyde transformed to ethanol
• NAD+ is regenerated to be reused in GAPDH
![Page 24: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/24.jpg)
The Solution in Us
• Lactate formation
• Balanced equation
![Page 25: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/25.jpg)
Other sugars enter glycolysis
High fructose diet puts sugars through glycolysis while avoiding major regulation step
Inability to process galactose is rare, but serious, genetic disorder
![Page 26: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/26.jpg)
Regulation Overview
• Irreversible steps– Phosphofructokinase (3)– Hexokinase (1)– Pyruvate kinase (10)
• Tissue dependent– Muscle: regulated mainly by energy charge– Liver: regulated by building blocks, [glucose],
hormones– Isozymes
![Page 27: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/27.jpg)
Allosteric Regulation of PFK-1
• Based on charge state• ATP binding inactivates
PFK• AMP binding blocks
inactivation• Why AMP?
ADP + ADP AMP + ATP
![Page 28: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/28.jpg)
Resting Muscle
• PFK causes G-6-P buildup unless glucose is being stored
• Feedback inhibition• Hexokinase NOT the
committed step– If glycogen storage full,
send glucose back to the liver!
![Page 29: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/29.jpg)
Active Muscle
• Low charge state activates glycolysis
• Feed forward activation to keep flux forward
![Page 30: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/30.jpg)
Liver PFK Regulation• ATP changes not as
important in liver cells• Citrate is inhibitor
– Citrate is synthetic building block
– No need to break down glucose to make precursors—store it!
• F-2,6-bP is activator– Signals full glycogen
storage– Feedforward activation—
store it as fat!
![Page 31: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/31.jpg)
Liver Hexokinase and Glucokinase
• Hexokinase regulated in liver, too– But we cannot send
glucose out of liver cell– Must be picked up even
when liver cell does not need glucose and glycogen storage is full
– Stored as fat
• Glucokinase: isozyme– Unregulated
• Keeps activating glucose even when there is much G-6-P
• If always active, blood sugar would crash.
• How do we avoid depriving brain?
– High Km • Only active at high
[glucose]
![Page 32: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/32.jpg)
Liver Pyruvate Kinase
• Also allosterically controlled
• Also hormonally controlled
• Low blood sugar = glucagon = inhibited glycolysis
• Allows for gluconeogenesis
![Page 33: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/33.jpg)
General Tissue Glucose Transporters
• GLUT 1 & 3: Km below typical blood glucose (4-8 mM)—works constantly to import glucose
• GLUT 4: sent to cell surface by insulin– Increases uptake of
glucose
![Page 34: Glycolysis Chapter 16, Stryer Short Course. Glycolysis Expectations Memorize/learn Figure 16.1 – Know overall reaction and stages – Explain chemical/physiological](https://reader036.vdocuments.us/reader036/viewer/2022062519/5697bfce1a28abf838ca9a52/html5/thumbnails/34.jpg)
Pancreas and Liver Transporters
• High Km: glucose only taken into these tissues when at high concentration
• Glycolysis is sensor for high [glucose] in pancrease– Release of insulin