BCEM 393 Lecture Notes - Lecture 11: Glucose Transporter, Hexokinase, Glut4

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Glycolysis and Fermentation
GLUCOSE UPTAKE GLUCOSE TRANSPORTERS
- Transmembrane carrier proteins
- Carrier proteins are involved in facilitated diffusion
- Carrier proteins move molecules down their concentration gradients
- GLUT4 (glucose transporter 4)
- Important to have in blood stream after having a meal because insulin levels are high
- Insulin levels signal the release of GLUT4
GLYCOLYSIS AN OVERVIEW
- Glycolysis is the sequence of reactions that converts one molecule of glucose into two
molecules of pyruvate while generating ATP
- Function is to generate ATP and to provide building blocks for biosynthesis
- Intermediate molecules can function as precursors to other molecules
GLYCOLYSIS
- Common to both prokaryotic and eukaryotic cells
- In eukaryotic cells, glycolysis takes place in the cytoplasm
- Glycolysis can be broken down into 2 main stages:
- Stage 1: Trap and prep
- Traps the glucose in the cell and forms a compound that can be readily cleaved into
phosphorylated 3-carbon units
- Stage 2: Harvest
- ATP is harvested when the #-carbon fragments are oxidized to pyruvate
GLYCOLYSIS OVERVIEW
- 6 carbons enter the pathway as one glucose, 6 carbons exit the pathway as 2 pyruvate
molecules
- Pathway can be divided into prep and payoff phases
- Carbon is split from one 6 carbon unit into 2, 3 carbon units
- At steady state, flux in stage 2 is 2 times greater than flux in stage 1
- 2 ATP are used to prime (start) the pathway, 4 ATP are produced in the end; net is 2
ATP/glucose
- 2 NAD+ are converted to NADH
STAGE 1 PREPARATION
- Point of regulation: Hexokinase inhibited by its product G6P > irreversible step
- Main point of regulation: Phosphofructokinase works as the pacemaker of glycolysis >
irreversible step
- The activities of the points of regulation are regulated by the reversible binding of allosteric
effectors, by covalent modification, or by the regulation of transcription
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HEXOKINASE TRAPS GLUCOSE INSIDE THE CELL
- Dont want too much glucose build up because then glucose cant, or it becomes hard for it
to, enter the cell
- It is phosphorylated by ATP to form G6P by hexokinase
- Requires energy
- Requires Mg2+ for activity (forms a complex with ATP)
- Mg2+ is used to stabilize the charge repulsion in the phosphate group of ATP
- The reaction catalyzed by hexokinase is virtually irreversible and is a site of regulation
- Significance of reaction:
- G6P cannot pass through the cell membrane because it is not a substrate for glucose
transporters
- Ensures glucose does not build up inside the cell so that glucose can continue to move
down its concentration gradient (GLUTs)
- Prepares glucose to become a phosphorylated three-carbon compound with high
phosphoryl-transfer potential > able to destabilize glucose and facilitate the next series of
metabolic steps
PHOSPHOGLUCOSE ISOMERASE CATALYZES THE REVERSIBLE REACTION OF CONVERTING
G6P TO F6P
- Conversion of an aldehyde sugar (aldose) to a ketone sugar (ketose)
- What is the logic behind this reaction?
- Prepares the cell for later glycolytic steps, which metabolize three-carbon molecules sing
G6P is not readily cleaved into two 3-carbon fragments, while F6P is
PHOSPHOFRUCTOKINASE TRAPS THE SUGAR AS THE FRUCTOSE ISOMER
- Fructose 6-phosphate is phosphorylated by ATP to fructose 1,6-bisphosphate (F-1,6-BP)
- Requires energy
- Requires Mg2+ for activity (forms a complex with ATP)
- This reaction is irreversible under cellular conditions
- The major regulatory site for glycolytic flux (ie. pacemaker)
PHOSPHOFRUCTOKINASE IS AN ALLOSTERIC ENZYME
- Recall, that most enzymes follow Michaelis-Menton kinetics
- Not regulated in the cell; activity is governed simply by substrate presence (maximum rate
achieved by the system, at saturating substrate concentration)
- Allosteric enzymes have multiple active sites and distinct regulatory sites that control the flu
of biochemicals through a metabolic pathway
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Document Summary

Carrier proteins are involved in facilitated diffusion. Carrier proteins move molecules down their concentration gradients. Important to have in blood stream after having a meal because insulin levels are high. Insulin levels signal the release of glut4. Glycolysis is the sequence of reactions that converts one molecule of glucose into two molecules of pyruvate while generating atp. Function is to generate atp and to provide building blocks for biosynthesis. Intermediate molecules can function as precursors to other molecules. Common to both prokaryotic and eukaryotic cells. In eukaryotic cells, glycolysis takes place in the cytoplasm. Glycolysis can be broken down into 2 main stages: Traps the glucose in the cell and forms a compound that can be readily cleaved into phosphorylated 3-carbon units. Atp is harvested when the #-carbon fragments are oxidized to pyruvate. 6 carbons enter the pathway as one glucose, 6 carbons exit the pathway as 2 pyruvate molecules. Pathway can be divided into prep and payoff phases.

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