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Carbohydrates > Metabolism of Glucose > Flashcards

Metabolism of Glucose Flashcards

1
Q

Major pathways of glucose utilization (4)

A
  1. Storage –> glycogen, starch, sucrose
  2. Oxidation via glycolysis –> pyruvate
  3. Oxidation via pentose phosphate pathway –> ribose- 5- phosphate
  4. Synthesis of structural polymers –> extracellular matrix and cell wall polysaccharides
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2
Q

Glucose transport into cells

A

Glucose cannot diffuse into cells, but enters by one of 2 transports mechanisms:

1) Na+ independent, facilitated diffusion transport system
2) Na+ monosaccharide cotransporter system

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3
Q

Na+ independent facilitated diffusion transport

A
  • This system is mediated by a family of 14 glucose transporters in cell membrane (GLUT-1 to GLUT-14)
  • extracellular glucose binds to the transporter, which then alters its conformation, transporting glucose across the cell membrane
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4
Q

Transporters (5)

-name, expressed in, function

A

GLUT1 –> most tissues, function: basal glucose uptake
GLUT2 –> liver, intestine, pancreatic β cells, function: high- capacity glucose uptake
GLUT3 –> brain, function: neuronal glucose uptake
GLUT4 –> muscle, adipose tissue, heart, function: insulin- dependent glucose uptake
GLUT5 –> small intestine, testis, function: fructose- transporter

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5
Q

Na+ monosaccharide co-transporter system (4)

A
  • energy- requiring process that transports glucose “against” a concentration gradient
  • carrier-mediated process in which the movement of glucose is coupled to the concentration gradient of Na+
  • carrier is sodium- dependent glucose transporter
  • occurs in epithelial cells of the intestine, renal tubules and choroid plexus
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6
Q

Glycolysis (5)

A
  • almost in every living cell
  • anaerobic process
  • glucose molecule is split and converted to 2 pyruvate
  • in anaerobic conditions –> pyruvate may be converted to waste products (ethanol, acetic acid…)
  • in aerobic conditions –> pyruvate is completely oxidized (CO2 and H2O)
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7
Q

Phases of Glycolysis (2)

-just names

A
  • Preparatory phase

- Payoff phase

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8
Q

Preparatory phase (4)

A
  • stage 1,2,3,4,5
  • glucose is phosphorylated twice and cleaved to form two molecules of glyceraldehyde-3-phosphate
  • 2 ATP molecules are consumed
  • This stage creates the actual substrates for oxidation in a form that is trapped inside the cell.
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9
Q

Payoff phase (4)

A
  • stage 6,7,8,9,10
  • glyceraldehyde-3-phosphate is converted to pyruvate
  • 4 ATP and 2 NADH molecules are produced
  • Because two ATP were consumed in stage 1, the net production of ATP per glucose molecule is 2
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10
Q

Write down the summarized equation of Glycolysis

A

Do it again

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11
Q

Step 1 of Glycolysis (6)

A
  • synthesis of glucose- 6- phosphate
  • glucose is phosphorylation
  • phosphorylation prevents the transport of glucose out of the cell
  • requires ATP (ATP –> ADP)
  • irreversible
  • hexokinase catalyzes the process
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12
Q

Step 2 of Glycolysis (4)

A
  • conversion of glucose-6-phosphate to fructose-6-phosphate
  • aldose glucose-6-phosphate is converted to ketose fructose- 6- phosphate
  • phosphoglucose isomerase
  • reversible
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13
Q

Step 3 of Glycolysis (5)

A
  • phosphorylation of fructose-6-phosphate
  • form Fructose- 1,6- bisphosphate
  • +ATP –> ADP
  • phosphofructokinase-1 (PFK-1)
  • irreversible
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14
Q

Investing a second molecule of ATP (in step 3) serves several purposes: (3)

A

1) because ATP is used as the phosphorylating agent, the reaction proceeds with a large decrease in free energy.
2) After fructose-1,6- bisphosphate has been synthesized, the cell is committed to glycolysis
3) Purpose of phosphorylation is to prevent any later product from diffusing out of the cell because charged molecules CANNOT easily cross membranes

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15
Q

Stage 4 of Glycolysis (4)

A
  • cleavage of fructose-1,6- biphosphate into glyceraldehyde-3-phosphate (ketone) and dihydroxyacetone phosphate (aldose)
  • aldol cleavage by enzyme aldolase
  • reversible
  • thermodynamically unfavorable, the reaction proceeds because the products are rapidly removed
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16
Q

Stage 5 of Glycolysis (4)

A
  • interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate
  • triose phosphate isomerase catalyzes the conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate
  • ketose –> aldose
  • reversible
17
Q

Stage 6 of Glycolysis (5)

A
  • oxidation of glycerealdehyde-3-phosphate
  • glycerealdehyde-3-phosphate undergoes oxidation and phosphorylation
  • the product –> 1,3-bisphosphoglycerate, contains high-energy phosphoro-anhydride bond, which may be used in the next reaction to generate ATP
  • enzyme: glyceraldehyde-3-phosphate dehydrogenase
  • NAD+ –> NADH + H+
18
Q

Stage 7 of Glycolysis (5)

A

-phosphoryl group transfer
-substrate - level phosphorylation
-because synthesis of ATP is endergonic, it required an energy source –> ATP is produced
-enzyme: phosphoglycerate kinase
-1,3-Bisphosphoglycerate is converted to
3-Phosphoglycerate

19
Q

Stage 8 of Glycolysis (4)

A
  • interconversion of 3- phosphoglycerate and 2-phosphoglycerate
  • enzyme: phosphoglycerate mutase
  • 3- phosphoglycerate –> 2-phosphoglycerate
  • 3 phosphoglycerate has a low phosphoryl group transfer potential so it is a poor candidate for further ATP synthesis
20
Q

Stage 9 of Glycolysis (4)

A
  • dehydration of 2- phosphoglycerate
  • enzyme: enolase
  • enolase catalyzes the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate (PEP)
  • dehydration increases the phosphoryl transfer potential of the molecule
21
Q

Stage 10 of Glycolysis (5)

A
  • synthesis of pyruvate
  • 2 ATP are formed for each molecule of glucose
  • irreversible
  • Phosphoenolpyruvate + ADP –> Pyruvate + ATP
  • pyruvate kinase
22
Q

In terms of energy, the result of Glycolysis is the production of:

A

-2 ATP and 2 NADH per molecule of glucose

Pyruvate, is an energy-rich molecule and whether or not further energy can be produced, depends on the cell type and the availability of O2.

23
Q

Pyruvate

-under aerobic conditions:

A

Pyruvate –> acetly Co-A –> TCA cycle –> 2 acetly carbons oxidized to form CO2 and NADH + FADH2 –> electron transport chain transfer electrons from NADH and FADH2 to form O2 and water –> energy released during ETC synthesizes ATP

TOTAL: 32 ATP

24
Q

Regulation of Glycolysis

-rate at which the glycolytic pathway operates in a cell is controlled by…. (3)

A
  • Kinetic properties of its hexokinases isoenzymes
  • Allosteric regulation of the enzymes that catalyze the 3 irreversible reactions (1,3,10)

enzymes: hexokinase, phosphofructokinase-1 (PFK-1), pyruvate kinase

25
Q

Hexokinases (4)

A
  • four isoenzymes (I-IV)
  • hexokinase I –> liver / hexokinases I,II,III –> other body tissues
  • inhibited by: glucose- 6- phosphate and glucagon
  • stimulated by glucose and insulin
26
Q

Glucokinase (6)

A
  • = hexokinase IV, has different kinetic properties but catalyzes the same reaction
  • liver, pancreas, intestine, brain
  • requires much higher glucose concentrations for optimal activity
  • NOT INHIBITED by glucose-6-phosphate
  • inhibited by fructose-6-phosphate, glucagon
  • stimulated by insulin and glucose
27
Q

Allosteric regulation

A

-on irreversible reactions = reactions catalyzed by hexokinases I,II,III, PFK-1 and pyruvate kinase

28
Q

Pyruvate kinase

-allosteric effectors –> activators and inhibitors

A

activators –> high adenosine monophosphate (AMP), accumulated fructose-1,6-bisphosphate
inhibitors –> high ATP and Acetyl CoA

29
Q

Phosphofructokinase-1 (PFK-1)

-allosteric effectors –> activators and inhibitors

A

activators –> adenosine monophosphate (AMP) and fructose-2,6- biphosphate
inhibitors –> high levels of ATP and citrate

30
Q

Phosphofructokinase-2 (PFK-2) (3)

A
  • bifunctional enzyme
  • behaves as phosphatase when phosphorylated in response to the hormone glucagon
  • functions as kinase when dephosphorylated in response to the hormone insulin
31
Q

Hormonal regulation

-Glycolysis is also regulated by which hormones

A

Peptide hormones

  • glucagon
  • insulin
32
Q

Glucagon (4)

A
  • released by pancreatic α-cell when blood glucose is LOW
  • activates phosphatase function of PFK-2, reducing the level of fructose- 2,6- bisphosphate in the cell
  • decreases PFK-1 activity
  • in liver –> glucagon also inactivates pyruvate kinase by phosphorylating it
33
Q

cAMP (3)

A
  • synthesized from ATP by adenylate cyclase
  • cAMP binds to and activates protein kinase A (PKA)
  • PKA the initiates a signal cascade of phospho/dephosphorylation reactions that alter the activities of enzymes and transcription factors
34
Q

Insulin

A
  • released from pancreatic β-cells when blood glucose levels are high
  • activates the kinase function of PFK-2 –> increases the levels of fructose-2,6- bisphosphate in the cell, increasing glycolytic flux
35
Q

LOOK AT SLIDE 33

VERY IMP

A

VERY VERY IMP

36
Q

What determines the final amount of ATP from the complete oxidation of one molecule of glucose?

A

It depends on the method used to transport cytoplasmic NADH (formed on glycolysis) into mitochondria.

  • glycerol phosphate shuttle –> FADH 2nd complex of TCA cycle = 1.5 ATP
  • malate aspartate shuttle –> NADH 1st complex of TCA cycle = 2.5 ATP

type of shuttle depends on the type of tissue

Carbohydrates (4 decks)

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