Lecture 17: Carbohydrates, Gluconeogenesis, And Glycolysis Flashcards

1
Q

Be able to recognize the shape of sucrose and lactose

A

Sucrose: Alpha1-Beta2 link between (hexagonal Glucose) and (pentagonal fructose)

Lactose: Beta1-Alpha4 link between (hexagonal Galactose) and (hexagonal glucose)

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2
Q

Define Glyclysis

A

Sequence of reactions that metabolizes one molecule of glucose to Two molecules of pyruvate and generates the net production of two molecules of ATP

  1. This is an anaerobic process (no O2)
  2. Pyruvate can be completely oxidized under aerobic conditions, generating much more ATP
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3
Q

How does ATP usage relate to oxygen content?

A

Glucose metabolism can generate the ATP to power muscle contraction. During a sprint, when the ATP needs to outpace oxygen delivery, as would be the case for Bolt, glucose is metabolized to lactate. When oxygen delivery is adequate, glucose is metabolized more efficiently to carbon dioxide and water.

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4
Q

Describe the possible fates for glucose

A
  • Glucose is a common and important fuel. In mammals, glucose is the only fuel that the brain uses under nonstarvation conditions and the only fuel that red blood cells can use at all.
  • Pyruvate and lactate can be salvaged by being resynthesized to glucose in the metabolic process of gluconeogenesis
  • Sources of glucose in diet: Starch, Glycogen, Disaccharides, especially sucrose and lactose
  • Complete oxidation is obviously more efficient than anaerobic glycolysis
  • See Slide 15
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5
Q

What are the 4 GLUTs?

A
  • GLUT1 – ubiquitous but high in RBCs and brain –High affinity
  • GLUT2 – The main transporter in liver –Low affinity with no regulation
  • GLUT3 – The main transporter in neurons
  • GLUT4 – Skeletal muscle, heart, adipose - Insulin dependent
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6
Q

Where does glycolysis mostly take place?

A

In the cytosol of eukaryotic cells

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7
Q

Describe the First Stage of Glycolysis.

A

1: Glucose
1. 5: Add Hexokinase, and (ATP->ADP) =
2: G-6-P
2. 5: Add Phosphoglucose Isomerase =
3: Fructose 6-phosphate
3. 5: Add phosphofructokinase and (ATP->ADP) =
4. Fructose 1-6 Biphosphate

  • Note: Anywhere that uses ATP is irreversible.
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8
Q

Describe Stage 2 of the glycolysis process

A
  1. Fructose 1-6 Biphosphate
    1. Add Aldolase =
  2. Dihydroxyacetone phosphate and Glyceraldehye 3-phosphate.
    1. The previous components can be converted to each other with Triose Phosphate Isomerase.
    1. Take Glyceraldehyde 3-phosphate and add Glyceraldehyde 3-Phosphate Isomerase and (Pi + NAD+ -> NADH) =
  3. 1-3 Biphosphoglycerate

The fifth step is actually a part of Stage 3.

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9
Q

Describe stage 3 of glycolysis

A

All of these technically occur twice per one unit of glucose.

  1. 1-3 Biphosphoglycerate
    1. Add Phosphoglycerate kinase and (ADP -> ATP) =
  2. 3-phosphoglycerate
    1. Add Phosphoglycerate Mutase =
  3. 2-Phosphoglycerate
    1. Add Enolase (water molecule lost) =
  4. Phosphoenolpyruvate
    1. Add Pyruvate Kinase and (ADP -> ATP)
  5. Pyruvate

Note: Only step 9 (or 9.5 as I have it here) is irreversible in stage 3.

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10
Q

Describe the purposes behind stage 1 of glycolysis

A

Stage 1- trapping and preparation phase

  • No ATP is generated in this stage. 2 are actually consumed
  • Conversion of glucose into fructose 1,6-bisphosphate
  • Consists of three steps: a phosphorylation, an isomerization, and a second phosphorylation reaction.
  • The strategy of these initial steps in glycolysis is to trap the glucose in the cell and form a compound that can be readily cleaved into 2 phosphorylated three-carbon units.
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11
Q

Which steps in Stage 1 of glycolysis are irreversible?

What are inhibitors and activators of each step?

A
  • Glucokinase in liver is used in the place of Hexokinase (which is used in all other tisses)
  • Steps 1 and 3 are irreversible
    Reaction 1: G-6-P inhibits, G-fructose-1-6 P activates this step (but only when glucokinase is used)
    Reaction 3: AMP and Fructose 2,6 BP activates, ATP and Citrate inhibit this step
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12
Q

Describe the purpose behind stage 2 of glycolysis

A

Stage 2 – cleavage and isomerization phase

  • Fructose 1,6-bisphosphate into two three-carbon fragments
  • Aldolase reaction
  • These resulting three-carbon units are readily interconvertible
  • DHAP and GAP
  • Essentially get 2 molecules of GAP
  • Metabolism of GAP pulls in that direction
  • When there’s high energy (high ATP, high NAD+ and low NADH) DHAP in favored and is converted to glycerol 3-phosphate – triacylglycerols - FAT
  • In words, a 6-carbon carbohydrate is split into two 3-carbon molecules. Isomerization of DHAP into G3P, therefore 2 G3P are used in subsequent reactions.
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13
Q

Describe the purpose of stage 3 of glycolysis

A
  • GAPDH step
  • Oxidative phosphorylation of GAP to form 1,3-BPG (and reduce NAD+ to NADH)
  • 1,3-BPG has high phosphoryl- transfer potential
  • NADH contains a pair of “high energy” electrons
  • OXPHOS
  • Phosphoglycerate kinase/mutase step
  • ADP is phosphorylated ATP to form 3-PG
  • Via substrate transfer
  • 2X
  • Phosphate moves to 2 position (2-PG)
  • Enolase/Pyruvate kinase step
  • Dehydration of 2-PG forms PEP, an enol with high phosphoryl-transfer potential (unstable)
  • Then, Pyruvate kinase
  • Phosphoryl group is donated to ADP to form ATP
  • PEP is converted from unstable enol to pyruvate, a stable ketone
  • This step is irreversible
  • Remember = 2X
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14
Q

What becomes of the pyruvate at the end of the glycolysis cycle?

What steps are “officially” the irreversible steps in glycolysis?

A
  • Aerobic – pyruvate to TCA cycle
  • Anaerobic – Step 11 - lactate

Irreversible steps: 1, 3, and 10

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15
Q

The glycolysis cycle doesn’t always have to start with glucose. What other disaccharides can be used?

A
  • Sucrose is a disaccharide of glucose and fructose
  • Lactose is a disaccharide of glucose and galactose
  • Fructose and galactose are converted into glycolytic intermediates
  • Fructose quickly turned to fat in times of high energy
  • See Slide 27
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16
Q

Describe the regulation of glycolysis in the liver

A

In liver—in response to biochemical diversity and need

  • Phosphofructokinase
  • Activated by F-2,6-BP
  • Inhibited by citrate
  • Glucokinase
  • No hexokinase in liver
  • Glucokinase is not inhibited by glucose 6-phosphate – Glucose permanently trapped
  • Pyruvate kinase is regulated by allosteric effectors and covalent modification
17
Q

Describe the 3 fates of pyruvate

A
  • Pyruvate can be reduced to lactate, with the regeneration of NAD+
  • Pyruvate can be oxidized aerobically via the citric acid cycle after first undergoing an oxidative decarboxylation to form acetyl CoA
  • Yeast and some other microorganisms can convert pyruvate to ethanol – maintain redox balance
18
Q

Why is gluconeogenesis necessary?

A
  • Daily glucose requirement of the brain about 120 g
  • Whole body needs 160 g
  • Glucose present in body fluids is about 20 g
  • Glucose readily available from glycogen is approximately 190 g
  • Thus, the direct glucose reserves are sufficient to meet glucose needs for about a day.
  • Gluconeogenesis is especially important during a longer period of fasting or starvation
19
Q

Describe Gluconeogenesis

A
  • Synthesis of glucose from noncarbohydrate precursors
  • Major precursors are lactate, amino acids, and glycerol (but not fatty acids)
  • Pathway converts pyruvate into glucose
  • Pathway is not a reversal of glycolysis

The normal enzymes used during the irreversible steps of glycolysis are (in the liver):
- Glucokinase, Phosphofructokinase, Pyruvate kinase

20
Q

What are the 4 enzymes used instead of the irreversible enzymes to bypass the reverse reaction of glycolysis. (Gluconeogenesis). Where are their respective steps in the reaction?

A

Gluconeogenesis “bypasses” the irreversible steps of glycolysis through the use of four enzymes not present in the glycolytic pathway (in pink)

  • Pyruvate carboxylase (at step “10” (ATP->ADP))
  • Phosphoenolpyruvate carboxykinase (at step “9” (GTP->GDP))
  • Fructose 1,6-bisphosphatase (at step “3”)
  • Glucose 6-phosphatase (At step “1”)

Reminder: 2 pyruvate are needed to synthesize 1 Glucose.

21
Q

Slide 46 makes logical sense, but I recommend you SAT

A

SAT. Stare till your eye melts off.

22
Q

How are glucose pathways regulated in the liver?

A
  • In the liver, rates of glycolysis and gluconeogenesis are adjusted to maintain normal blood glucose levels
  • Fructose 2,6-bisphosphate strongly stimulates phosphofructokinase and inhibits fructose 1,6-bisphosphatase
  • Two enzymes regulate the concentration of fructose 2,6-bisphosphate: phosphofructokinase 2 (PFK2) and fructose bisphosphatase 2 (FBPase2)
23
Q

Briefly describe the Cori Cycle

A
  • Lactate produced in skeletal muscle and red blood cells can be converted back to pyruvate in the liver
  • The pyruvate can enter the gluconeogenic pathway and regenerate glucose (which was the source of the lactate)
  • See Slide 49