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B2 Biochem > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

Gluconeogenesis

A

A metabolic pathway that results in the generation of glucose from non-carbohydrate precursors

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2
Q

Purpose of GNG

A

To maintain blood glucose levels and avoid hypoglycemia under conditions of fasting (>10-18 h)

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3
Q

Tissues involved in GNG

A

Liver
-predominantly ~90% in overnight fast

Kidney Cortex
~10%
-only during prolonged fasting will it near 40%

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4
Q

Subcellular localization of GNG

A

Mitochondrial matrix - step 1

Cytosol - all reversible steps of glycolysis

ER - last step (dephosphorylation) to produce glucose

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5
Q

Substrates of GNG

A

Glycerol, Amino Acids, Lactate, Acetyl CoA

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6
Q

Glycerol in GNG

A

Released during hydrolysis of TAGs in adipocytes and is delivered by the blood to the liver

Adipocytes lack glycerol kinase

In the liver:
Glycerol -> glycerol-phosphate -> DHAP (glycolic intermediate)

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7
Q

Adipocytes lack _______ _____, which is why it is transferred to the liver.

A

Glycerol kinase

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8
Q

Amino Acids in GNG

A

Major source of AA are derived from tissue protein synthesis

Ala is the major AA used but 18 out of 20 can be used

Most of the AA are converted in the TCA to intermediates that can yield OAA at some point

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9
Q

What is the major AA used in GNG?

A

Alanine

But others can be used

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10
Q

Lactate in GNG

A

Can be converted back into Pyruvate by Lactate Dehydrogenase

Released from cells under anaerobic conditions (RBCs and exercising muscle)

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11
Q

What enzyme converts lactate back into Pyruvate?

A

Lactate dehydrogenase

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12
Q

What does the Cori Cycle do?

A

Converts glucose into lactate (under anaerobic conditions)
Excretes lactate to plasma and then sent to the liver
Lactate is then converted back into Glucose
Released back into circulation (to be possibly repeated)

FORMS A CYCLE YO

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13
Q

Acetyl CoA in GNG

A

Cannot be converted back into Pyruvate in humans

PDH is irreversible and there is NO enzyme for the reverse reaction

Fatty Acids CANNOT serve as a substrate for Gluconeogenesis

FA oxidation provides the liver with the energy requires to perform Gluconeogenesis

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14
Q

How is Acetyl CoA converted back into Pyruvate in humans?

A

It’s not. It can’t. Idiot.

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15
Q

__________ cannot serve as a substrate in Gluconeogenesis.

A

Fatty Acids

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16
Q

____ ____ ________ provides the liver with energy requires for perform GNG.

A

Fatty Acid Oxidation

17
Q

How many reversible and irreversible reactions are in GNG?

A

7 reversible

3 irreversible

11 total

18
Q

Gluconeogenesis is the opposite of….

A

Glycolysis

19
Q

The irreversible steps are due to 4 alternative enzyme in what UNIQUE steps?

A
  1. Pyruvate to OAA
  2. OAA to PEP
  3. F-1,6-bis-P to F-6-P
  4. G-6-P to Glucose
20
Q

Carboxylation of Pyruvate to OAA

A

In the mitochondrial matrix

Provide OAA for GNG and TCA replenishment

Enzyme: Pyruvate Carboxylase

  • Requires biotin as a coenzyme
  • Allosterically activated by Acetyl CoA

OAA cannot be exported, so converted to Malate, then converted to OAA once exported

Enzymes: Malate dehydrogenase and PEP carboxykinase

21
Q

Pyruvate Carboxylase requires _____ as a coenzyme and is allostericall at activated by ______ ___.

A

Biotin, Acetyl CoA

22
Q

The Carboxylation of Pyruvate to OAA takes place in the…

A

Mitochondrial matrix

23
Q

Oxaloacetate is exported to the cytosol by…

A

Due to the lack of transporters for OAA, it is converted to Malate, then transported.

Once in the cytosol, it is converted back into OAA.
-via PEP carboxykinase and Malate dehydrogenase

24
Q

Decarboxylation of cytosol in OAA

A

IRREVERSIBLE

Driven by GTP hydrolysis

Pairing Carboxylation with de-carboxylation makes GNG energetically possible.

Enzyme: PEP-carboxykinase (PEPCK)

25
Q

Dephosphorylation of F-1,6-bisP

A

hydrolysis reaction

Bypasses the irreversible PFK-1 reaction

Important site for regulation

Enzymes: F-1,6-bisphosphatase

  • Inhibitors: AMP (signal energy poor=stop), and allostericall you by F-2,6-bisP
  • Activators: high ATP, low AMP
26
Q

Regulation by fructose-2,6-bisphosphatase (synthesized by PFK-2)

A

inactivates f-1,6-bisP and stops GNG

The common regulator allows tight regulation assuring the pathways of glycolysis and Gluconeogenesis are mutually exclusive

27
Q

Dephosphorylation of GLucose-6-P

A

Hydrolysis reaction

Bypasses the irreversible Hexo/Glucokinase reaction

Provides energetically favorable step to produce glucose

Enzyme: glucose 6-phosphatase

  • also used during Gluconeogenesis to yield free glucose
  • glucose can then be transported out of the liver to maintain blood glucose
28
Q

Summary of GNG

A

endergonic (Energy-requiring), anabolic

For 1 Glucose:
4 ATP used
2 GTP used
2 NADH used

29
Q

Regulation of GNG by glucagon

A

Inhibits PFK-2, lowers f-2,6-bisP inhibiting glycolysis and activated GNG

Inhibits Pyruvate kinase, therefore PEP is used for GNG as opposed to glycolysis

Stimulates transcription of PEPCK, insulin inhibits it

30
Q

Regulation of GNG by substrate availability

A

Protein breakdown in other tissues and subsequent AA release yields gluconeogenic precursors in the liver, which stimulate GNG

ATP and NADH are provided by the oxidation of FAs in the liver

31
Q

Allosteric activation by Acetyl CoA

A

Buildup of Acetyl CoA, signals the diversion of OAA for Gluconeogenesis

Activates Pyruvate Carboxylase

Inhibits PDH, assuring Pyruvate is diverted to the production of glucose and away from the TCA cycle

32
Q

Allosteric inhibition by AMP

A

F-1,6-bisP is inhibited by AMP

PFK-1 is activated by AMP

As with regulation of the two enzymes by F-2,6-bisP, the reciprocal regulation of each of these enzymes by the same Allosteric effector assures the two pathways are mutually exclusive

B2 Biochem (13 decks)

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