ME03 - GLUCONEOGENESIS Flashcards Preview

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Flashcards in ME03 - GLUCONEOGENESIS Deck (18):
1

Synthesis of carbohydrates from non-carbohydrate sources
Such as:
intermediatesofglycolysisandtheTCA
glycerolfromtriacylglycerols
lactatethroughtheCoriCycle carbonskeletons(α ketoacids) of glucogenic amino acids

GLUCONEOGENESIS
“Gluconeogenesis means to make new glucose. “Neogenesis, you’re going to make new memories. It is the reversibility of glycolysis. For you to undo something, you need to put conscious effort with it. Time. Energy.

2

Three non-equilibrium reactions in glycolysis, catalyzed by ______ ,_______ and _______, prevent simple reversal of glycolysis.

hexokinase, phosphofructokinase and pyruvate kinase

3

Glycogen synthesis involves a different pathway via

uridine diphosphate glucose and glycogen synthase

4

Biomedical Importance of Gluconeogenesis

To supply glucose to the following when glycogen
supply has been depleted:
! Brain and erythrocytes
! Contracting skeletal muscles ! Fetus in pregnancy
! Lactating mammarygland
! Retina,lens,renalmedulla

o To clear products of metabolism
! Lactate and glycerol–waste products that are
recycled by the body back to glucose reflecting
cellular economy

5

Where does it occur?

Occurs in the liver (90%) and the kidney (10%)
o During prolonged fasting, the kidneys contribute as
much as 40%
o Occurs in both mitochondria and cytoplasm

6

What is the substrate?

Pyruvate
Glycerol
• Adipocytes cannot phosphorylate glycerol
because they lack glycerol kinase Lactate
• Released from exercising skeletal muscles and cells that lack mitochondria
Propionate
• Precursor of glucose in ruminants, enters
via the citric acid cycle

7

Enzymes involved in Gluconeogenesis

Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase

8

Enzyme during the UNFED STARVING PHASE

Pyruvate carboxylase

Catalyzesthecarboxylationofpyruvateto
oxaloacetate
• ATP-requiring reaction; vitamin biotin as
coenzyme that will bind to CO2
• The resultant oxaloacetate is reduced to
malate, exported from the mitochondrion into the cytosol and there oxidized back to oxaloacetate

9

Decarboxylationandphosphorylationof oxaloacetate to phosphoenolpyruvate

Phosphoenolpyruvate carboxykinase

10

Conversionoffructose1,6-bisphosphateto
fructose 6-phosphate
! Determinescapabilityofsynthesizingglucose
from pyruvate and triose phosphates

Fructose 1,6-bisphosphatase

Liver,kidney,andskeletalmuscle

11

Conversionofglucose6-phosphatetoglucose ! Liverandkidney

Glucose 6-phosphatase

12

Reactions unique to gluconeogenesis

Carboxylation of pyruvate
Transport of oxaloacetate to the cytosol
Decarboxylation of cytosolic oxaloacetate
Dephosphorylation of fructose 1,6-biphosphate
Dephosphorylation of glucose 6-phosphate

13

Transport of oxaloacetate to the cytosol

OAAisunabletodirectlycrosstheinner
mitochondrial membrane
! Mustbereducedfirsttomalatebymitochondrial
malate dehydrogenase
! Malatecanbetransportedfromthemitochondria to the cytosol, where it is reoxidized to oxaloacetate by cytosolic malate dehydrogenase

14

Decarboxylation of cytosolic oxaloacetate

Oxaloacetateisdecarboxylatedand
phosphorylated in the cytosol by PEP-
carboxykinase (PEPCK)
! ReactiondrivenbyhydrolysisofGTP

15

Dephosphorylation of fructose 1,6-biphosphate

Regulationbyfructose2,6-bisphosphate
• Fructose 2,6-bisphosphate inhibits fructose 1,6-bisphoosphatase
• An allosteric modifier whose concentration is influenced by the level of circulating glucagon
• NOTE: Recall that fructose 2,6-bisphosphate activates PFK-1 of glycolysis

16

Only organs that release
free glucose from glucose 6-phosphate

Liver and kidney

17

two enzymes for the Dephosphorylation of glucose 6-phosphate

Glucose 6-phosphate translocase which transports glucose 6-phosphate across the endoplasmic reticular (ER) membrane

Glucose 6-phosphatase found only in gluconeogenic cells which removes the phosphate, producing free glucose
• NOTE: These enzymes are required for the final step in glycogenolysis, as well as gluconeogenesis

18

This is the rate-limiting step of gluconeogenesis

Step 3: Fructose-1,6-BP > Fructose-6-P

Activates phosphofructokinase-1 > favors glycolysis

Inhibits
F-1,6-bisphosphatase > inhibits gluconeogenesis

o Activator: ATP
o Inhibitor: Fructose-2,6-BP and AMP