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Metabolism & Nutrition > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

What tissues are dependent on glucose for continuous supply of energy ?

A

Brain
Erythrocytes
Testes
Kidney medulla
Skeletal muscles under anaerobic conditions

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2
Q

Major substrate for gluconeogenesis

A

Propionate from odd chain FA

Proprionate: propionyl coa + acetyl-CoA
Proprionate is gluconeogenic.

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3
Q

Process that clears lactate produced by muscles and erythrocytes and glycerol produced by adipose tissue ?

A

Gluconeogenesis

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4
Q

Glycogen reserves last for how long before depleted and gluconeogenesis needs to occur ?

A

10-18 hours

Defects in gluconeogenesis can cause hypoglycemia.

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5
Q

Major substrates/precursors for gluconeogenesis ?

A

Lactate
Pyruvate
Glucogenic AA
Propionate (remaining 2 C of the FA)
Glycerol (TG)

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6
Q

Gluconeogenesis occurs in which part of the cell and in what organs ?

A

Cytosol of the cell
Liver (mainly) and approx 10% in the kidney

**During prolonged fasting, the kidneys become major glucose producing organs, contributing to approx 40% of total glucose production.

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7
Q

These 3 irriversible steps of glycolysis are bypassed by alternate enzymes specific to gluconeogenesis :

A

Hexokinase
PFK-1
Pyruvate kinase

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8
Q

Pyruvate converts to what in case of activation of gluconeogenesis ?

A

Oxaloacetate

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9
Q

Pyruvate to oxaloactetate catalyzed by what enzyme ?

A

Pyruvate carboxylase

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10
Q

What enzyme regulates gluconeogenesis and requires Acetyl-CoA for its activity ?

A

Pyruvate carboxylase

Fructose 1,6-bisphosphatase is also regulatory.

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11
Q

Pyruvate carboxylase depends on what to catalyze conversion of pyruvate to oxaloacetate in the presence of ATP & CO2 ?

A

Biotin

Biotin is a cofactor responsible for carbon dioxide transfer in several carboxylase enzymes. Raw egg whites contains avidin which binds to biotin and prevents its absorption.

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12
Q

2 fates of oxaloacetate ?

A
  1. substrate for gluconeogenesis
  2. replenish TCA cycle with oxaloacetate
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13
Q

Where is oxaloacetate synthesized ?

A

Mitochondrial matrix

It has to be transported to the cytosol to be used in gluconeogenesis where the rest of the pathway occurs. Due to impermeability of the membrane, oxaloacetate cannot diffuse and must be converted to malate and then transported to the cytosol where malate can be converted back to oxaloacetate for gluconeogenesis.

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14
Q

GTP used in what reaction of gluconeogenesis ?

A

Phosphoenolpyruvate carboxykinase

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15
Q

2 enzymes involved in the conversion of pyruvate to phosphoenolpyruvtate

A

Pyruvate carboxylase in the mitochondria (pyruvate –> oxaloacetate)

Phosphoenolpyruvate carboxykinase in the cytosol (oxaloacetate –> phosphoenolpyruvate).

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16
Q

**Pyruvate carboxylase is allosterically activated by :

A

Elevated levels of Acetyl-CoA in the mitochondria.

For instance during fasting state

Fasting –> Glucogon –> Fat breakdown –> Acetyl CoA
High amount of Acetyl CoA if someone is fasting.

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17
Q

Acetyl CoA is an allosteric inhibitor for:

A

Pyruvate dehydrogenase

You wanna go in the oxaloacetate direction, not go back and make more acetyl coa.

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18
Q

What enzyme is present in both mito and cytosol and responsible for reversible conversion of malate and oxaloacetate?

A

Malate dehydrogenase

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19
Q

Fructose 1,6 bisphosphatase

A

Fructose 1,6 bisphosphate to fructose-6-phosphate

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20
Q

What enzyme revereses the action of Hexokinase

A

Glucose 6 phosphatase
(Catalyses the conversion of glucose-6-phosphate to glucose)

Glucose is no longer traped

The presence or absence of this enzyme in a tissue determines if the tissue can contribue to maintenance of blood glucose or not.
Absent in the muscle * do not contribute to blood glucose maintenance.
Liver and kidney have this enzyme in order to release free glucose.

21
Q

Glucose-6-phosphatase is located in what specific organelle?

A

Endoplasmic reticulum

22
Q

The ATP required for gluconeogenesis is supplied by the oxidation of:

A

Fatty acids

23
Q

Pyruvate –> oxaloacetate

A

Pyruvate carboxylase

Using biotin as a cofactor

24
Q

Oxaloacetate –> phosphoenolpyruvate :

A

Phosphoenolpyruvate carboxykinase

Using GTP

25
Q

Acetyl-CoA is an allosteric inactivator of what enzyme :

Acetyl CoA produced in max amount during fasting

A

Pyruvate dehydrogenase complexe

26
Q

2 situations when we make Acetyl CoA

A

Glucose influx, converting Pyruvate to Acetyl-CoA
but also when fasting via gluconeogenesis (fasting will break down TG, forming FA that can form Acetyl-CoA)

27
Q

Acetyl-CoA is an allosteric activator of what enzyme

A

Pyruvate carboxylase

Forced oxaloacetate production patwhay (add image)

28
Q

To bypass PFK-1, what enzyme is used ?

A

Fructose 1,6 bisphosphatase

Fructose 1,6-bisphosphate to fructose 6-phosphate

29
Q

What are anapleurotic reactions?

A

Things can come out and get back in the cycle.
‘‘filling up reactions’’

30
Q

Gluconeogenesis from glycerol requires conversion of glycerol to glycerol-3-phosphate. What enzyme catalyzes this reaction ?

A

Glycerokinase

31
Q

Gluconeogenesis is an expansive process, how many ATP and NADH are required ?

A

Requires 6 ATP
2 NADH

FA oxidation is the only one that can fuel the expansive process of gluconeogenesis.

32
Q

For the conversion of propionate to succinyl CoA

A

Biotin
B12

33
Q

What enzymes is lacking in muscles that explains why its cant make its own glucose?

Why we cant convert lactate back to glucose.

A

Glucose 6 phosphatase

34
Q

How is lactate cleared from muscle ?

Cori cycle

A

Via gluconeogenesis

Lactate

35
Q

Pyruvate carboxylase is active in the :

A

Phosphorylated state

Under influence of glucagon

36
Q

Gluconeogenetic enymes are active in

Under influence of Glugacon

A

Phosphorylated state

37
Q

Glycolytic enymes are activated in :

Under influence of Insulin

A

DEphosphorylated state

38
Q

Inuslin activates enzymes of :

A

Glycolysis and deactivate enzymes of gluconeogensis

39
Q

Glucagon will increased activity of

A

Gluconeogenesis and shuts of glycolysis

40
Q

Glucagon increases transcripotion of the gene for whayt enzyme

A

PEP carboxykinase

*Insulin will turn that gene off

41
Q

Acetyl CoA will accumulate in case of fasting which will activate pyruvate carboxylase. Acetyl CoA will inhibit ?

A

PDH complex

42
Q

Acetyl CoA will activate

A

PYRUVATE CARBOXYLASE

inhibits PDH complex because we already have Acetyl-CoA.

43
Q

PFK-1 (glycolysis) is activated by what hormone ?

A

Insulin

44
Q

PFK-1 (glycolysis) is inhibited by what hormone?

A

Glucagon

45
Q

Under the influence of insulin, PFK-2 is activated wich will catalyze what reaction ?

A

Fructose-6-phosphate –> fructose 2,6 bisphosphate

Fructose bisphosphate is an intermediate of gluconeogenesis that will activate PFK-1! Links the 2 pathways.

46
Q

fructose 2,6 bisphosphate activates

Under influence of insulin

A

PFK-1 (glycolytic pathway)

47
Q

Under the influence of glucagon, fructose 2,6 bisphosphate is converted back to fructose 6 phosphate via what enzyme :

A

fructose 1,6 bisphosphatase

Side of gluconeogenesis
add image

48
Q

fructose 1,6 bisph is an intermediate of the glycolysis
fructose 2,6 bisphosphate is a regulator

A

insulin has direct control on PFK2 and indirect control on PFK1

49
Q

fructose 2,6 bisphosphate

A

Metabolism & Nutrition (9 decks)

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