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Pharm 411/412 > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

What is gluconeogenesis?

A

Its the process of creating glucose from non-carb sources

**Happens in the liver and kidney

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2
Q

Why is the failure of gluconeogenesis usually fatal?

A
  1. in between meals the brain will struggle for glucose
  2. Lactate produced by RBC and muscle will not be recycled lactic acidosis will set in
  3. Excess ammonia wont be removed efficiently
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3
Q

What are the tissues where gluconeogenesis is active and what do they require?

A

The liver is the major
Studies have shown renal cortex of kidney shown to contribute

Must have mitochondria, cytosol and endoplasmic reticulum

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4
Q

What rxn does gluconeogenesis almost the same as?

A

It the reverse of glycolysis
In steps 1 and 2 of glycolysis the enzymes are different and the last step is completely different and replaced by new rxns

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5
Q

Instead of hexokinase what does gluconeogenesis use in its last step?

A

It uses glucose-6-phosphatase to convert glucose-6-phophate into glucose

Happens in endoplasmic reticulum

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6
Q

Instead of phophofructokinase what does gluconeogenesis use?

A

It is fructose-1,6-biphosphatase

This is a highly regulated step

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7
Q

What happens to pyruvate at the start of gluconeogensis?

A

Gluconeogensis starts with pyruvate (two of them) it then uses ATP and CO2 with pyruvate carboxylase to created oxaloacetate (two of them) from there PEP carboxykinase with GTP to create phophoenol pyruate (two of them)

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8
Q

Why are pyruvate carboxylase and PEP carboxykinase required?

A

They are needed to bypass the irreversible pyruvate kinase rxn of glycolysis

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9
Q

Where is pyruvate carboxylase located and how and what does it create?

A

Pyruvate enters the MITOCHONDRIA from the cytosol to produce OXALOACETATE, it accepts one carbon from bicarbonate (CO2) and uses one ATP and biotin (vit B7) as a cofactor

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10
Q

What is the role of Phophoenolpyruvate carboxykinase?

A

It catalyzes the 2nd step of the rxn by simultaneous decarboxylation and phosphorylation of oxaloacetate

**uses GTP which is high energy phosphate group that ends up in the phosphoenol pyruvate (PEP)

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11
Q

Whats a fun fact about biotin?

A

Its vit B7 and it strongly binds with a protein found in egg, avidin. This means that if you eat a lot of raw eggs it can inhibit biotin absorption and lead to biotin deficiency and inhibit gluconeogenesis

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12
Q

Where is the location of gluconeogenesis enzymes?

A

Pyruvate carboxylase is found ONLY in mitochondrial matrix

All other enzymes are found in the cytosol and one is in the ER

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13
Q

Can oxaloacetate cross the mitochondrial membrane?

A

No, it needs help in order to cross the mitochondrial membrane

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14
Q

What are does oxaloacetate become in order to leave the mitochondria?

A

It can leave as Malate or Aspertate

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15
Q

Glucose 6-Phosphatase in an integral protein of that?

A

The endoplasmic reticulum in the liver

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16
Q

What can tissue do to maintain blood glucose in terms of the enzyme they use and in what process?

A

They can use gluconeogensis to main blood glucose

They do this by restricting the expression of glucose 6-phosphatease in liver and renal cortex
**muscle can not do this

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17
Q

What is the role of glucose 6-phosphatase in gluconeogenesis?

A

It does dephosphorylation of glucose 6-phosphate to create glucose which is released into the cell

**without glucose 6-phosphatase, glucose 6-phosphate is trapped in the cell and is either used for glycolysis or incorporated into glycogen

18
Q

What happens during glycogenolysis?

A
  1. Glycogen is very branched with has glucose as its basic monomer
  2. During low energy/hypoglycemic EPINEPHRINE and GLUCAGON triggers glycogenolysys in liver and muscle
  3. The final product of glycogenolysis is glucose 6-phosphate

**glucose 6-phosphate can either go into glycolysis or be converted into glucose to go into the blood to feed other cells

19
Q

What is hepatic glucose production?

A

Its the combo of gluconeogenesis and glycogenolysis together to get glucose

20
Q

Where does gluconeogensis get its carbon source from?

A

Intermediates of the TCA cycle
Propionate
Amino acids

21
Q

At what level do these intermediates enter gluconeogensis?

A

The level of oxaloacetate

*this makes oxaloacetate one of the most important molecules for gluconeogenesis

22
Q

What is the major amino acid contributor of gluconeogensis?

A

Alanine

it can be converted directly to pyruvate

23
Q

What part of triglycerides can enter gluconeogenesis in mammals?

A

Only glycerol

24
Q

Can plants use triglycerides (fat) for gluconeogenesis?

A

Yes, they have a pathway that allows for this

they use fatty acids as the starting material and its important during germination of seedlings before photosynthesis

25
Q

What is the role of gluconeogenesis in the clearance of lactate?

A

Its called the Cori Cycle
RBC get their ATP thro anaerobic glycolysis which produces lactate that they dump into the blood.
The lactate then travels to the liver where it it converted back to glucose thro gluconeogenesis

**when you workout and produce lactate your muscles also use cori cycle

26
Q

What is the role of gluconeogensis in the removal of excess ammonia?

A

Glucose-alanine cycle

Most ammonia comes from breakdown of amino acids (thro deamination which creates NH3)

In cells (muscle) pyruvate traps the excess ammonia and converts it alanine and then its transported to the liver

In the liver alanine is converted back to pyruvate which usually enters gluconeogenesis

27
Q

What is the importance of the glucose-alaine cycle?

A

The conversion of pyruvate to alanine facilitates the removal from the muscles and other tissues

**once its cleared in the liver, the alanine amine group enters the urea cycle in preparation for elimination

28
Q

What is a pyruvate carboxylase deficiency?

A

An inherited disorder that causes lactic acid and ammonia to build up in the blood.
**its a very rare problem world wide but does seem more common in Indian tribes in Canada

29
Q

What is a deficiency in pyruvate carboxylase such a bad thing (what happens if you dont have it)?

A

Alanine and lactate enter gluconeogensis in the liver but with out PC the lactate produced by RBC and ammonia clearance is severely impaired

30
Q

What is the role of AMPK?

A

AMP-activated protein kinase

It is a sensor of energy status , it maintains cellular homeostasis by switching on catabolic pathways and switching off ATP-consuming processes
**adding the phosphate usually turns it on

31
Q

What activates AMPK?

A

High levels of AMP will activate it

32
Q

What are the pathways that AMPK inhibit?

A 
ATP-consuming pathways
So it inhibits
1. gluconeogensis
2. glycogen synthesis
3. Fatty acid and cholesterol
4. Protein synthesis
33
Q

What are the pathways AMPK upregulates?

A

ATP-producing pathways

  1. Glycolysis
  2. Fatty acid oxidation
  3. Glucose uptake thro GLUT 4
34
Q

How is AMPK activation used to combat diabetes?

A

its suggested that diabetics exercise moderately (a walk) rather than starving

This is because starving will lead to glucagon secretion which leads to gluconeogensis and glycogenolysis which inc fasting blood sugar

A prolong brisk walk activates AMPK which has the benefits without increasing fasting blood sugar

35
Q

What are the Type two diabetes drug that block gluconeogensis

A

Beguanides
Phenformin
Metformin

36
Q

How do beguanides inhibit gluconeogenesis?

A

They inhibit hepatic gluconeogenesis by inhibiting pyruvate carboxylase activity *this affects lactate clearance and ammonia clearance

Phenformin was removed from market because it lead to lactic acidosis in diabetic patients

37
Q

What is the role of the hormone insulin?

A

Site of production : B-cells of pancreas
Released in response to: high blood glucose
Effect: Bring blood glucose down
Target: muscle, adipose and liver

38
Q

What is the role of the hormone glucagon?

A

Site of production: a-cells of pancreas
Released in response to: Reduced blood glucose
Effect: bring glucose up
Target organ: liver

39
Q

What is the role of the hormone Epinephrine?

A

Site of production: adrenal medulla
Released in response to: stress
Effect: blood glucose goes up (more glycogenolysis/gluconeogenesis )
Target: Muscle (all cells) *can increase HR and BP

40
Q

What is the role of the hormone Glucocorticoid (cortisol)?

A

Site of production: Adrenal cortex
Released in response to: Reduced blood glucose/stress
Effect: glucose goes up
Target: All cells *anti-inflammatory and inc BP

41
Q

What is the role of the growth hormone?

A

site of production: Anterior pituitary
Released in response to: Reduced Blood glucose/stress
Effect: glucose goes up
Target: all cells

Pharm 411/412 (11 decks)

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