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Year 1 NME > Regulation of Carbohydrate Metabolism > Flashcards

Regulation of Carbohydrate Metabolism Flashcards

1
Q

What is phosphofructokinase?

A
  • catalyses for the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate
  • a key regulatory step in the glycolytic pathway
  • the committed step in glycolysis
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2
Q

What is pyruvate kinase and why is it important?

A
  • enzyme that converts phosphoenolpyruvate to pyruvate
  • pyruvate can then enter the citric acid cycle
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3
Q

Regulation of glycolysis is dependent on glucose entry into the cell. What are the other 2 key enzymes that are part of the glycolysis pathway within cells that regulate glycolysis?

A

1 - Phosphofructoskinase-1 - commited step in glycolysis

2 - Pyruvate kinase

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4
Q

What is glycogenolysis and glycogenesis?

A
  • glycogenolysis = breakdown of glycogen (creates energy)
  • glycogenesis = storing glucose (requires energy)
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5
Q

Hormonal (adrenalin/glucoagon) and allosteric bindng can do what to glycogenesis and glycogenolysis?

A
  • regulate the level of each
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6
Q

In the glycolysis what are the 3 irreverisble steps?

A

1 - hexokinase/glucokinase

2 - phosphofructokinase-1 (PFK-1)

3 - pyruvate kinase

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7
Q

What is gluconeogenesis?

A
  • the metabolic process by which organisms produce sugars (namely glucose) for catabolic reactions from non-carbohydrate precursors
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8
Q

What are the 3 main substrates that are used for de novo glucose synthesis, commonly referred to as gluconeogenesis?

A
  • lactate from glycolysis
  • amino acids from protein breakdown
  • glycerol (but NOT fatty acids) from fat metabolism
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9
Q

Where are the 2 places where de novo glucose synthesis, commonly referred to as gluconeogenesis occurs in the body?

A

1 - liver

2 - kidneys

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10
Q

When is gluconeogenesis most important?

A
  • during fasting or starvation state
  • maintains blood glucose and preserve glucose-dependent cerebral function and red blood cell metabolism
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11
Q

Hexokinase, PFK-1 and pyruvate kinase are the 3 irreversible reactions of glycolysis. In terms of Gibbs Free Energy change (_/_G), are these reactions sponatenous or do they require energy?

A
  • spontaneous
  • have a high negative free energy (_/_G)\
  • essentially means reversing is energetically unfavourable
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12
Q

There are 4 bypass reactions in gluconeogensis that are spontaneous, meaning they have a high negative free energy (_/_G) and can overcome the 3 irreversible reactions of glycolysis, namely hexokinase, PFK-1 and pyruvate kinase. What are the 4 bypass reactions of gluconeogenesis?

A

1 - Glucose 6-phosphatase

2 - Fructose 1,6-bisphosphatase-1

3 - Phosphoenolpyruvate carboxykinase

4 - Pyruvate Carboxylase

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13
Q

Glucose 6-phosphatase is one of the bypass reactions of gluconeogenesis. What does this enzyme do?

A
  • removes phosphate from Glucose 6-phosphate
  • produces glucose that can be released into the blood
  • final step of gluconeogenesis
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14
Q

Fructose 1,6-bisphosphatase is one of the bypass reactions of gluconeogenesis. What does this enzyme do?

A
  • removes a phosphate from fructose1,6-bisphosphate (FBP)
  • creates fructose 6 phosphate
  • fructose1,6-bisphosphate (FBP) would normally form 2 3 carbon moleucles of glyceraldehyde-3-phosphate (G-3-P)
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15
Q

Gluconeogenesis requires energy, where does this energy come from?

A
  • fatty acids
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16
Q

Gluconeogenesis requires carbon backbones to create energy, where do these backbones come from?

A
  • lactate
  • amino acids
  • glycerol
17
Q

Pyruvate Carboxylase is one of the bypass reactions of gluconeogenesis. What does this enzyme do?

A
  • carboxylation of pyruvate to oxaloacetate (adding a carboxyl group)
  • this is irreversible and occurs prior to citric acid cycle
18
Q

Phosphoenolpyruvate carboxylase is one of the bypass reactions of gluconeogenesis. What does this enzyme do?

A
  • carboxylation of oxaloacetate to phosphoenolpyruvate
  • this is the product prior to pyruvate
19
Q

The regulation of glycolysis is through phosphofructokinase-1 (PFK-1), which is the commited step in glycolysis responsible for adding a phosphate group to fructose-6-phosphate (F-6-P) making fructose1,6-bisphosphate (FBP). If there is a lot of ATP in the cell, what does this do to PFK-1 activity and glycolysis?

A
  • allosterically binds to PFK-1 and inhibits activity
  • this reduces glycolysis
20
Q

The regulation of glycolysis is through phosphofructokinase-1 (PFK-1), which is the commited step in glycolysis responsible for adding a phosphate group to fructose-6-phosphate (F-6-P) making fructose1,6-bisphosphate (FBP). If there is a lot of ATP in the cell, ATP can allosterically bind to PFK-1 and inhibit its activity, reducing glycolysis. In addition, this process communicates with glycogen phosphorylase to do what?

A
  • inhibit glycogen phosphorylase
  • glycogen breakdown is reduced
21
Q

The regulation of glycolysis is through phosphofructokinase-1 (PFK-1), which is the commited step in glycolysis responsible for adding a phosphate group to fructose-6-phosphate (F-6-P) making fructose1,6-bisphosphate (FBP). If there is a lot of AMP in the cell, what does this do to the PFK-1 activity?

A
  • AMP is a sign of low ATP
  • AMP alosterically binds to PFK-1 and increases activity
  • increased glycolysis follows
22
Q

The regulation of glycolysis is through phosphofructokinase-1 (PFK-1), which is the commited step in glycolysis responsible for adding a phosphate group to fructose-6-phosphate (F-6-P) making fructose1,6-bisphosphate (FBP). If there is a lot of AMP in the cell, which is a sign of low ATP, AMP can allosterically bind to PFK-1 and increase its activity, increasing glycolysis. In addition, this process communicates with glycogen synthase and glycogen phosphorylase to do what?

A
  • inhibits glycogen synthase
  • activates glycogen phosphorylase
  • glycogen breakdown is increased
23
Q

Phosphofructokinase-1 (PFK-1) can be upregulated by high AMP or down regulated by high ATP, which can increase or decrease glycolysis respectively. What else is able to regulate PFK-1?

A
  • H+ is able to allosterically bind and inhibit PFK-1
  • H+ are generated during anoxia and anabolic muscle contractions due to lactic acid production and reduces pH
  • glycolysis drives pyruvate which can feed into lactic acid production which can be dangerous
24
Q

Phosphofructokinase-1 (PFK-1) can be upregulated by high AMP or down regulated by high ATP, which can increase or decrease glycolysis respectively. H+ is able to allosterically bind and inhibit PFK-1. H+ generations is increased during anoxia and anabolic muscle contractions due to lactic acid production that reduces pH. As glycolysis drives pyruvate production that can feed into lactate and ultimately lactic acid production, H+ therefore inhibits PFK-1 and glycolysis. What organ can overcome this?

A
  • heart
25
Q

Nutrients are also able to activate phosphofructokinase 1 (PFK-1), which is the commited step in glycolysis. What is the most potent allosteric activator of PFK-1 that in turn increases glycolysis?

A
  • Fructose-2,6-bisphosphate
  • made by the body just for regulating PFK-1
26
Q

Nutrients are also able to inhibit phosphofructokinase 1 (PFK-1), which is the commited step in glycolysis. What compound from the citric acid cycle can inhibit PFK-1 that in turn decreases glycolysis?

A
  • citrate
  • if lots of acetyl-CoA entering citric acid cycle in glycolysis then it may overload the system
  • to conserve glucose glycolysis is inhibited
27
Q

Fructose-2,6-bisphosphate is the most potent allosteric activator of PFK-1 and is created by Phosphofructoskinase-2 (PFK-2) purely to activate PFK-1 and increase stimulates glycolysis to allow utilisation for energy production or fat synthesis. However, once created Fructose-2,6-bisphosphate is also able to inhibit fructose-1,6-bisphosphatase that is a bypass step in gluconeogenesis. Why is this important?

A
  • so we can switch off gluconeogenesis
  • focus is on glycolysis
28
Q

In skeletal muscle Fructose 2,6 bisphosphate can be activated by high glucose concentrations, high glycogen breakdown and high levels of AMP (obviously not all at the same time) which in turn activates phosphofructoskinase-1 (PFK-1) and increases glycolysis. However, in the liver does the same process occur?

A
  • no
  • liver uses glycogen and gluconeogenesis to maintain blood glucose
  • glycolysis and fructose 2,6 bisphosphateis are inhibited
29
Q

Fructose 2,6 bisphosphate is able activate phosphofructoskinase-1 (PFK-1), but what happens in the skeletal muscle compared to liver?

A
  • liver = fructose 2,6 bisphosphate and phosphofructoskinase-1 (PFK-1) are inhibited reducing glycolysis
  • skeletal muscle = fructose 2,6 bisphosphate activates phosphofructoskinase-1 (PFK-1) and increases glycolysis
30
Q

Does Fructose-1,6-bisphosphate and Phosphofructoskinase-1 (PFK-1) which are important in glycolysis come under direct control of hormones in the liver?

A
  • no
31
Q

Fructose-1,6-bisphosphate (F-1,6-BPase) and Phosphofructoskinase-1 (PFK-1) are important in glycolysis does come under direct control of hormones in the liver, so how is F-1,6-BPase and PFK-1 regulated in the liver?

A
  • Fructose-2,6-bisphosphate (F-2,6-BP) IS affected by hormones
32
Q

Fructose-1,6-bisphosphate (F-1,6-BPase) and Phosphofructoskinase-1 (PFK-1) are important in glycolysis but do not come under direct control of hormones in the liver, but fructose-2,6-bisphosphate (F-2,6-BP) IS affected by hormones. How do hormones regualte F-2,6-BP?

A
  • if blood glucose is low glucagon is released from alpha cells
  • glucagon binds to receptor on liver
  • cellular cascade initiates gluconeogenesis or glycogen breakdown
33
Q

Fructose-1,6-bisphosphate (F-1,6-BPase) and Phosphofructoskinase-1 (PFK-1) are important in glycolysis but do not come under direct control of hormones in the liver, but fructose-2,6-bisphosphate (F-2,6-BP) IS affected by hormones. Once glucagon has bound to the receptors on the liver what triggers the cellular cascade?

A
  • activation of cAMP which in turn activates AMP-activated protein kinase
  • kinases add phosphates to molecules
34
Q

Once glucagon has bound to the receptors on the liver when blood glucose is low, cAMP is activated which in turn activates AMP-activated protein kinase (AMPPK). AMPPK is a kinase and adds phosphates to molecules. What happens to Phosphofructokinase 2 (PFK-2), which is responsible for creating Fructose-2,6-bisphosphate, which activates PFK-1 increasing glycolysis, when it is phosphorylised by AMPPK in the liver?

A
  • adding a phosphate to PFK-2 inhibits it
  • PFK-2 is an inhibitor of gluconeogenesis and an activator of glycolysis
  • glycolysis = reduced
  • gluconeogenesis = increased
35
Q

Once glucagon has bound to the receptors on the liver when blood glucose is low, cAMP is activated which in turn activates AMP-activated protein kinase (AMPPK). AMPPK is a kinase and adds phosphates to molecules. What happens Fructose-2,6-bisphosphatase, which is responsible for breaking down Fructose-2,6-bisphosphate?

A
  • AMPPK adds a phosphate to Fructose-2,6-bisphosphatase
  • Fructose-2,6-bisphosphatase becomes active and begins to break down Fructose-1,6-bisphosphate
  • glycolysis = reduced
  • gluconeogenesis = increased
36
Q

In the liver what does phosphorylation do to Fructose 2,6-bisphosphatase and Phosphofructokinase 2 (PFK-2)?

A
  • PFK-2 = inhibited (involved in increasing glycolysis)
  • Fructose 2,6-bisphosphatase = activated (involved in gluconeogenesis)
  • both inhibit glycolysis and activate gluconeogenesis
37
Q

What is beta oxidation?

A
  • catabolic process by which fatty acid molecules are broken down in the mitochondria
  • acetyl-CoA and oxaloacetate are created and can then enter the citric acid cycle

Year 1 NME (61 decks)

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