Carbohydrate Metabolism Flashcards

1
Q

What is the critical blood glucose value?

A

2.5 mM

Below = Hypoglycaemia, causes:

  • Muscle weakness
  • Loss of coordination
  • Mental confusion
  • Sweating
  • Hypoglycaemic coma and death

Above = Hyperglycaemia, causes:

  • Non enzymatic modification of proteins
    • Cataracts
  • Hyperosmolar coma
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2
Q

Why is glucose stored as glycogen?

A

Glucose cannot be stored as it is osmotically active

Glycogen has a branched structure, which means it can be rapidly mobilised

It’s a safe way to store glucose

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3
Q

What is glycogenesis?

A
  • Glycogen synthesis
  • Takes place in liver and skeletal muscle
  • Occurs when blood glucose levels high
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4
Q

What regulates glycogenesis?

A

Insulin

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5
Q

What is G-6-P converted into in glycogenesis?

A

Glucose 1 phosphate by phosphoglucomutase

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6
Q

What is G-1-P converted into?

A

UDP- glucose by UDP-glucose-pyrophosphorylase

Glucose is activated by the reaction with UTP

UTP (uridine triphosphate) is converted into PPI

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7
Q

What does UDP-glucose react with?

A

Glycogenin - this is a protein primer- and this complex catalyses the addition of the first glucose molecule. This then acts as a substrate for glycogen synthase, which is able to bind glucose molecules to glycogenin forming the alpha 1,4 glycosidic bonds.

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8
Q

What is the bond between each glucose molecule attached to glycogenin?

A

Alpha 1-4 glycosidic bond (straight chain)

Alpha 1-6 glycosidic bond (branched chain, this bond causes the branching)

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9
Q

What bond causes branching? What enzyme forms this?

A

Alpha 1-6 glycosidic bond

Branching enzyme

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10
Q

What is glycogenolysis? Where does it occur and what is it stimulated by?

A
  • Glycogen breakdown
  • Occurs in liver + muscle
  • Occurs when glucose levels low
  • Stimulated by:
    • Glucagon
    • Adrenaline
    • Noradrenaline
    • GH
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11
Q

How does glycogen phosphorylase break the alpha 1-4 bonds?

A

Adds orthophosphate, releasing glucose 1-phosphate

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12
Q

What does debranching (transferase) enzyme do?

A

Moves the last 3 glucose residues to the non-reducing end of an existing chain

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13
Q

What does debranching (a(1,6) glycosidase) do?

A

Breaks alpha 1-6 bond, releasing the branched glucose

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14
Q

What does phosphorylase do?

A

Decreases chain length one by one, releasing molecules of G-1-P, which can the be converted into G6P by phosphoglucomutase, and then, in liver cells, Glucose 6 phosphatase converts G6P into glucose by removing phosphate and free glucose is released into the blood.

In skeletal muscle, G6P will enter the glycolysis pathway

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15
Q

Describe glycogen phosphorylase and what it’s regulated by

A
  • Large, multi-subunit enzyme, plays key role in glycogenolysis
  • Regulated by allosteric interactions that signal energy state of the cell - these can change the shape of the protein, henceforth regulating its activity.
  • Also regulated by reversible phosphorylation regulated by hormones such as insulin, glucagon, adrenaline and noradrenaline
  • Regulation of glycogen phosphorylase differs in muscle + liver 6
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16
Q

How is glycogen phosphorylase converted from its inactive b form into its active a form?

A

Converted by enzyme phosphorylase b kinase - It transfers a phosphate from an ATP molecule to one serine residue on each phosphorylase subunit

17
Q

How is glycogen phosphorylase activated in muscle? How is the activity of this enzyme controlled?

A

Activated by 5’-AMP, which forms when ATP is depleted. This removes the need for phosphorylation. 5’-AMP binds to the nucleotide-binding site.

ATP binds to the same site as the 5’-AMP, and blocks activation.

G-6-P also blocks 5’-AMP activation

In the liver, the activated phosphorylase a is inhibited by glucose, even after it has been activated after becoming phosphorylated.

18
Q

How is phosphorylase b kinase activated by Ca2+?

A

Calcium binding to the delta subunit causes a change in the quaternary structure of the enzyme, allowing binding of the delta subunit, and therefore increasing kinase activity in the absence of phosphorylation of the beta subunit

Max activity can only be achieve with Ca2+ AND phosphorylation

In liver, alpha-adrenergic activation stimulates Ca2+ release

19
Q

When is glycogen synthase activated and what stimulates it? What is it inactivated by?

A

Activates in time when blood glucose is high

Activated by ATP and G6P

Activated by dephosphorylation (by protein phosphatase-1)

Inactivated by phosphorylation (by protein kinase A)

Stimulated by insulin

20
Q

When is glycogen phosphorylase activated and what stimulates it? What is it inactivated by?

A
  • Activated when blood glucose is low
  • Activated by phosphorylation (by phosphorylase b kinase)
  • Inactivated by ATP and G6P
  • Inactivated by dephosphorylation (by protein phosphatase-1)
  • Stimulated by glucagon, adrenaline and noradrenaline
21
Q

How does insulin regulate glycogenolysis?

A

Inhibits breakdown of glycogen

22
Q

How does glucagon regulate regulate glycogenolysis?

A

Stimulates breakdown of glycogen in liver

23
Q

How does adrenaline regulate glycogenolysis?

A

Stimulates breakdown of glycogen in skeletal muscle

24
Q

Why is glucose-6-phosphate such an important intermediate?

A

G-6-P can be dephosphorylated back into glucose

G-6-P can be split into pyruvate

G-6-P can be converted into glycogen

G-6-P can be converted into Ribose-5-phosphate via the pentose phosphate pathway

25
Q

What is G6P converted into in the pentose phosphate pathway?

A

Ribose 5 phosphate, via decarboxylation and Reduction of 2NADP+ to produce 2NADP molecules

This Ribose 5 phosphate can then be converted into nucleotides and nucleic acid synthesis

26
Q

How does the pentose pathway allow for fatty acid synthesis?

A

The NADPH molecules that are produced can be oxidised, and in doing, the electron can bind to precursor and produce fatty acids, sterols etc.

The other NADPH molecule can be oxidised and convert GSSH into 2 GSH - These molecules prevent damage to cells due to oxidative stress

27
Q

What is gluconeogenesis?

A
  • Production of new glucose molecules (conversion of pyruvate into glucose)
  • Synthesised from triglycerides, lactate, amino acids
  • Takes place in:
    • 60% liver
    • 40% kidney
    • Small amount in intestine
  • Takes place when blood glucose levels are low, fastin or starving
28
Q

What are the 3 most important substrates for gluconeogenesis?

A

Alanine (Amino acid)

Lactate

Glycerol (From triglycerides)

29
Q

What do lactate and some amino acids produce?

A

Pyruvate

Amino acid that produce this include:

  • Alanine
  • Cysteine
  • Glycine
  • Serine
  • Theronine
  • Tryptophan
30
Q

What is pyruvate converted into in gluconeogenesis?

A

Oxaloacetic acid via pyruvate carboxylase

31
Q

What amino acids produce oxaloacetic acid?

A
  • Asparagine
  • Aspartate
  • Phenylalanine
  • Tyrosine
  • Isoleucine
  • Methionine
  • Threonine
  • Valine
  • Arginine
  • Glutamate
  • Proline histidine
32
Q

What does oxaloacetic acid produce in glucaneogenesis?

A

Phosphoenol pyruvate via Phosphoenol pyruvate carboxykinase

33
Q

What is phosphoenol pyruvate converted into in gluconeogenesis?

A

3C compound

34
Q

What is F1,6P converted into in gluconeogenesis?

A

F6P by Fructose 1,6 bisphosphatase

35
Q

What is G6P converted into in gluconeogenesis?

A

Glucose by glucose-6-phosphatase

36
Q

Describe gluconeogenesis in the liver

A

Pyruvate (produced from lactate, some amino acids) produces oxaloacetate via pyruvate carboxylase

Oxaloacetate produces Malate

Malate produces oxaloacetate

Oxaloacetate produces phosphoenol pyruvate via phosphoenol pyruvate carboxykinase