Carbohydrate Metabolism Flashcards
What is the critical blood glucose value?
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
Why is glucose stored as glycogen?
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
What is glycogenesis?
- Glycogen synthesis
- Takes place in liver and skeletal muscle
- Occurs when blood glucose levels high
What regulates glycogenesis?
Insulin
What is G-6-P converted into in glycogenesis? What enzyme regulates this?
Glucose 1 phosphate by phosphoglucomutase
What is G-1-P converted into? What enzyme regulates this?
UDP- glucose by UDP-glucose-pyrophosphorylase
Glucose is activated by the reaction with UTP
UTP (uridine triphosphate) is converted into PPI
What does UDP-glucose react with?
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.
What is the bond between each glucose molecule attached to glycogenin?
Alpha 1-4 glycosidic bond (straight chain)
Alpha 1-6 glycosidic bond (branched chain, this bond causes the branching)
What bond causes branching? What enzyme forms this?
Alpha 1-6 glycosidic bond
Branching enzyme
What is glycogenolysis? Where does it occur and what is it stimulated by?
- Glycogen breakdown
- Occurs in liver + muscle
- Occurs when glucose levels low
- Stimulated by:
- Glucagon
- Adrenaline
- Noradrenaline
- GH
How does glycogen phosphorylase break the alpha 1-4 bonds?
Adds orthophosphate, releasing glucose 1-phosphate
What does debranching (transferase) enzyme do?
Moves the last 3 glucose residues to the non-reducing end of an existing chain
It facilitates the transfer of glucose residues from the branched ends of glycogen to the main linear chain, effectively debranching the molecule
What does debranching (a(1,6) glycosidase) do?
Breaks alpha 1-6 bond, releasing the branched glucose
What does phosphorylase do?
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. Phosphorylase is activated by phosphorylation but regulated by other factors
In skeletal muscle, G6P will enter the glycolysis pathway
Describe glycogen phosphorylase and what it’s regulated by
- 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
How is glycogen phosphorylase converted from its inactive b form into its active a form?
Converted by enzyme phosphorylase b kinase - It transfers a phosphate from an ATP molecule to one serine residue on each phosphorylase subunit
How is glycogen phosphorylase activated in muscle? How is the activity of this enzyme controlled?
Activated by 5’-AMP, which forms when ATP is depleted. This removes the need for phosphorylation. 5’-AMP binds to the nucleotide-binding site, one of the allosteric binding sites on the enzyme
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.
How is phosphorylase b kinase activated by Ca2+?
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
When is glycogen synthase activated and what stimulates it? What is it inactivated by?
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
When is glycogen phosphorylase activated and what stimulates it? What is it inactivated by?
- 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
How does insulin regulate glycogenolysis?
Inhibits breakdown of glycogen
How does glucagon regulate regulate glycogenolysis?
Stimulates breakdown of glycogen in liver
How does adrenaline regulate glycogenolysis?
Stimulates breakdown of glycogen in skeletal muscle
Why is glucose-6-phosphate such an important intermediate?
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
What is G6P converted into in the pentose phosphate pathway?
Ribose 5 phosphate, via decarboxylation and Reduction of 2NADP+ to produce 2NADPH molecules
This Ribose 5 phosphate can then be converted into nucleotides and nucleic acid synthesis
How does the pentose pathway allow for fatty acid synthesis?
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
What is gluconeogenesis?
- 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
What are the 3 most important substrates for gluconeogenesis?
Alanine (Amino acid)
Lactate
Glycerol (From triglycerides)
What do lactate and some amino acids produce?
Pyruvate
Amino acid that produce this include:
- Alanine
- Cysteine
- Glycine
- Serine
- Theronine
- Tryptophan
What is pyruvate converted into in gluconeogenesis?
Oxaloacetic acid via pyruvate carboxylase
What amino acids produce oxaloacetic acid?
- Asparagine
- Aspartate
- Phenylalanine
- Tyrosine
- Isoleucine
- Methionine
- Threonine
- Valine
- Arginine
- Glutamate
- Proline histidine
What does oxaloacetic acid produce in glucaneogenesis?
Phosphoenol pyruvate via Phosphoenol pyruvate carboxykinase
What is phosphoenol pyruvate converted into in gluconeogenesis?
3C compound
What is F1,6P converted into in gluconeogenesis?
F6P by Fructose 1,6 bisphosphatase
What is G6P converted into in gluconeogenesis?
Glucose by glucose-6-phosphatase
Describe gluconeogenesis in the liver
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
