carbohydrate metabolism

Question 1

what are the symptoms of hypo and hyperglycaemia?

Answer 1

HYPOGLYCAEMIA (too little glucose): 
→ muscle weakness 
→ loss of coordination 
→mental confusion 
→ sweating
→ hypoglycaemic coma and death 

HYPERGLYCAEMIA
(too much glucose):
→ non-enzymatic modifications of proteins (cataracts, lipoproteins important in atherosclerosis, etc.)
→hyperosmolar coma

Question 2

what happens when there is excess glucose in the body?

Answer 2

→glycogen synthesis
→ pentose phosphate pathway
→ fatty acid synthesis

Question 3

what happens when there is a lack of glucose in the body?

Answer 3

→glycogen breakdown

→ gluconeogenesis

Question 4

what happens to glucose in the liver?

Answer 4

→ Glucose from the bloodstream gets transported into the liver.

→ using glucokinase, (ATP → ADP) gets phosphorylated to Glucose-6-Phosphate.

→ It could get converted to Glycogen (and be converted back). This helps maintain glucose levels.

→ It could be converted to Ribose-5-Phosphate (in the Pentose Phosphate Pathway)

→ It could be converted to Pyruvate (and back). This is for aerobic/anaerobic respiration.

Question 5

what are the steps in glycogen synthesis?

Answer 5

1→ Glucose-6-Phosphate is converted to Glucose-1-Phosphate by Phosphoglucomutase.

→ Glucose-1-Phosphate is then converted to UDP-Glucose via UDP-glucose-pyrophosphorylase (using UTP).

→ The UDP-Glucose then combined with Glycogenin to initiate glycogen synthesis, as it acts as a primer required by Glycogen Synthase (GS) to attach additional glucose molecules.

→ Glycogen Synthase facilitates the addition of additional glucose monomers via 1-4 glycosidic bonds)

Question 6

how are branches in glycogen formed?

Answer 6

→ every 11 glucose monomers that are added, some are transferred (by branching enzymes) to be in a branch via a 1-6 glycosidic bond.

Question 7

why is glycogen used?

Answer 7

→glycogen cannot be stored (as it is osmotically active) - →400 mM glucose is stored as 0.01 μm glycogen (so 10 mM)
→ fat can’t be mobilized as readily
→fat can’t be used as an energy source in the absence of oxygen
→fat can’t be converted in to glucose

Question 8

what are the four enzymes needed to break down glycogen and what do they do?

Answer 8

→phosphorylase breaks the α 1-4 links
→translocase transports G-6-P to ER for further modification
→ debranching enzyme - debranches (acts on 1-6 links) →phosphoglucomutase - converts G1P to G6P

Question 9

what are the five enzymes needed to form glucose?

Answer 9

→phosphorylase
→translocase
→debranching enzyme
→phosphoglucomutase
→glucose 6 phosphatase converts G6P to glucose (present in the liver and kidney, but not muscle)

Question 10

how is glycogen broken down?

Answer 10

→The way glycogen is broken down is the reverse of synthesis.

→The enzyme important for breaking down glycogen will remove individual units until it eventually removes the whole branch.

→The α 1-4 links are broken to remove the units individually, done by the enzyme Phosphorylase.

→This gives G1P, which are then converted to G6P by Phosphoglucomutase.

Question 11

how does glycogen phosphorylase work?

Answer 11

→key enzyme in glycogenolysis and its activity forms G1P.

→large, multisubunit enzyme.

→Many Phosphorylase molecules are bound to each glycogen particle.

→The G6P ultimately formed provides fuel for working muscles.

→In the liver, the G6P is dephosphorylated (by G-6-Phosphatase) and secreted into the blood, maintaining the 5mM blood sugar concentration.

Question 12

how is glycogen phosphorylase controlled?

Answer 12

→ interchangeable active and inactive forms.

→The inactive form is Phosphorylase B, and the active form is Phosphorylase A.

→Phosphorylase is an example of an “allosteric” enzyme; it is activated by phosphorylation, but modulated by other factors.

Question 13

how is glycogen breakdown inhibited in the liver?

Answer 13

→ In the liver, glycogen breakdown by Phosphorylase is inhibited by the presence of glucose, even after the enzyme has been activated to the a form by being phosphorylated.

Question 14

how is phosphorylase b activated in muscle?

Answer 14

→In muscle, Glycogen Phosphorylase b can also be activated without being phosphorylated.

→5´-AMP (which forms when ATP is depleted) binds to another allosteric site, the nucleotide-binding site.

→ATP will bind to the same site, blocking the activation.

→Glucose-6-phosphate also blocks 5´-AMP activation.

Question 15

what hormones control the regulation of glycogenolysis in the liver and in the muscle?

Answer 15

→Different hormones stimulate it in different places.

→in the liver, it is stimulated by Glucagon

→ in the muscle, it is stimulated by Adrenaline (Cortisol is a weak stimulus of glycogenolysis, and Insulin inhibits it.)

Question 16

describe the hormonal regulation of glycogenolysis

Answer 16

→1) Adenylate Cyclase is stimulated to make more Cyclic AMP.

→2) This activates Protein Kinase A.

→3)activates Phosphorylase Kinase

→4) activates Phosphorylase, turning it from Phosphorylase B to Phosphorylase A.

→5) removes glucose molecules from Glycogen as G1P.

(Activated Protein Kinase inhibits the activity of Glycogen Synthase, converting the active Glycogen Synthase A to the inactive form Gluycogen Synthase B)

Question 17

How is Phosphorylase Kinase regulated?

Answer 17

→Phosphorylase Kinase is under dual regulation via two different receptor types.

→The most important is through the elevation of cAMP and the activation of PKA.

→The other is calcium-mediated through the alpha adrenergic/IP3 pathway.

Question 18

how is glycogen synthesis and degradation reciprocally regulated?

Answer 18

→via Glycogen Synthase and Glycogen Phosphorylase.

→Glycogen Synthase is activated in times of plenty glucose.

→Glycogen Phosphorylase is activated when glucose is in short supply.

Question 19

what are Glycogen Synthase and Glycogen Phosphorylase activated and inhibited by?

Answer 19

GLYCOGEN SYNTHASE:
→activated by ATP and G6P
→inactivated by phosphorylation (by Protein Kinase A)
→ activated by dephosphorylation (by Protein Phosphatase-1)

GLYCOGEN PHOSPHORYLASE:
→ inactivated by ATP and G6P
→activated by phosphorylation (by Phosphorylase B Kinase)
→inactivated by dephosphorylation (by Protein Phosphatase-1)

Question 20

what is the significance of the pentose phosphate pathway?

Answer 20

→The pentose phosphate pathway is a metabolic pathway parallel to glycolysis.

→The two most important products from this process are the ribose-5-phosphate sugar used to make DNA and RNA, and the NADPH molecules which help with building other molecules.

→This pathway is special because no energy in the form of ATP is produced or used up in this pathway.

Question 21

what is the significance of gluconeogenesis?

Answer 21

→The body maintains the blood glucose because it’s the preferred fuel for the brain.

→We use up more than our total body reserves can hold, so we constantly need to be making more.

Question 22

what are the steps in gluconeogenesis?

Answer 22

1) Pyruvate (3C) is converted to Oxaloacetic Acid by Pyruvate Carboxylase.
2) Oxaloacetic Acid is then converted to Phosphoenol Pyruvate by Phosphoenol Pyruvate Carboxykinase.
3) Phosphoenol Pyruvate is then converted to the C3 molecule (GAP)
4) GAP is then converted to Fructose-1,6-bisphosphate
5) Fructose-1,6-bisphosphate is then converted to Glucose-6-Phosphate by Fructose Bisphosphatase.
6) Glucose-6-Phosphate is then converted to Glucose by Glucose-6-Phosphatase.

→Some amino acids can also be converted back to glucose. These are called the Gluconeogenic amino acids.
→They can be fed in at different parts of the process.
→(Note: Glucagon inhibits Phosphofructokinase and Pyruvate Kinase, ensuring that the two pathways don’t happen simultaneously)

Question 23

how does pyruvate get converted to oxaloacetate in the liver?

Answer 23

1) Pyruvate is brought into the mitochondria (in the liver) via a Pyruvate carrier.
2) Pyruvate is converted to Oxaloacetate by Pyruvate Carboxylase.
3) To leave the liver, the Oxaloacetate is converted to Malate.
4) The Malate is then brought out of the mitochondria.
5) Now outside, it is converted back to Oxaloacetate and then the process continues.

Question 24

what are the most important substrates in gluconeogenesis?

Answer 24

→The most important substrates for Gluconeogenesis are the amino acid Alanine, Lactate and Glycerol.

Question 25

what does gluconeogenesis do and where does this take place?

Answer 25

→Gluconeogenesis converts pyruvate to glucose.

→It takes place mostly in the liver, and a little in the kidney (during starvation, kidney gluconeogenesis rises up to 40%).

Question 26

what is the fate of G6P in muscle and in liver?

Answer 26

→The fate of this G6P will vary depending on the tissue.

→ In muscle, it can be used for ATP Synthesis for its own use.

→The muscle, however, cannot use it to control blood glucose as it doesn’t have the enzyme to convert G6P to glucose.

→ In the liver, it does contain the enzyme needed to convert G6P to glucose (Glucose-6-Phosphatase), and so can control blood glucose levels.

Question 27

how is G6P made during glycogen breakdown?

Answer 27

→The residues are removed till you get to a certain length (an end portion of a particular branch).

→This portion left is then broken off and moved onto the end of the main chain.

→This is done by the first kind of debranching enzyme, Translocase.

→Glucosidase is the second kind of debranching enzyme which removes the final residue left on the branch, releasing it as G6P (that could be converted to glucose in the liver)