Post-absorption Processing of Carbohydrate

Question 1

What is the difference between the fed state and the fasting state?

Answer 1

• Fed:
  1. Nutrients plentiful = Build up stores.
  2. ↑ Plasma glucose.
  3. ↑ Plasma amino-acids
  4. ↑ Plasma triglycerides (chylomicrons)
• Control via: ↑ insulin secretion by the pancreas
  ↓ secretion of glucagon.
• Response: [Anabolic].
  1. Liver – makes glycogen, proteins & triglycerides (VLDL).
  2. Adipose – makes triglycerides.
  3. Muscle – makes protein.
• Tissues use glucose as a ‘fuel’.

Question 2

What happens in the fasting state?

Answer 2

• Fasting:
  1. Nutrients scarce = Use stores / maintain function.
  2. ↓ plasma glucose
  3. ↓ plasma amino-acids
  4. ↓ plasma triglycerides
• Control:
  1. ↓ insulin secretion and ↑ secretion of glucagon & adrenaline.
• Response: catabolic
  1. Liver – glycogenolysis, gluconeogenesis, -oxidation & ketogenesis.
  2. Adipose – lipolysis.
  3. Muscle – uses fatty-acids & ketone bodies as ‘fuel’ & proteolysis supplies AAs to liver.
• Brain – uses glucose & ketone bodies as ‘fuel’.

Question 3

What is the function of ketone bodies?

Answer 3

• Ketone bodies are transported from the liver to other tissues, where they can be reconverted to acetyl-CoA = TCA cycle.

Question 4

List simple and complex carbohydrates.

Answer 4

Simple: mono and di-saccharides
- Glucose & fructose, lactose & sucrose.
Complex:
- Starch, glycogen, cellulose.

Question 5

What are the enzymes that are involved in carb digestion?

Answer 5

• Saliva: α-Amylase breaks down starch & glycogen, pH restricted.
• Pancreas: Pancreatic α-Amylase
• Gut mucosa Oligo- & Di-saccharidases:
  *Isomaltase & Sucrase, Maltase & Lactase.

Question 6

Where does absorption happen?

Answer 6

• Mostly in the duodenum & upper jejunum.

Question 7

What is Gluconeogenesis?

Answer 7

• The synthesis of glucose from lactate, pyruvate, glycerol, etc.
• Stimulated by Glucagon.

Question 8

What are Substrates for gluconeogenesis?

Answer 8

• Lactate via the ‘Cori Cycle’.
• Glycerol from fat stores (triglycerides).
• Amino-acids from tissue protein breakdown.

Question 9

What are the important steps in Gluconeogenesis?

Answer 9

1. Pyruvate carboxylase (biotin is a co-factor):
   - Pyruvate to oxaloacetate.
2. PEP carboxykinase:
   - Oxaloacetate to PEP
3. Fructose 1,6 bisphosphatase
   - Glucose-6-phosphatase (Also requires glucose-6-phosphate translocase).

Question 10

What are the products of Gluconeogenesis?

Answer 10

• A maximum of 2 GTP, 4ATP and 2 NADH consumed.
• Energy needed is dependent on the substrate.

Question 11

What is glycogen and what are its stores in the body?

Answer 11

• A polymer made of glucose.
• Liver (used to maintain blood glucose) and muscle (fuel reserve for ATP synthesis during muscle contraction).

Question 12

What happens when glycogen stores are depleted?

Answer 12

• When glycogen depleted, some tissues synthesise glucose via gluconeogenesis using amino acids.

Question 13

What is the structure of glycogen?

Answer 13

• A branched polymer of -D-glucose units joined by a-1,4 glycosidic bonds.
• Connected chains joined by -1,6 glycosidic bonds (‘branch points’).

Question 14

Discuss glycogen synthesis.

Answer 14

• UDP-glucose provides the ‘building blocks’
  for glycogen.
• Glycogen synthase adds successive glucose units to the non-reducing ends of growing chains, forming the a-1,4 bonds.
  **It can only make existing glycogen chains longer.

Question 15

What provides ‘building blocks’ for glycogen?

Answer 15

• UDP-glucose.

Question 16

What happens if theres no glycogen left in synthesis?

Answer 16

• The protein Glycogenin acts as a primer accepting glucose units to form a new chain.
• Branches are made by the ‘Branching enzyme’:
  Amylo-(1-4)  (1-6) transglucosidase.

Question 17

Describe Glycogenolysis (glycogen breakdown).

Answer 17

• Glycogen phosphorylase cleaves a-1,4 glycosidic bonds.
• It cleaves successive glucose units off the chains, starting at the non-reducing ends, releasing them as glucose-1-phosphate.
• Branches are removed by the ‘Debranching enzyme’.

Question 18

What is limit dextrin?

Answer 18

• A structure produced when Glycogen phosphorylase stops 4 glucose residues before each branch point.

Question 19

What happens to the Glucose-1-p that’s produced?

Answer 19

• Its converted to glucose-6-P by the action of
  Phosphoglucomutase.
• In the liver, Glucose-6-phosphatase and Glucose 6 P translocase then converts glucose-6-P to glucose for release into the Bloodstream.
• In the muscle: Glucose-6-P goes into glycolysis directly to produce energy.

Question 20

What are the 2 key enzymes in glycogen metabolism?

Answer 20

1. Glycogen Synthase.
2. Glycogen phosphorylase.
   - Respond to levels of metabolites and energy
   requirements of the cell.

Question 21

What are the 2 levels of regulation?

Answer 21

• Allosteric regulation.
• Hormonal regulation.

Question 22

What is allosteric regulation of glycogen?

Answer 22

1. Glucose-6-P allosterically:
   - Activates Glycogen Synthase.
   - Inhibits Glycogen Phosphorylase.
2. In muscle:
   - Ca2+ (released during contraction) acts indirectly to activate Glycogen Phosphorylase.
   - High AMP as result of anoxia and ATP depletion activates Glycogen Phosphorylase.

Question 23

How do hormones act to control the activity of these enzymes?

Answer 23

• Reversible phosphorylation / dephosphorylation is used widely in cells to control enzyme activity.
• E.g. glucagon and insulin
• Provides a useful ‘signalling’ system also:

Question 24

How does phosphorylation change enzyme activity?

Answer 24

Question 25

How do Glucagon & Adrenalin promote phosphorylation?

Answer 25

• They activate cAMP-dependent Protein Kinase A.
• Net effect = glycogen breakdown.
• Glycogen synthase activity decreased and glycogen phosphorylase activity increased.

Question 26

How does insulin promote phosphorylation?

Answer 26

• It activates another protein kinase that causes
  dephosphorylation.
• Net effect: glycogen synthesis.
• Glycogen synthase activity increased and glycogen phosphorylase activity decreased.

Question 27

Discuss the co-ordinated regulation of fat & carbohydrate metabolism by hormones.

Answer 27

Question 28

What controls Hormone-sensitive Adipose Tissue Lipase?

Answer 28

• Phosphorylation / dephosphorylation! (active when phosphorylated by PKA - lipolysis)

Question 29

What are storage disorders?

Answer 29

• Genetic diseases characterised by abnormal
  accumulation of lipids or carbohydrates.

Question 30

What are the Glycogen Storage Disorders (GSDs)?

Answer 30

• Abnormal synthesis or degradation of glycogen.
• Due to a defect in the genes coding for enzymes
  involved in glycogen metabolism.
• At least 12 different GSDs

Question 31

How do GSDs affect the liver and muscle?

Answer 31

• Disease presentation & severity depend on the
  role played by the enzyme & its tissue-specificity.

Question 32

What are the signs of GSDs?

Answer 32

• Hypoglycaemia.
• Muscle pain / cramps / weakness.

Question 33

List some GSDs.

Answer 33

1. GSD V – McArdle Disease.
   - Muscle glycogen phosphorylase deficiency.
   - Muscle fatigue, myoglobinuria.
2. GSD I – Von Gierke’s Disease. Most common.
   - Glucose-6-phosphatase deficiency.
   - Hypoglycaemia, lactic acidosis (accumulation of glycolysis intermediates, phosphorylated glucose cannot leave the cell and is converted to lactate), ketosis, hepatomegaly (accumulation of glycogen and fat).