Post-absorption Processing of Carbohydrate Flashcards
What is the difference between the fed state and the fasting state?
- 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’.
What happens in the fasting state?
- 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’.
What is the function of ketone bodies?
- Ketone bodies are transported from the liver to other tissues, where they can be reconverted to acetyl-CoA = TCA cycle.
List simple and complex carbohydrates.
Simple: mono and di-saccharides
- Glucose & fructose, lactose & sucrose.
Complex:
- Starch, glycogen, cellulose.
What are the enzymes that are involved in carb digestion?
- Saliva: α-Amylase breaks down starch & glycogen, pH restricted.
- Pancreas: Pancreatic α-Amylase
- Gut mucosa Oligo- & Di-saccharidases:
*Isomaltase & Sucrase, Maltase & Lactase.
Where does absorption happen?
- Mostly in the duodenum & upper jejunum.
What is Gluconeogenesis?
- The synthesis of glucose from lactate, pyruvate, glycerol, etc.
- Stimulated by Glucagon.
What are Substrates for gluconeogenesis?
- Lactate via the ‘Cori Cycle’.
- Glycerol from fat stores (triglycerides).
- Amino-acids from tissue protein breakdown.
What are the important steps in Gluconeogenesis?
- Pyruvate carboxylase (biotin is a co-factor):
- Pyruvate to oxaloacetate. - PEP carboxykinase:
- Oxaloacetate to PEP - Fructose 1,6 bisphosphatase
- Glucose-6-phosphatase (Also requires glucose-6-phosphate translocase).
What are the products of Gluconeogenesis?
- A maximum of 2 GTP, 4ATP and 2 NADH consumed.
- Energy needed is dependent on the substrate.
What is glycogen and what are its stores in the body?
- A polymer made of glucose.
- Liver (used to maintain blood glucose) and muscle (fuel reserve for ATP synthesis during muscle contraction).
What happens when glycogen stores are depleted?
- When glycogen depleted, some tissues synthesise glucose via gluconeogenesis using amino acids.
What is the structure of glycogen?
- A branched polymer of -D-glucose units joined by a-1,4 glycosidic bonds.
- Connected chains joined by -1,6 glycosidic bonds (‘branch points’).
Discuss glycogen synthesis.
- 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.
What provides ‘building blocks’ for glycogen?
- UDP-glucose.
What happens if theres no glycogen left in synthesis?
- 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.
Describe Glycogenolysis (glycogen breakdown).
- 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’.
What is limit dextrin?
- A structure produced when Glycogen phosphorylase stops 4 glucose residues before each branch point.
What happens to the Glucose-1-p that’s produced?
- 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.
What are the 2 key enzymes in glycogen metabolism?
- Glycogen Synthase.
- Glycogen phosphorylase.
- Respond to levels of metabolites and energy
requirements of the cell.
What are the 2 levels of regulation?
- Allosteric regulation.
- Hormonal regulation.
What is allosteric regulation of glycogen?
- Glucose-6-P allosterically:
- Activates Glycogen Synthase.
- Inhibits Glycogen Phosphorylase. - In muscle:
- Ca2+ (released during contraction) acts indirectly to activate Glycogen Phosphorylase.
- High AMP as result of anoxia and ATP depletion activates Glycogen Phosphorylase.
How do hormones act to control the activity of these enzymes?
- Reversible phosphorylation / dephosphorylation is used widely in cells to control enzyme activity.
- E.g. glucagon and insulin
- Provides a useful ‘signalling’ system also:
How does phosphorylation change enzyme activity?
How do Glucagon & Adrenalin promote phosphorylation?
- They activate cAMP-dependent Protein Kinase A.
- Net effect = glycogen breakdown.
- Glycogen synthase activity decreased and glycogen phosphorylase activity increased.
How does insulin promote phosphorylation?
- It activates another protein kinase that causes
dephosphorylation. - Net effect: glycogen synthesis.
- Glycogen synthase activity increased and glycogen phosphorylase activity decreased.
Discuss the co-ordinated regulation of fat & carbohydrate metabolism by hormones.
What controls Hormone-sensitive Adipose Tissue Lipase?
- Phosphorylation / dephosphorylation! (active when phosphorylated by PKA - lipolysis)
What are storage disorders?
- Genetic diseases characterised by abnormal
accumulation of lipids or carbohydrates.
What are the Glycogen Storage Disorders (GSDs)?
- 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
How do GSDs affect the liver and muscle?
- Disease presentation & severity depend on the
role played by the enzyme & its tissue-specificity.
What are the signs of GSDs?
- Hypoglycaemia.
- Muscle pain / cramps / weakness.
List some GSDs.
- GSD V – McArdle Disease.
- Muscle glycogen phosphorylase deficiency.
- Muscle fatigue, myoglobinuria. - 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).
