Metabolism Session 1 Flashcards
Which tissues have an absolute requirement for glucose?
- Red blood cells (no mitochondria
- Neutrophils (respiratory burst)
- Cells of kidney medulla (low blood supply)
- Lens of eye (low blood supply)
What happens when glucose levels drop below 0.6 mmol/L?
- GLUT1 can no longer transport glucose into brain
= Brain damage and death occur
When can hypoglycaemia occur?
- Diabetes
- Acute alcohol poisoning
How is glycogen stored in muscles?*
- Granules
- 300g
- Between intra and intermyofibrils (in myofibrils/between myofibrils)
How is glycogen stored in the liver?*
- 100g
- Stored as granules in hepatocyte
What is the structure of glycogen?*
- Polymer of chains of glucose residues
- Organised like branches
- Originate from a dimer of glycogenin protein
- Tightly packed
- Not osmotically active
- Branches allow quick release of glucose
What is the difference between alpha-1-6 and alpha-1-4 glycosidic bonds?*
- Alpha-1-4 glycosidic bonds join the glucose residues to form chains
- Alpha-1-6 glycosidic bonds form branch points between 8-10 residues
What are the steps of glycogenesis?*
- Glucose + ATP = glucose-6-phosphate + ADP
(catalysed by hexokinase) - Glucose-6-phosphate = glucose-1-phosphate
(catalysed by phosphoglucomutase) - Glucose-1-phosphate + UTP + H2O = UDP-glucose + PPi
(catalysed by G1P uridylyltransferase) - Glycogen residues (n) + UDP-glucose = Glycogen (n+1) = UDP
What enzymes catalyse the last step of glycogenesis?
- Glycogen synthase (alpha-1-4, elongation)
- Branching enzyme (alpha-1-6, branching)
What is glycogenolysis?
Glycogen degeneraton
What are the steps of glycogenolysis?
Glycogen residues (n) + Pi = Glucose-1-phosphate + glycogen (n-1)
Glucose-1-phosphate = glucose-6-phosphate
(catalysed by phosphoglucomutase)
What enzymes are involved in the first step of glycogenolysis?
- Glycogen phosphorylase (1-4)
- Debranching enzyme (1-6)
What is the function of glycogen stores in the liver?*
- Glucose released into blood for use by other tissues
- Buffers plasma glucose levels
What is the function of glycogen stores in the muscle?*
- Lacks enzyme to buffer plasma glucose (GLUCOSE-6-PHOSPHATASE)
- Used by muscle for energy production
Describe glycogen metabolism.*
Slide 9.
What enzymes regulate glycogen synthesis and degradation?
- Glycogen synthase
- Glycogen phosphorylase
How do glucagon and adrenaline act on the 2 enzymes?
- Phosphorylate them
- Decrease activity of synthase
- Increase activity of phosphorylase
How does insulin act on the 2 enzymes?
- Dephosphorylation
- Increase activity of synthase
- Decrease activity of phosphorylase
How does AMP act on muscle?
It’s an allosteric activator of muscle glycogen phosphorylase (not of liver form)
Low energy states mobilise glycogen release.
What are glycogen storage diseases?
- Inborn metabolism errors
- Deficiency/dysfunction of enzymes of metabolism
- Can affect liver and/or muscle
What can excess glycogen stores cause?
Tissue damage
What can diminished glycogen stores cause?
- Hypoglycaemia
- Poor exercise tolerance
What is von Gierke’s disease?
Glucose-6-phosphatase deficiency that can cause hypoglycaemia.
What is McArdle disease?
Muscle glycogen phosphorylase deficiency.
What is gluconeogenesis?
Production of new glucose
When and where does gluconeogenesis occur?
- Beyond 8 hours of fasting as liver glycogen stores deplete
- Mostly liver, slightly in kidney
What are the 3 major precursors to gluconeogenesis?
LACTATE: from anaerobic glycolysis
GLYCEROL: from adipose tissue and triglyceride breakdown
AMINO ACIDS: alanine
What is the Cori cycle?*
- Glucose is metabolized to pyruvate and then to lactate in muscle
- Lactate is released into the blood and carried to the liver
- Reconverted to pyruvate and used for gluconeogenesis,
- Glucose is released into blood and travels back to muscle.
Why can’t acetyl-CoA or ethanol be converted into pyruvate?
There are 2 carbon atoms (CO2) lost per TCA cycle, and both compounds only have 2 carbons which would result in no net synthesis of glucose.
What are the three key enzymes in gluconeogenesis?*
- Glucose-6-phosphatase
- Fructose-1,6-bisphosphatase
- Phosphoenolpyruvate carboxykinase (PEPCK)
What reaction does glucose-6-phosphatase catalyse?
Glucose to glucose 6-phosphate
What reaction does fructose 1,6-bisphosphatase catalyse?
Fructose 6-phosphate to fructose 1,6-bisphosphate
What reaction does PEPCK catalyse?
Oxaloacetate to phosphoenolpyruvate.
Why are the three enzymes not simple reversals of corresponding glycolysis steps?
The three steps in glycolysis are IRREVERSIBLE and therefore need different enzymes.
Which 2 enzymes are regulated by starvation, prolonged exercise and stress?
- Fructose 1,6-bisphosphatase
- Phosphoenolpyruvate carboxykinase
What effects do glucagon and cortisol have on PEPCK and fructose 1,6-bisphosphatase?
- Increased amounts
- Stimulation of gluconeogenesis
What effects does insulin have on PEPCK and fructose 1,6-bisphosphatase?
- Decreased amounts
- Inhibition of gluconeogenesis as glucose is getting stored
What is the time course of glucose utilisation?
- Feeding: glucose from food used for 2 hours
- Glycogenolysis for up to 8-10 hours
- Gluconeogenesis happens from 10 hours onwards
How does lipid storage occur?*
Glycerol + 3 fatty acids = triacylglycerol + H2O
esterification to make, lipolysis to break
How are TAGs stored and why?
TAGs are hydrophobic.
- Stored in an anhydrous form
- In ADIPOSE TISSUE
How is storage and mobilisation of TAGs controlled?
Hormones
When are TAG stores used?
- Prolonged exercise
- Stress
- Starvation
- Pregnancy
What are adipocytes?*
- ‘White adipose tissue’
- Mainly TAGs and cholesterols esters in one large lipid droplet
- Cytoplasm and organelles pushed to edges
- Increase fourfold in size on weight gain before dividing.
How are dietary triacylglycerols mobilised?*
- Broken down in small intestine into fatty acids and glycerol by pancreatic lipase
- Reform in intestinal epithelial cells into TAGs and are packaged into chylomicrons
- Chylomicrons drain into lymph from thoracic duct to the left subclavian vein into blood
- Stored in adipose
- Controlled by hormone sensitive lipase
- Mobilised as a FA-albumin complex
- Into tissues for energy
How does hormone sensitive lipase work?
- Releases TAGs with high glucagon and adrenaline
- Inhibits TAG release with insulin
Why can’t the brain use fatty acids for energy?
They do not cross the blood brain barrier easily.
Where does lipogenesis occur?
Liver
Describe the process of fatty acid synthesis **
DIAGRAM PAGE 20 PLEASE!!
- Glycolysis in cytoplasm
- Pyruvate combines with Acetyl CoA + OAA = citrate (mitochondria)
- Citrate cleaved back into Acetyl-CoA + OAA in cytoplasm
- Acetyl-CoA carboxylase produces malonyl-CoA from Acetyl-CoA
- Fatty acid synthase complex builds fatty acids by sequential addition of 2 carbon units provided by malonyl-CoA
What does lipogenesis require?
- ATP
- NADPH
What activates Acetyl-CoA carboxylase?
Insulin and citrate
What inhibits Acetyl-CoA carboxylase?
Glucagon, adrenaline and AMP
What are the features of fatty acid oxidation?
- Remove C2
- Removed as Acetyl-CoA
- Mitochondria
- Oxidative (NADH + FAD2H made)
- Inhibited by insulin
- Stimulated by glucagon and adrenaline
What are the features of fatty acid synthesis?
- Adding C2
- Added as malonyl-CoA
- Cytoplasm
- Reductive (uses ATP and NADPH)
- Inhibited by glucagon/adrenaline
- Stimulated by insulin
How does fat mobilisation occur?*
- Hormone sensitive lipase is activated and phosphorylated by glucagon and adrenaline
- Released into the blood where it splits into glycerol and FA
Where does glycerol travel?
To the liver to be used as a carbon source for gluconeogenesis
Where do fatty acids travel?
FA-Albumin complex in blood to muscles and other tissues, where beta oxidation will occur.
How much fat is in an average 70kg man?
15kg of triacylglycerol which is 600,000kJ
