Glucose Metabolism in Physiological and Pathological Conditions Flashcards
How does glucose cross the cell membrane?
Facilitated diffusion via glucose transporters
Which tissues express GLUT1?
Foetal tissue
Cancer cells
Which tissues express GLUT2?
Liver
Kidney
Intesting
Pancreatic beta-cell
Which tissues express GLUT3?
Brain
Which tissues express GLUT4?
Muscle
Adipose tissue
What do glucose transporters depend on for the transport of glucose?
Availability of glucose in extracellular compartment
What is the relationship between insulin and GLUT4?
Insulin receptor stimulation facilitates translocation of GLUT4 to cell membrane
What are most of the GLUT4 molecules in cell associated with?
GLUT4 storage vesicles (GSVs) in cytosol
Is GLUT3 activity under the control of insulin?
No, it’s always active
What is the activity of GLUT3 at different plasma glucose concentrations?
High activity at all plasma glucose concentrations
What is the relationship between an enzyme’s Km value and its affinity for a substrate?
Low Km = high affinity
Why does GLUT3 have such a low Km?
Because needs to operate at full capacity regardless of plasma concentration because brain needs to work all the time
Why does GLUT4 have a moderate Km?
Needs to work well at higher plasma concentrations because body needs to store extra glucose at those times
Why does GLUT2 have such a high Km?
Glucose in hepatic portal vein can reach very high concentration after meal
Liver only takes up glucose for storage when its in plentiful supply
What is glucose intolerance in part attributed to?
Impaired glucose uptake by GLUT4
What are the blood glucose and GLUT4 levels in non-diabetics?
Maintain blood glucose levels
GLUT4 fluctuates
How do blood glucose levels change in people with diabetes?
Always high
Fluctuate a lot
Which tissues express enzymes for glycogenolysis?
Liver
Muscle
Kidney cortex
What is the role of glycogenolysis in muscle?
Sustain muscular activity
What is the role of glycogenolysis in the liver and kidney cortex?
Maintain blood glucose concentration
Which enzyme does muscle lack that disallows it from contributing to blood glucose maintenance via glycogenolysis?
Glucose-6-phosphatase
Which cells express enzymes for glycogenolysis in hypoxic conditions?
Astrocytes
Tumour cells
What is a neurovascular unit?
Blood capillary
Astrocyte
Neuron
What is the role of astrocytes in glucose metabolism?
Astrocytes take up glucose from capillary > store as glycogen
Why do astrocytes store glycogen?
Critical to protection of neurons in ischaemic stroke > still have source of glucose
What are the bonds in glycogen between glucose monomers?
Alpha-1,4-glycosidic linkage
Alpha-1,6-glycosidic linkage
Breaking which bond in glycogen gets the most amount of glucose?
Alpha-1,4-glycosidic linkage
What is a rate limiting step?
Catalyses irreversible reaction
Can be regulated
What is the enzyme involved in the rate-limiting step of glycogen breakdown?
Phosphorylase
What is UDP-glucose?
Activated glucose
What does UDP-glucose phosphorylase do?
Catalyses reversible reaction
Activates glucose
What is the rate-limiting enzyme in glycogen synthesis?
Glycogen synthase
What is the relationship between phosphorylase and glycogen synthase?
Inhibiting one activates the other
What are the fates of glucose-1-phosphate from glycogen?
Converted to glucose-6-phosphate
Used in
- Hypoxic tumour cells > pentose phosphate pathway
- Liver and kidney > glucose
- Muscle and tumour cells > energy
- Astrocytes > lactate > pyruvate in neurons
What are the liver and kidney specialised to do in terms of glucose metabolism?
Glucose producers
What are muscle and other organs specialised to do in terms of glucose metabolism?
Glucose utilisers
What is the function of glycolysis in muscles?
Generate ATP for muscle contraction
What is the function of glycolysis in the liver?
Generate acetyl-CoA for fatty acid synthesis
What is the function of liver and kidney cortex gluconeogenesis?
Generate glucose to maintain blood glucose levels
What is the difference between glucokinase and hexokinase?
Same enzyme
Called glucokinase in liver and kidney
Called hexokinase in other tissues
What are the rate limiting enzymes in glycolysis and glycogen breakdown?
1) (Glycogen) phosphorylase
2) Glucokinase/hexokinase
3) Phosphofructose kinase-1 (PFK-1)
4) Pyruvate kinase
What limits glycolysis?
Shortage of NAD
Where is the majority of NAD located?
In mitochondria > not available for glycolysis in cytosol
How is glycolysis sustained in anaerobic conditions?
NAD generated by lactate dehydrogenase-catalysed reaction
What does lactate dehydrogenase do?
Reduce pyruvate to lactate to make NAD
What happens to the lactate generated by lactate dehydrogenase?
Exported to liver
Liver converts to glucose
Glucose goes back to muscle for use
Does lactate dehydrogenase catalyse a reversible or irreversible reaction?
Reversible
What are the rate limiting enzymes of gluconeogenesis?
1) Glucose-6-phosphatase (G-6-Pase)
2) Fructo-1,6-bisphosphatase (FBPase-1)
3) Phosphoenolpyruvate carboxykinase (PEPCK)
What are the precursors of gluconeogenesis, and what are their main sources?
Muscle > alanine
Muscle > lactate
Adipose tissue > glycerol
What does adrenaline control in glucose metabolism in muscles, and why?
Stimulates glycogenolysis
To sustain muscular activity
What does insulin control in glucose metabolism in muscles, and why?
Stimulates glycogen synthesis
Store glycogen for future use
What does glucagon control in glucose metabolism in the liver and kidney cortex?
Stimulates glycogenolysis and gluconeogenesis
NOT glycolysis
To maintain blood glucose concentration
What does insulin control in glucose metabolism in the liver and kidney cortex?
Stimulates glycogen synthesis and glycolysis
To store glucose as glycogen and fatty acid
Where is adrenaline released from?
Adrenal medulla
Where is insulin released from?
Pancreas
Where is glucagon released from?
Pancreas
What is the role of glucocorticoids in glucose metabolism?
Long-term
Anti-insulin activity
What is the relationship between glucagon and insulin?
Reciprocally regulated
What stimulates the release of insulin?
High blood glucose
What stimulates the release of glucagon?
Low blood glucose
Which metabolic pathways are involved in gluconeogenesis?
Cori cycle
Alanine cycle
What is the Cori cycle?
Conversion of lactate from other tissues to glucose
What is the alanine cycle?
Conversion of alanine from muscle to glucose
Why can’t the citric acid cycle and electron transport chain supply enough ATP during rigorous muscular activity?
Limitation of O2 supply
How does muscle generate energy during rigorous muscular activity?
Derive all ATP from glycolysis
Rapid degradation of glycogen
Is glycolysis efficient?
No, only generates 2 ATP/glucose
How does the muscle provide alanine to the liver?
Protein breakdown
Pyruvate from glycolysis converted
How is alanine involved in the liver urea cycle?
Pyruvate + amino group > alanine (in muscle)
Carried to liver
Conversion to pyruvate liberates amino group > urogenesis > urea
When is most to all of the body’s glycogen stores used up?
Prolonged fasting
