L5. Glycogenolysis, Lipolysis and Gluconeogenesis Flashcards
LO
- Outline the fuel stores in the human body
- Describe the general principles of whole-body glucose homeostasis
- Predict the changes in blood glucose during the first few hours of a fast
- Recall how glycogen is mobilised from the liver and how the process is regulated
- Understand why muscle cannot contribute to blood glucose homeostasis
- Assess the dynamics of glycogen depletion in starvation
- Describe how fat is mobilised from the adipose tissue and how the process is regulated
- Understand the way in which glucagon and insulin signal tissue specific metabolic changes
- Predict the effect of fatty acid oxidation on glucose oxidation
- Describe the central features of the glucose fatty acid cycle and the Cori Cycle
- Summarise the patterns of fuel selection and mobilisation in early starvation
Starvation
Begins at the start of the post-absorptive period
- When all food has been digested
Reliant on blood and stored fuels
Some rules
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Glucose requirements
Parts of the kidney, skin and RBC have obligatory requirements for glucose
Strategies:
- Only use glucose unless you must (conserve it)
- Recycling, not fully oxidised, regenerate from lactate
- Anabolism from other things
Within the first few hours of starvation
- Tissues are using glucose (blood glucose falss and glucagon released by pancrease)
- To prevent hypoglycemia, liver releases glucose into the bloodstream (Therefore glucose stays Euglycemic ~4mM)
Glycogenolysis - Glucose metabolism
Occurs inside the liver cells
- Glycogen into glucose
Glucose-6-Phosphate is trapped inside the cytoplasm due to the phosphate attached
- G6P removes the phosphate with help of phosphorylase
- Glucose is released out the cell through GLUT-2.
Phosphorylase activation
Activated by glucagon
1. Glucagon binds to liver cell
2. Adenylyl cyclase creates cAMP, using an ATP
3. cAMP activates PKA
4. PKA phosphorylates kinase
5. Activated phosphorylase kinase, phosphorylates glycogen phosphorylase
6. Glycogen phosphorylase can break G-1-P off a glycogen chain
Each step is amplified, 1x glucagon can release 10,000 Glucose
- Uses a few ATP to invest in lots more ATP by ATP synthase and glycolysis steps
Branch points of Glycogen
Debranching enzyme cuts short glycogen branches that are 1-4 binded, and pastes the few glucoses on the longer chain
- Glucose binded at 1-6 bonds will undergo hydrolysis and will be released as glucose instead of G-1-P
Effects of low insulin and high glucagon
- Blood glucose below ~4mM, therefore Alpha cells in the pancrease stop releasing insulin and beta cells produce glucagon
- Stimulates glycogen breakdown in liver cells, and fat into FA in WAP.
WAP lipolysis
- Glucagon binds to a receptor on WAP cell surface
- cAMP released
- cAMP activates protein-kinase-A (PKA)
- PKA phosphorylates and activates Hormone-Sensitive lipase (HSL) and Perilipin
- Perilipin is around lipids and allows the HSL to access the fat within the lipid droplet
- HSL converts triacyl-glycerol into 3x FA and glycerol
- The FA and glycerol diffuse into the bloodstream, used as an alternative to glucose
- Liver can use glycerol to create glucose
Effect of FA Oxidation
FA will be oxidised to provide acetylCoA for krebs cycle
- BUT avoid oxidation for glucose
PDH
PDH is inactive when phosphorylated
- Opposite to glucagon to glucose system
High levels of ac-CoA turns it OFF
Insulin switches it ON
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Glucose-FA cycle
FA-Oxidation inhibits Glucose-Oxidation
In starvation we want PDH to be off
- PDH Kinase activity prevents PDH phosphatase activity
- PDH kinase is stimulated by acetyl-CoA
Prevents wasteful oxidation of pyruvate (only converts to lactate)
Beta-Oxidation turns off PDH by producing ac-CoA
- Stopping glucose oxidation
When PDH is off
Pyruvate cannot be oxidised to ac-CoA
- Only converted to Lacate by LDH
Lactate can be taken up by the liver and remade into glucose by gluconeogenesis
- Glucose conservation by recylcing (Cori-cycle)
- Can also happen from Glycerol
