8. the starved state Flashcards
when does the fasting state start?
what type of state is the body in during this time?
when does the starved state start?
2-4 hours after a meal
catabolic
3 days- metabolically different to fasted state
during starvation, what two factors determine how long you can survive for?
amount of adipose tissue and protein levels
what can protein depletion lead to?
organ malfunctioning and infections
two priorities of the body during starvation
-Maintain adequate blood glucose
Mobilise fatty acids & synthesise/release ketone bodies for other tissues
why isn’t it practical to store all energy as glycogen?
binds water as polar molecule
organ fuel use: brain
- Glucose is primary fuel (except during starvation)
- Ketones used in starvation
- FAs can’t cross BBB as bound to albumin
Organ fuel use:muscle
- Glucose, FA, & Ketone Bodies
- Glycogen store can be converted to glucose by glucose-6-phosphate for contraction
- FAs are used by resting muscle (85%) of needs
- Glucose prioritized for contraction
organ fuel use: heart
- FAs, ketone bodies, lactate
- No glycogen reserves. So prefers fatty acids and ketones
organ fuel use: adipose tissue
what is needed to create triacylglycerols?
what else is needed?
- Needs glycerol 3-phosphate to create triacylglcyerols
- ∴ need glucose for glycolytic intermediate Dihydroxyacetone phosphate (reduction = G-3-P)
organ fuel use: liver
- Provides fuel to brain, muscle & peripheral organs
- Metabolises carbohydrates (~ 2/3rds of glucose) to form glycogen
- Turns fatty acids into ketone bodies
Utlises α-ketoacids derived from amino acids
carbohydrate metabolism in liver:
what is the main role? what else is produced?
which metabolic pathway is used first?
what does in increase glucagon: insulin lead to?
where are the skeletons from gluconeogenesis derived from?
- the main role is to produce glucose by glycogenolysis & gluconeogenesis. Also , ketone bodies are produced for non-glucose dependent tissues.
- Glycogen degradation occurs first, followed by gluconeogenesis
-Increased glucagon-to-insulin ratio = PKA-mediated phosphorylation of glycogen phosphorylase kinase
Increased phosphorylation of glycogen phosphorylase
•The skeletons from gluconeogenesis are derived from glucogenic amino acids, lactate from muscle and glycerol from adipose tissue
- Gluconeogenesis is favored by fructose 1,6-bisphosphatase activation & PEPCK induction
•Some amino acids are used for biosynthetic functions
- e.g. heme synthesis, neurotransmitters formation
•Nitrogen is converted to urea (output decreases as starvation continues)
fat metabolism in liver
•Fatty acid oxidation is the major energy source in liver tissue
- Malonyl CoA drop permits CPT-1 to activate & β-oxidation occurs
- NADH produced inhibits the TCA cycle
- Acetyl CoA produced activates Pyruvate carboxylase &inhibits pyruvate dehydrogenase
- Gluconeogenesis is increased
•Increased Ketone body synthesis occurs (acetoacetate & 3-hydroxybutyrate)
- Not used by liver as lacking thioporase
- Favoured when acetyl CoA exceeds TCA cycle capacity
adipose tissue: carbohydrate metabolism
Glucose transport is depressed as GLUT-4 is insulin sensitive
- Reduced glycolysis etc.
- Reduced TAG synthesis
adipose: fat metabolism
- Adipose triacylglycerols are mobilized by lipolysis
- releases FAs & glycerol
- PKA-mediated phosphorylation and activation of HSL
- enhanced by elevated catecholamines
- FA usage increases with length of fast
•Increased Release of Fatty acids
- Hydrolysis of TAGs releases FAs
- Bound to albumin they act as fuel for a variety of tissues
- Glycerol can also be used as a gluconeogenic precursor in the liver
•Decreased uptake of Fatty acids
- Adipose LPL activity is low
resting skeletal muscle
•During fasting, resting muscle moves further from glucose to FAs & ketone bodies
- For contraction: as glycogen depleted, FAs mobilized from TAG (Adipose tissue) become the dominant energy source.
resting skeletal muscle: carbohydrate metabolism
lipid metabolism
protein metabolism
- Glucose transport is depressed as GLUT-4 is insulin sensitive
- Reduced glycolysis etc.
•Lipid Metabolism
- During the first 2 weeks, muscle use FA from adipose tissue & ketone bodies from liver
- After 3 weeks, muscle reduces use of ketone bodies (save for the brain)
•Protein Metabolism
- During the early fast: rapid breakdown of muscle protein (↑ liver gluconeogenesis)
- alanine & glutamine are the most important
- initiated by fall in insulin (no glucagon receptors)
brain and kidney
•In prolonged fasting (beyond 2-3 weeks) plasma ketone levels rise significantly, and replace glucose
-Some glucose needed for neurotransmitters
•As glucose isn’t required, protein catabolism for gluconeogenesis isn’t required
- Protein degradation can be reduced
As starvation continues, the kidney’s role gets more important.
•Expresses the enzymes of gluconeogenesis
- In late fasting 50% of gluconeogenesis occurs here
- Uses self generated glucose
- Compensates for acidosis by ketone bodies- glutamine taken up from blood stream released from muscle, acted on by renal glutaminase and gulamate dehydrogenase- make alpha ketoglutarate and ammonia which absorbs protons and excreeds via urine
diabetes mellitus
•A heterogenous metabolic disease group
- Multifactorial, polygenic diseases
- Characterised by hyperglycemia
- Relative small or absolute deficiency in insulin
type 1 diabetes
•Insulin deficiency caused by autoimmune attack on β-cells
- Islets infiltrated by activated T lymphocytes
- Failure to respond to glucose
•Hyperglycemia & Ketoacidosis:
- Elevated blood glucose & ketone levels
- Increased gluconeogenesis & reduced peripheral utilization (GLUT-4)
- Increased mobilization of FA, and oxidation by Liver
- Increased 3-hydroxybutyrate & acetoacetate
•Hypertriacylglycerolemia:
- Excess FA (not oxidised or used for ketone bodies), converted to TAG
- Also, low lipoprotein degradation by lipoprotein lipase
- Enzyme production is decreased
- Excess chylomicrons & VLDL
- Build up these compounds that can lead to adult blindless and other issues
type 2 diabetes
•Caused by a combination of insulin resistance & dysfunctional β-cells
- Insulin is not always required but can be used to control hyperglycemia
•Hyperglycemia:
-Increased hepatic production & reduced peripheral use
ketosis is minimal or absent in patient as insulin is usually present
•Dyslipidemia: imbalance of lipids
- In liver, FAs converted to TAG and secreted as VLDL
- Chylomicrons are synthesised from dietary lipids in intestine
- But, lipoprotein lipase is low, so VLDL & chylomicrons are elevated
