MM2 Flashcards
During low intensity exercise, the major fuel source is:________
During high intensity exercise, the major fuel source is:________
- Plasma FFA
- Muscle glycogen
(2.1)
- The “Crossover” concept of shift from fat to carbohydrate metabolism as exercise intensity increases occurs because:
- At the same intensity, a shift from carbohydrate to fat metabolism as duration increases occurs because:
- Rate of ATP production from glucose is faster than fat
- Recruitment of different muscle fibre types
- Increasing plasma adrenaline levels
- reduced glucose/glycogen availability
- increased rate of lipolysis
(2.1)
Muscle glycogen breakdown is regulated by:
- Catecholamines
- Calcium
- AMP, Pi
- Substrate availability
(2.1)
TorF
Muscle glucose uptake is inversely proportional to muscle glycogen availability.
T
2.1
Liver glucose production is dependent on exercise and duration.
- What is the major source of glucose early in exercise and during intense exercise?
- What contributes during prolonged exercise when liver glycogen is low?
- Glycogenolysis
- Gluconeogenesis
(2.1)
What are the major regulatory hormones during exercise? What is its main action on: - Insulin - Glucagon - Adipose tissue - Liver
Catecholamines
- Decreases insulin
- Increases glucagon
- Increases lipolysis to increase plasma FFA
- Increases glycogenolysis to maintain blood glucose
(2.1)
Within exercising muscle cells, what controls metabolic responses?
AMPK, activated by low energy balance (decreased ATP, increased AMP)
Main actions are:
- Increases glucose uptake via increased GLUT4 translocation
- Increases fatty acid oxidation by inactivating ACC
- AMPK increases the expression of genes involved in expression of enzymes involved in processes for long-term adaptations to exercise eg increased mitochondria, increased IMTG and increased vascularisation
(2.1)
List all the sources of ATP during exercise.
- ATP stores within the muscle
- Phosphocreatine
- Glucose/ Glycogen
- Lipids
- Protein (extreme circumstances)
(2.1)
Describe the two phases of Xenobiotic metabolism
Phase 1 reactions: insertion of a reactive group to make drug more polar, permitting conjugation. Includes oxidation, reduction, hydrolysis. This can detoxify the substance or convert it into a toxin. Require cytochrome P450.
Phase 2 reactions: conjugation- substance is conjugated with a hydrophilic molecule so that it is water soluble and can be excreted. At this point it will have lost biological activity.
(2.2)
Where is Ctyochrome P450 found?
Smooth ER of liver and lungs
2.2
Describe in broad terms the cytochrome P450 cycle:
- Substrate binds near the heme-iron active site on the P450 enzyme
- series of reduction and oxidisation steps
- product is released now with a reaction oxygen group attached to- primed to be conjugated in phase 2 reaction of xenobiotic metabolism.
(2.2)
what is the clinical significance of the fact that xenobiotic metabolising enzymes (ie Cyt P450) are inducible by xenobiotics?
- The enzymes increase their expression rapidly in response to either their own substrates or other xenobiotics.
- More cytP450 enzymes means more effective drug metabolism
- Development of tolerance to drugs, requiring increase in dosage over time.
(2.2)
Ethanol metabolism
- list the two steps of ethanol metabolism
- Which is the rate limiting step of ethanol metabolism?
- At what rate does blood alcohol concentration decrease by every hour?
- Ethanol to acetalaldehyde catalysed by Alcohol Dehydrogenase (ADH), in cytosol. Then acetalaldehyde to Acetate catalysed by aldehyde dehydrogenase (ALDH), in mitochondria. The acetate is converted to acetyl CoA which goes to TCA cycle for ATP production.
- Step 1 is rate limiting. Note ADH has low Km, so the enzyme is saturated after one drink
- ~0.15g/L every hour. Note this rate is constant because the enzyme ADH itself can’t be upregulated. But you can have increased expression of this enzyme depending on genetic variations- leads to differences in alcohol tolerance.
(2.2)
Accumulation of toxic acetyladehyde after 1-2 drinks leads to what effect (particularly in East Asians)?
Oriental flush- vasodilation, tachycardia and nausea. Due to dominant negative genetic variants of ALDH.
(2.2)
What catalyses the alternative pathway for alcohol metabolism?
In whom is this pathway more important?
CytP450
Alcoholics as alcohol induces P450 synthesis
(2.2)
Describe the two key consequences of excess alcohol metabolism leading to fatty liver disease?
- Alcohol metabolism depletes NAD+ and produces excess AcetylCoA, NADH and ATP which interfere with normal metabolic processes.
1. depletion of NAD+ required for beta oxidation means there is less fatty acid oxidation leading to increase in triglyceride synthesis in the liver
2. Decreased formation of VLDL due to protein deficiency in alcoholics and toxic liver damage. - net effect is accumulation of TAGs in liver
(2. 2)
Outline the use of FITT-Pro in the prescription of exercise.
The acronym FITT-Pro describes the domains that should be included when prescribing exercise, namely:
- Frequency
- Intensity
- Type
- Time
- Progression
(2.1)
Name the stages of liver damage and what generally occurs in each stage
- healthy liver
- Steatosis- fatty liver disease
- accumulation of hepatic lipids
- key reversible stage with lifestyle intervention
- also includes NAFLD, strongly linked with obesity - Steatohepatitis
- fat accumulation, inflammation and some fibrosis
- includes NASH - Cirrhosis
- hepatocytes degenerate and are replaced by fibrous tissue
- disease is non-reversible - can progress to hepato-cellular carcinoma
(2. 2)
What initiates inflammation in the liver in the steatohepatitis stage of liver damage?
What is a Kupffer cell?
Inflammation initiated by resident hepatic macrophages- Kupffer cells.
Kupffer cells recruit monocyte derived macrophages to the liver. The inflammatory response destroys hepatocytes and replaces them with ECM and fibrosis.
(2.2)
List key complications of Liver cirrhosis due to impaired liver functions
- Fasting hypoglycaemia
- prolonged clotting time
- oedema
- hyperammonaemia
- fetid breath
- alcohol intolerance
- jaundice
(2.2)
Name the main treatment options for FLD
- Lifestyle modifications
- Metformin: increases hepatic fatty acid oxidation through AMPK activation
- Statins
- Liver transplant once cirrhosis develops
(2.2)
