Energy Production: Lipids Flashcards
Discuss the various classes of lipids
• Fatty acid derivatives
○ Fatty acids - fuel molecules
○ Triacylglycerol - fuel storage and insulation
○ Phospholipids - components of membranes and plasma lipoproteins
○ Eicosanoids - local mediators
• Hydroxy-methyl-glutaric acid derivatives - HMG (C6)
○ Ketone bodies (C4) - water soluble fuel molecules
○ Cholesterol (C27) - membranes and steroid hormone synthesis
○ Cholesterol esters - cholesterol storage
○ Bile acids and salts (C24) - lipid digestion • Vitamins - can’t be synthesised from body - come from diet
○ A, D, E, K
What type of fat molecule is the main dietary and storage lipids in the body
Triacylglycerols
Describe the structure of triacylglycerols
○ Glycerol backbone with 3 fatty acids chains attached ○ Joined by esterification
○ Hydrophobic - stored in anhydrous form (lipid droplets) - in adipose tissue
○ Utilised in prolonged exercise, starvation, during pregnancy
○ Storage/mobilisation under hormonal control (insulin and glucagon)
Where does triacylglycerol metabolism not occur
○ Does not occur in cells without mitochondria - red blood cells
○ In the brain, prefers to use glucose as fatty acids do not easily pass blood-brain barrier
Outline how triacylglycerol is metabolised into fatty acids and glycerol
○ Lipids (triacylglycerol) in diet hydrolysed in small intestine by pancreatic lipases into fatty acids and glycerol
§ Requires bile salts and protein factor called colipase
○ Recombined in small intestine and transported as triglyceride by lipoproteins (chylomicrons) to adipose tissue
§ Stored in adipose tissue as triglyceride
○ Fat mobilisation attaches triglyceride to albumin and moves it to consumer tissues to release energy through oxidation - occurs when insulin low and glucagon/adrenaline high
○ Can also directly move to consumer tissues from fatty acids and glycerol in small intestine
Outline the breakdown resynthesis process in adipose tissue
○ Glycerol-1-P added to cycle to sustain triglyceride levels
○ Combines with triglyceride -> fatty acids (+ glycerol) -> fatty acyl-CoA (+glycerol-1-P) -> triglyceride
○ During starvation, low glucose concentration so low glycerol-1-P, fatty acids released in cycle not sustained
§ Fatty acids are released as alternative fuel
State when and where fatty acid catabolism occurs
• Fatty acid catabolism - occurs in mitochondria
○ Occurs when body subject to stress (aerobic exercise, starvation, lactation)
§ Activated by adrenaline, glucagon, growth hormone, cortisol, thyroxine
§ Inhibited by insulin
○ Adipose tissue hydrolysed by enzyme hormone-sensitive lipase - lipolysis
○ Does not occur in CNS because fatty acids do not readily cross the blood-brain barrier
Describe the stages of fatty acid catabolism
- Fatty acid is activated by linking to coenzyme A outside the mitochondria
§ Fatty acyl coA synthase enzyme links fatty acid to coenzyme A
§ Requires ATP
§ Activated fatty acids do not readily cross the inner mitochondrial membrane - Transported across the inter mitochondrial membrane using a carnitine shuttle
§ Carnitine exchanges with acetyl CoA
§ Regulated - controls fatty acid oxidation
§ Inhibited by malonyl -CoA - prevents newly synthesised fatty acids from moving back into cytoplasm
§ Defects can occur in this transport system (exercise intolerance, lipid droplets in muscle) - Fatty acid cycles through sequence of ß-oxidative reactions, with C2 removed each cycle
§ Begins with a C18 stearic acid structure
§ C2 atoms converted to acetyl CoA and enters the Krebs cycle
§ FAD and NAD reduced to FADH2 and NADH and enter the electron transport chain
§ More energy derived from fatty acid oxidation than glucose oxidation
Briefly describe glycerol metabolism
○ Can be transported in the blood to the liver where it is metabolised
○ Glycerol kinase catalyses phosphorylation
○ Eventually used in triacylglycerol synthesis or glycolysis
What are the ketone bodies produced in the body
• 3 ketone bodies produced in the body - water soluble molecules
○ Acetoacetate (liver)
○ Acetone - spontaneous decarboxylation of acetoacetate
○ ß-hydroxybutyrate (liver)
How is ketone body concentration elevated
• Normal plasma ketone body concentration < 1mM
○ Starvation 2-10mM (physiological ketosis)
○ Untreated type 1 diabetes > 10mM (pathological ketosis)
§ Metabolising glucose as not taken into tissues
○ Ketoacidosis can occur with high acetoacetate and ß-hydroxybutyrate - acetone smell in breath
Outline how ketone bodies are synthesised
• Synthesised by liver mitochondria through lyase and reductase enzymes
○ Controlled by insulin/glucagon ratio
§ Low ratio - lyase is activated and reductase inhibited, producing ketone bodies
§ High ratio - lyase inhibited and reductase activated, cholesterol synthesis occurs
○ Requires fatty acids to be available for oxidation in the liver following excessive lipolysis in adipose tissue - supplies the substrate
§ Requires the plasma insulin/glucagon ratio to be low
What happens at high ketone body concentrations
• When ketone body concentration above renal threshold, excreted in urine
○ Could lead to ketonuria (abnormally large concentration of ketone in urine)
• Acetoacetate and ß-hydroxybutyrate are relatively strong organic acids
○ Could lead to ketoacidosis
• Volatile acetone may be excreted via the lungs (smell of acetone - nail varnish remover - on breath)
How do ketone bodies affect brain energy supply
- Ketone bodies conserves circulating glucose concentration for the brain by using an alternative pathway for energy
- In late starvation, proteins in muscles broken down and pyruvate resynthesize glucose to keep circulating glucose concentration constant for the brain
How is ketone body production controlled
○ Ketone body production increases NADH concentration, which can act as a end product inhibition of TCA cycle
○ Acetyl CoA concentration increases, which produces ketone bodies instead
