Session 7 - Energy Production: Lipids Flashcards
What are the 3 classes of lipids
1) Fatty acids (Triglycerides)
2) HMG acid derivatives (Ketone bodies)
3) Vitamins (A,D,E and K)
What controls Triglyceride utilisation and storage and when might this change?
- Storage/mobilisation is under hormonal control (insulin and glucagon for example)
- Utilised in prolonged exercise, starvation and during pregnancy
How are fatty acids absorbed?
1) converted back to triacyl glycerides (TAGs) in GI tract
2) Packaged into lipoprotein particles
3) Chylomicrons
4) Released into circulation via lymphatics
5) Carried to adipose tissue
6) stored as TAG
7) releases as fatty acid when needed
8) Carried to tissues in blood via an albumen-fatty acid complex
Summarise the basics of fatty acid catabolism
- Occurs in the mitochondria
1) FA is activated by linking with CoA outside of the mitochondria
2) Transported across the mitochondrial membrane using the carnitine shuttle
3) FA cycles through sequence of oxidative reactions, with 2C removed each cycle
How does the carnitine shuttle work and why is it needed?
Fatty-acyl-CoA doesn’t readily cross the mitochondrial cross the inner mitochondrial membrane.
1) Acyl-CoA converted to Acyl carnitine and transported across membrane
2) Acyl carnitine to Acyl-CoA and carnitine shuttled back across membrane
Outline the key features of Beta oxidation (fatty acid catabolism)
-Each cycle 2 carbons are removed and 2 carriers are reduced
- Each cycle produces acetyl-CoA which is fed into the TCA cycle
-More energy derived from FA oxidation than glucose oxidation
-No substrate level phosphorylation (yet ATP is invested when activating with CoA)
Stops in absence of O2
Glycerol Metabolism
Glycerol is metabolised in the liver
-1 of 2 paths: form DHAP (an intermediate in glycolysis) or TAG synthesis
Outline some functions of Acetyl-CoA
Important in both Catabolism and Ananbolism
- Form TAGs and Phospholipids
- Energy production (CO2 and energy)
- Ketone production
- Steroid hormones (from cholesterol)
Name the 3 ketones produced in the body
- Acetoacetate
- Acetone (spontaneous non-enzymatic breakdown of acetoacetate)
- Beta- hydroxybutyrate
What is the difference between physiological and pathological ketosis? What are the standard ketone levels?
- Normal Plasma Ketone body Conc. = <1mM
- Starvation (Physiological Ketosis) = 2-10mM
- Untreated Type 1 Diabetes (Pathological Ketosis) = >10mM
Where are ketones synthesises and how does this occur?
Ketones bodies are synthesised in the liver by liver mitochondria
1) acetyl-CoA is converted to HMG-CoA via synthase
2) The enzyme Lyase converts HMG-CoA to Ketones
How do statins act to reduce cholesterol?
Statins inhibit the enzyme HMG-CoA reductase this reduces the conversion of HMG-CoA to mevalonate and ultimately cholesterol
How is ketone synthesis regulated by the insulin/glucagon ration?
Fed state - Insulin levels are high. This inhibits lyase and activates reductase. This reduces ketone production and increases cholesterol production
Starvation state - Insulin levels are low. This activates lyase and inhibits reductase which increases ketones synthesis and inhibits cholesterol production
What happens in early and late starvation?
Early - Lipolysis in adipose tissue and ketogenesis in the liver supply muscles with ketones. This allows circulating glucose to be used in the CNS and Brain
Late (and diabetes) - Same use of ketones in muscles only gluconeogenesis of muscle protein is used to supply the brain with glucose
What are the key points about ketones and their metabolism?
- Water soluble
- Permits relatively high plasma concentrations
- Alternative substrate
- Volatile acetone may be excreted via the lungs (this is characteristic of someone starving or undergoing ketosis)
