Lipid Synthesis & Degradation Flashcards
what is the role of fats in the body?
- membrane formatin
- uptake of lipid soluble vitamins
- precursors of steroid hormones
- energy store
what is the energy content of fat in comparison to proteins and carbohydrates?
energy content is 2x/g compared to proteins and carbohydrates
when is the synthesis of fat triggered and what is the main source of it?
- when caloric intake > consumption
- cardiac muscle use fats as preferred energy source
- dietary carbohydrate is the most common source bu aa can also be used
what is the structure of fatty acids (FA)?
- chains of methyl groups with a terminal carboxyl group at one end
- id double bonds present, in cis formation
why do humans need to obtain FA in diet?
- humans unable to make double bodes at positions below position 9
- bc they cannot be made in body
where does FA synthesis occur and what does it require?
- in cytosol
- requires acetyl CoA, ATP, NADPH
how does the citrate-malate antipode system work and why do we need it?
- pyruvate is transported from cytosol to inside of mito
- converted to oxaloacetate where acetyl CoA is added to make citrate
- citrate is removed form mito and back into cytosol so acetyl CoA can be released, forming oxaloacetate again
- NADP is added to oxaloacetate to from malate which forms pyruvate when NADPH is removed
- this is done as acetyl CoA cannot pass membrane of mito
what is the first step of FA synthesis?
- acetyl CoA + ATP + HCO3- —-> malonyl CoA + ADP +Pi
- acetyl CoA (C2) has C molecule added by HCO3- with ATP to form malonyl CoA (C3)
- important, irreversible regulatory step activated by citrate and inhibited by palmitic acid
- requires vit B7
what is the structure and function of cholesterol?
- rigid hydrophobic molecule that is insoluble in H20
- important membranen component and precursor of sterols, steroids and bile salts
- transported in circulation as cholesteryl esters
what health issues can cholesterol imbalance lead to?
gallstones and atherosclerosis
describe cholesterol synthesis
-synthesised in ER (w over 30 steps involved)
- starts w activation of acetate in acetyl CoA
- major regulatory step is conversion of 3-hydroxyl-3-methyl-glutaryl CoA (HMG-CoA) to mevalonate
- cholesterol inhibits HMG-CoA reductase
- difficults to remove cholesterol by diet alone
what are the 3 steps of FA degradation?
- mobilisation (in adipocyte)
- activation (in liver cytosol)
- degradation (in liver mito)
what happens in FA mobilisation?
- GPCR activates adenylate cyclase to increase [cAMP] made from ATP, which activates protein kinase
- protein kinase activates triglyceraol lipase
- triglycerol lipase converts triacylglyceril to diacylglyceril
- diacylglycerol is broken down to glycerol and FA
what happens to glycerol formed in FA mobilisation?
- absorbed by liver
1) glycerol phosphorylated to glycerol-3-phosphate
2) glycerol-3-phosphate is oxidised by dihydroxyacetone phosphate
3) dihydroxyacetone phosphate is isomerism to gform glyceraldehyde-3-phosphate (GAP) - most GAP is used in cluconeogenesis and some goes towards glycolysis
what is FA activation?
- FA transported to liver and activated by acyl-CoA synthase in cytoplasm to form fatty acyl-CoA
- fatty acyl-CoA reacts with alcohol carnitine to form fatty acyl-carnitine
- fatty acyl-carnitine is transported across inner mito membrane by translocate
- the fatty acyl-carnitine is broken down and releases acyl to combine with CoA, remaking acyl-CoA
what is FA oxidation/degradation and where does this occur?
- β-oxidation
- mito of liver
- acyl-CoA degraded by sub sequential removal of 2C unit
what does FA oxidation produce?
-FADH2, NADH, Acetyl CoA
- FADH2 & NADH will form ATP
- Acetyl CoA will enter citric acid cycle but only in presence of glycolysis
why does FA oxidation occur in liver?
- main production of FA oxidation is to produce acetyl-CoA which can be fed into citric acid cycle for energy
- acetyl CoA can be converted to ketone bodies
in non-hepatic cells, the oxidation of palmite produces how many ATP molecules?
106 ATP molecules
what is ketogenesis
the production of ketone bodies in the metabolism of fats
describe the stages of ketogenesis
- acetyl CoA from the break down of FA is converted to acetoacetyl CoA
- acetoacetyl-CoA is converted to HMG-CoA
- HMG-CoA is converted to acetoacetate
- acetoacetate can either be reduced to 3–hydroxybutyrate or acetone
what is the fate of ketone bodies?
- acetoacetate is converted in the non-hepatic tissues back to acetyl CoA = for ATP
- major energy source for cardia muscle and renal cortex
- during starvation ro diabetes, 75% of the brain’s energy derived from acetoacetate
- [ketone] increases as [food intake] decreases
how does insulin regulate fat metabolism?
- increases glycolysis in liver
- increases FA synthesis in liver
- decreases β-oxidation
- increases triglycerides in adipose tissue
how do glucagon and adrenaline regulate fat metabolism?
increase triglyceride mobilisation
what is formed in the breakdown of triglycerides?
glycerol
what is the use of triglyceride degradation?
- in liver: for synthesis of glucose in gluconeogenesis
- in muscle: used for ATP production in OXPHOS and glycolysis
why are free FA transported into inner mito matrix?
enzymes required for degradation of FA are in inner mito matrix
what is the importance of carnitine?
- deficiency causes muscle weakness and even death
- required as FA degradation cannot happen without it
