lipid synthesis and degradation Flashcards
what essential roles do fats play in the body?
βa role in membranes
βuptake of lipid soluble vitamins
β as precursors of steroid hormones
βenergy store
what is the energy content of fat in comparison to proteins and carbohydrates?
βThe energy content of fat per gram is over twice that of either carbohydrates or proteins, making an important energy source.
when is the synthesis of fat triggered and what is the main source of it?
βwhen our caloric intake exceeds that of consumption, the excess is laid down as fat.
βSome tissues, such as cardiac muscle, use fats as their preferred energy source.
βdietary carbohydrate is the most common source, although amino acids can also be used.
what is the structure of fatty acids?
βThey are chains of methyl groups, with a terminal carboxyl group at one end.
βIf double bonds are present, it is in a cis formation.
why do humans have to obtain some fatty acids from diet?
βHumans are unable to make double bonds at positions less than position 9.
βThatβs why there are βessentialβ fatty acids that we have to obtain from our diets, as they cannot be made in our bodies.
what makes up the majority of fatty acids made ?
βPalmitic acid (C16) makes up the majority of fatty acids made. If a different number of carbons is required, there are enzymes that will modify it.
where does fatty acid synthesis take place and what does it require?
β in the cytosol of hepatocytes
βAcetyl-CoA
β NADPH
β ATP It involves the sequential addition of 2 carbon units derived from Acetyl-CoA.
how does the citrate-malate antiport system work and why do we need it?
βPyruvate is transported from the cytosol to the inside of the mitochondrion.
β it is converted to oxaloacetate, where Acetyl CoA is added to it to create citrate.
β the citrate is brought out of the mitochondrion back into the cytosol, an acetyl CoA molecule is released from it, turning it back into oxaloacetate.
βThen, it is converted to malate (add NADP), followed by pyruvate once again (remove NADPH) (additional NADPH is provided by the pentose phosphate pathway).
βThis is done to transport acetyl CoA outside of the mitochondrion as it canβt pass through the membrane.
what is the first step of fatty acid synthesis?
βAcetyl-CoA + ATP + HCO3- ββ-> Malonyl-CoA + ADP + Pi
βacetyl-CoA (2C) has a carbon molecule added to it by HCO3-, using ATP, changing it to Malonyl-CoA (3C).
βIt is an important, irreversible, regulatory step activated by citrate (positive feedforward) and inhibited by palmitic acid (negative feedback).
βrequires the vitamin Biotin (vitamin B7).
what is the structure and function of cholesterol and how is it transported?
βrigid, hydrophobic molecule that is virtually insoluble in water.
βIt is an important membrane component, and a precursor of sterols, steroids and bile salts.
βIt is transported in the circulation as cholesteryl esters. It canβt be oxidised to O2 or H2O, so it provides no energy.
what health issues can cholesterol imbalance cause?
βcholesterol imbalance can lead to significant health issues, such as gallstones and atherosclerosis.
describe cholesterol synthesis
βCholesterol is synthesised in the ER (with over 30 steps involved).
β It starts with the activation of Acetate in Acetyl-CoA.
βThe major regulatory step is the conversion of 3-hydroxyl-3-methyl-glutaryl CoA (HMG-CoA) to Mevalonate.
βCholesterol inhibits HMG-CoA reductase, an enzyme involved in its own synthesis.
βdifficult to remove circulating cholesterol by diet alone as endogenous synthesis is increased.
what are the three steps of fatty acid degradation?
βMOBILIZATION
βACTIVATION
βDEGRADATION
what happens during fatty acid mobilization?
βA G-protein coupled receptor activates Adenylate Cyclase that increases the amount of cAMP made from ATP, which, in turn, activates Protein Kinase.
βThis Protein Kinase activates Triacylglycerol Lipase.
βThis converts Triacylglycerol to Diacylglycerol. The Diacylglycerol is then broken down into Glycerol and Fatty Acids.
what happens to the glycerol mobilized in Fatty Acid Mobilisation?
βabsorbed by the liver.
β1) Glycerol is phosphorylated to Glycerol-3-Phosphate.
β2) Glycerol-3-Phosphate is oxidised by Dihydroxyacetone Phosphate.
β3) Dihydroxyacetone Phosphate is isomerised to Glyceraldehyde-3-Phosphate (GAP).
βThe majority of GAP goes towards GLUCONEOGENESIS, and a bit of it goes towards GLYCOLYSIS.
what is fatty acid activation?
βfatty acids are transported to the liver and activated by Acyl-CoA Synthase in the cytoplasm.
βThe Acyl-CoA produced is transported across the inner mitochondrial membrane bound to the alcohol Carnitine.
how are fatty acids activated so they can cross the membrane?
βIn the cytoplasm, the acyl-CoA will react with carnitine to give acyl-carnitine, which can then be transported across the membrane through the action of the enzyme Translocase.
βThe acyl-carnitine is then broken down back into carnitine, releasing the Acyl to combine with the CoA, remaking acyl-CoA in the mitochondria.
βThis allows the molecule to get across the membrane.
what is fatty acid oxidation and where does it occur?
βIt occurs in the mitochondria of the liver.
βAcyl-CoA is degraded by sequential removal of two carbon units
what does fatty acid oxidation produce?
βThis produces FADH2, NADH and Acetyl-CoA. The FADH2 and NADH form ATP.
βThe Acetyl-CoA ( from Ξ²-oxidation) will enter the citric acid cycle, but only in the presence of glycolysis.
why does fatty acid oxidation occur in the liver?
βIn the liver, the main production of fatty acid oxidation is for generation of Acetyl-CoA which can be fed into citric acid cycle to generate energy,
βACoA tends to be converted to ketone bodies.
how many ATP molecules are produced from the oxidation of palmitate?
β106 ATP molecules.
what are the steps in ketogenesis?
βAcetyl-CoA from breakdown of fatty acids is converted to Acetoacetyl-CoA
β Acetoacetyl-CoA is converted to HMG-CoA
βHMG-CoA is converted to Acetoacetate Acetoacetate can be reduced to 3-Ξ²-Hydroxybutyrate or non-enzymatically to Acetone.
βThese are the three ketone bodies and the two former ones are the important ones.
what is the fate of ketone bodies?
βThe acetoacetate is converted in the non-hepatic tissue back to Acetyl-CoA, this can then be used to generate ATP.
βKetone bodies are a major energy source for cardiac muscle and renal cortex.
βDuring starvation or diabetes, 75% of the brains energy is derived from acetoacetate
βthe production of ketones increases with decreased food intake.
how does insulin regulate fat metabolism?
βincreases glycolysis in the liver
βincreases fatty acid synthesis in the liver
β increases TG in adipose tissue
β decreases Ξ²-oxidation
how do glucagon and adrenaline regulate fat metabolism?
βincrease TG mobilization
How does Palmitate get generated from Fatty Acid Synthesis?
βEach cycle leads to the sequential addition of 2 carbons.
βSo 6 cycles needed to generate 16C Palmitate Fatty Acid.
How are the intermediates linked in Fatty Acid Synthesis?
βthe intermediates in this reaction are covalently linked to ACP.
How are the enzymes required for Fatty Acid Synthesis organised?
βAll enzymes required form a multi-functional complex called Fatty Acid Synthase. This exists as a dimer.
What is the importance of Carnitine?
βcarnitine deficiency can cause muscle weakness or even death.
βas fatty acid degradation cannot occur without it.
What inhibits fatty acid transport into the Inner Mitochondrial Matrix and how?
βThe transport is also inhibited by malonyl-CoA, which is a step in the synthesis of fatty acids.
β if it builds up, we will be moving towards synthesis, meaning this degradation transport process is inhibited.
Why are FFA transported into the Inner Mitochondrial Matrix?
The enzymes that break down fatty acids are present in the Inner Mitochondrial Matrix.
