Lipid Metabolism Flashcards
Beta-oxidation
Goes from fatty acids to a 2C acetyl-CoA Synthesis is the reverse of this Will cost some energy to build a FA The ACC will enter the CAC Major source if energy production during fasting
Fatty acid synthesis overview
Acetyl-CoA is the source of all carobs and comes from carbs and proteins NADPH and ATP required Mostly in adipose and liver Occur during the fed state FA--->TG
Citrate role in FA synthesis
Citrate shuffle acetyl-CoA out of the mitochondria for fatty acid synthesis in the cytosol
Acetyl-CoA is made inside the mitochondria, when we have excess we can use it to make FA
Citrate piles up in the mitochondria and exits it
ATP used to convert it back to ACC and OAA
Convert back to pyruvate which reenters mito and also NADPH is created for FA synthesis
Initial priming reactions for FA synthesis
FA is a very large multi enzyme complex
Growing chain held by 2 different arms which are acyl carrier proteins
Grows by 2C acetyl units but they are added as 3C malonyl units
Grows from COOH end, CH3 is added first
Reduction and chain elongation in FA synthesis
Adding 2C at a time by an acetyl group Use malonyl 3C to add the 2C One is removed by decarboxylation and NADPH is used to reduce Cycle repeated Synthesis stops at 16 or 18 carbons Elongases extend FA by two carbons
Remodeling
Allows our body to control the FA composition
Relative amounts of omega3 and omega6 cannot be adjusted
Desaturation of fatty acids
Desaturates add double bonds
Lack desaturates to insert omega3 and 6 double bonds
These must be obtained from the diet and are essential fatty acids
We have them but we can’t make them
Control of FA synthesis
Acetyl-CoA carboxylase is rate limiting control point
Acetyl-CoA + CO2 —-> malonyl-CoA
Uses ATP
Hormonal control of FA synthesis
Fasting state: glucagon, turn OFF FA synthesis. Inactivated acetyl-CoA carboxylase (protein kinase A)
Fed state: insulin, turn ON FA synthesis. Activates acetyl-CoA carboxylase (protein phosphatase)
AMP-PK regulates FA synthesis
AMP-PK phosphorylates and inactivated acetyl-CoA carboxylase
AMP-PK is active when AMP is high (fasting and exercise), decreases FA synthesis and decreases beta-oxidation
AMP-PK is inactive when glucose concentration is high (fed storage, type II diabetes), increased fatty acid synthesis and decreased beta oxidation
Increased FA and TG synthesis contributes to hyperlipidemia seen in type II diabetes
Synthesis of triglyceride
Glycerol phosphate can come from glycerol or DHP
creates a diglyceride, add a third FA to make a triglyceride fat
Allosteric control of FA synthesis
Citrate (acetyl-CoA) in cytosol activate palmitate(end-product) which feedback inhibits
Altered citrate levels may be involved in hyperlipidemia in type II diabetes
Overview of TG/FA catabolism
FA mobilized from adipose tissue by hormone sensitive lipase action on TG
Complexed with albumin for transport in blood to tissues
Activated to FA-CoA in cytosol (thiokinase)
Carried not mitochondria (carnitine)
Fatty acids are beta oxidized back to acetyl-CoA using some ATP
Acetyl-CoA oxidized through CAC to make ATP
Major energy sources during fasting and stress/exercise
Glucagon during FA catabolism
Fasting state
Glycogen breakdown and gluconeogenesis in the liver
FA mobilization (adipose) and beta oxidation
FA—>TG—>ATP
Ketone body production: excess ACC during prolonged fasting or starvation can be used for energy. OAA supplies are short
Hormonal control of TG hydrolysis
Fasting state: glucagon, protein kinase is active which makes hormone sensitive lipase active as well. Use this to breakdown TG to free FA which spill out into the blood
Fed state: make it stop, make HSL inactive and FA are made
Oxidation of fatty acids
FA from blood are taken up by cells
FA need to be activated or primed for metabolism in the cytosol
Activated FA needs to get inside the mitochondria, site of oxidation
Addition of CoA to make it an activated fatty acid, uses thiokinase
Carnitine
Carries FA into the mitochondria
Moves activated fatty acid from the cytosol
Transferase transfers the activated FA to carnitine
Pulls it into the inner mito matrix where it is beta oxidized
Acetyl-CoA dehydrogenase
Converts the activated fatty acid (FA acetyl-CoA) and adds a double bond to make the unsaturated fatty acyl-CoA
Energy yield for FA oxidation
5 ATP for each turn of the cycle
Costs some energy to temporarily store acetyl-CoA as FA but you get a good bit back during beta oxidation
Lots of ATP from oxidation of ACC through CAC
Regulation of FA oxidation
Rate of entry of FA into cells depends on The concentration of FA in the blood
Malonyl-CoA inhibits carnitine palmitoyltransferase: FA syntheis, decreased FA into mitochondria, decreased beta oxidation
No FA synthesis during fasting, HSL in adipose tissue, FA mobilized and oxidized
Ketone bodies
Important energy fuel in special circumstances
Prolonged fasting or starvation, untreated diabetes
In liver mitochondria: excess ACC from beta ox of FA during prolonged fasting
Interrelationships of ketone bodies
Ketone bodies are synthesized in the liver mito from mobilized FA, can serve as energy substrates in many tissues
Includes the BRAIN, heart and skeletal muscle
FA does not cross the blood brain barrier, but water soluble ketone bodies do. During prolonged starvation, they can supply up to 70% of the brains energy needs.
Acetoacetate can be turned into acetone or beta hydroxybutyrate
Utilization of ketone bodies
Catabolism requires acetoacetate:CoA transferase and a thill ate
Transferase presents in the mitochondria of all tissues except the liver, thus the liver cannot use ketone bodies for energy
Enzymes are low in brain but induced by starvation
