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
