lipid anabolism Flashcards
lipogenesis
synthesis of fatty acids occur mainly in the liver, kidney, mammary glands, adipose tissue and brain
>mainly takes place during excess energy intake
>when excess carbohydrate is taken in … there is conversion to fatty acids and triglycerides in the liver, free fatty acids are transported in plasma bound to albumin, triglycerides formed in the liver are transported to adipose tissue by VLDL for storage
>is a reductive process
lipogenesis - simplified
dietary starch > glucose > pyruvate >acetyl Coa > fatty acids (by action of FA synthesis or B oxidation lipolysis) > triglycerides
sources of acetyl-CoA for lipogenesis
acetyl-CoA is generated in the mitochondria
>inner mitochondrial membrane is impermeable to acetyl-CoA
>citrate transports acetyl groups into the cytoplasm
-citrate is formed by condensation of acetyl-CoA with oxaloacetate
-first step in TCA cycle, when present at high concentrations, citrate is transported into the cytoplasm
what isa malonyl-CoA
a direct precursor
>activation of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (this is expressed mainly in the liver and adipose tissue)
>essential regulatory enzyme
>malonyl-CoA donates carbon atoms to new lipid
what does fatty acid synthase do?
catalyses synthesis of saturated long chain fatty acids from malonyl-CoA, acetyl-CoA, and NADPH
>is a multi-enzyme complex - exists as a single polypeptide chain with 7 distinct enzyme activities - can homodimerise through sulfhydryl cross bridges
>contains an acyl-carrier protein ACP
the 4 steps of catalysis of fatty acids synthesis
- condensation
- reduction
- dehydration
- reduction and release
lipogenesis by fatty acid synthase
fatty acids are synthesis in a cycle of reactions
>using acetyl-CoA and malonyl-CoA as precursors, one cycle of reactions adds 2 carbon atoms to the growing acyl chain
- derived from malonyl-CoA
-growing acyl chain is attached to ACP
-requires NADPH as electron donor
>when length of C16n is reached the fatty acid is released ie palmitic acid is the longest fatty acid created by fatty acid synthase
>further enzymes are required to elongate the chain further or ass unsaturated bonds if necessary
what is the control of fatty acid metabolism like
> stringently controlled
highly responsive to physiological needs
synthesis is maximal when carbohydrate and energy are plentiful and when fatty acids are scarce
acetyl-CoA carboxylase has an essential role in regulating fatty acid synthesis and degradation
regulation of acetyl-CoA carboxylase
insulin glucagon epinephrine citrate palmitoyl-CoA
insulin
signals the fed state
>stimulates the storage of fuels and synthesis of proteins
glucagon
signals the starved state
epinephrine
signals the requirement of energy ie mobilises glycogen stores
citrate
stimulates allosterically ie citrate levels are high when acetyl-CoA and ATP are abundant
palmitoyl-CoA
acetyl-CoA is antagonised by this
and it is abundant when fatty acids are in excess
synthesis of triglycerides
requires G3P
liver produces G3P from glycerol
adipose tissue produce G3P from glucose
>adipose tissue production of triglycerides only during the fed state ie insulin stimulates adipose tissue uptake of glucose
>triglycerides formation involves esterification
>liver also synthesises phospholipids, cholesterol and lipoproteins
