FORM & FUNCTION (Fat Synthesis) Flashcards
fatty acids (FA)
-simplest form of lipids
-long chains of aliphatic hydrocarbons with a carboxylic acid
-saturated (no double bonds) vs. unsaturated
-basic components of many things
-rarely ‘free’ (FFAs) in biological systems
*usually esterfied in storage
FAs basic components of
-triglycerides (fat storage)
-lipoproteins (fat transporter molecules)
-glycerolphospholids (membrane constituents)
-ketone bodies (soluble fat for energy)
-cholesterol (hormone, vitamin, bile acids)
-eicosanoids (signalling molecules)
FA stored
-commonly esterified
-stored as triacylglycerol (3FFA + 1 glycerol)
-can not form end to end like CHO
Triacylglycerol (triacylglycerol)
-as close as lipids come to form polymers
-cannot join end to end
-can aggregate into large globules=storage depot for fat
FFA
-free FA
-fatty acid not attached to glycerol (in an ester linkage)
FA synthesis
-starting material is acetyl-CoA
*liver is major site of FA biosynthesis
1. Converts acetyl-CoA to FA
2. Exports them for storage in adipose
Sources of Acetyl-CoA
-amino acids
-CHO
-lipid
*excess of these are synthesized and stored as fat
Acetyl-CoA translocation
-FA synthesis takes place at the cytoplasm
-Acetyl-CoA is found in mitochondria
*utilize citrate shuttle to bring acetyl-CoA back into the cytoplasm
-change Acetyl-CoA to citrate, through citrate shuttle then back to Acetyl-CoA
Carboxylation reaction
-first and rate-limiting step of of FA synthesis
*catalyzed by Acetyl-CoA carboxylase (ACC)
-reaction requires a carboxybiotin group that is formed by biotin carboxylase
*first intermediate product is Malonyl-CoA
Acetyl-CoA carboxylase (ACC)
-first step is physiologically irreversible
-allosterically and hormonally controlled
ACC allosterically controlled
-activated by citrate: starting material
-inhibited by palmitoyl-CoA: end product
*self regulated
ACC hormonally controlled
*reversible phosphorylation
-dephosphorylated: active
>insulin (high nutrient state): protein phosphatase 1
-phosphorylated: inhibited
>glucagon/E, high AMP (low energy state): AMP kinase
Fatty acid synthase (FAS)
-start with 1 acetyl-CoA + 1 malonyl-CoA: each attached to FAS
-cycle repeats (6x) until FA synthesis is complete, adds 1 malonyl-CoA (2C) each time
Palmitate (16:0)
-common product of fatty acid synthesis
-basic precursor for other fatty acids
*free FA are esterified to from triglycerides (can form lipid bilayers: structural constituents of the cell)
Basic FA precursor: modifications
- Desaturase: addition of double bonds
- Elongase: extension beyond 16 carbon
FA biosynthesis summary
-excess nutrients (mostly CHO) are utilized as precursors
-regulated by acetyl-CoA carboxylase (hormone sensitive)
-palmitate (16:0) is the basic precursor for many FA derivatives
*all taking place in liver
Triglycerides (TG)
-FFA are stored as TGs
-begins with glycerol-3-phosphate
-addition of 3 FA acyl-CoA to produce TGs
Glycerol-3-phophate
-part of storing FFA as TGs
1. Phosphorylation of glycerol by glycerol kinase (liver & kidney)
2. Reduction of dihydroxyacetone phosphate from glycolysis (adipose)
TG transport
-TG are mainly synthesized in the liver
-insoluble
-requires interaction with lipoprotein complexes to transport in plasma & between tissues
Classes of lipoproteins
- Chylomicrons (CM)
- Very low density lipoproteins (VLDL)
- Intermediate/low/high density lipoproteins
chylomicrons
-transports exogenous fat (from diet)
VLDL
-transports endogenous fat (made by body)
IDL, LDL, HDL
-breakdown products of VLDL&CM
Lipoprotein structure
-hydrophilic head and proteins make lipoproteins soluble