BIOC 2300 Lecture Notes - Lecture 22: Glycerol Kinase, Lipoprotein Lipase, Acetyl-Coa
3 May 2018
School
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Lipids and Metabolism
March 11-14, 2016
Composition and Size of Lipoproteins
• Chlyomicrons
o Most dense <0.94
o Most triglycerides
o Apolipoproteins: apoB48, apoCII, apoE
o TG from diet to adipose
• VLDL (very low density)
o Density range: 0.94-1
o Mostly TG, some cholesterol
o apoB100, apoCII, apoE
o TG from liver to adipose
• LDL (low density)
o 1-1.063
o 50% cholesterol
o apoB100
o cholesterol from liver to periphery
• HDL (high density)
o Smallest: 1.063-1.2
o Mostly protein; 25% cholesterol
o apoA1, apoE
o cholesterol from periphery to liver
See Lipoprotein Illustration
Lipid Metabolism in Context:
• triacylglycerols contain fatty acids attached to a glycerol backbone
• fatty acids are broken down into acetyl-CoA which feeds into citric acids cycle
Triacylglycerol Synthesis
• substrates: glycerol-3-phosphate and fatty acyl CoA
• most in liver (VLDL secretion) and adipose tissue (storage)
• other tissues synthesize TG, mostly pathological
• energy storage
• TG synthesis is an “overflow” pathway.
• All nutrients can be converted to acetyl-CoA and thus, to fatty acids and TG
• There is no feedback inhibition of TG synthesis (excess nutrients are stored as TG)
• Sources for glycerol-3-phosphate:
o Liver: glycerol kinase phosphorylates glycerol glycerol-3-phosphate
o Adipose Tissue: glucoseglycerol-3-phosphate via glycolysis; de novo via
glyceroneogenesis **no glycerol kinase
o **Glycerol-3-phosphate is derived from glycerol kinase (in the liver) by
glycolysis or glyceroneogenesis
find more resources at oneclass.com
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▪ when glucose is available, DHAP is derived from glycolysis
▪ when glucose is not available, DHAP is derived from glyceroneogenesis
▪ Glyceroneogenesis=gluconeogenesis up to DHAP, then DHAP is reduced
to glycerol-3-phosphate
• If glycerol-3-phosphate is used for TG synthesis, electrons do not
enter ETC **may act as a shuttle for a source of QH2
▪ Glycerol-3-phosphate is a precursor for TG and glycerophospholipids
• Sources for Fatty acyl-CoA:
o Acyl CoA synthetase
• Fatty acids are first activated by the binding of CoA
o Fatty acid + Co-ASH + ATP Fatty acyl-CoA + AMP + ppi
o Glycerol-3-phosphate (acyltransferase) phosphatidate (phosphatase)
Diacylglycerol (acyltransferase) triacylglycerol
o All occurs in cytosol
• TG uptake into tissue for energy or storage: hydrolysis of lipoprotein TG, uptake of fatty
acids and reesterification to TG
o Chylomicrons and VLDL have a lot of triacylglycerides
o Chylomicrons transport dietary TG to adipose
o VLDL transport TG from liver to tissues
o TG are hydrolyzed in capillaries by lipoprotein lipase
o FA taken up into cells
o Glycerol remains in bloodstream
o FA are delivered to adipose for storage as TG
• Uptake of FA from Lipoprotein TG in Adipose
o Storage of dietary or liver-derived fat in adipose required hydrolysis of TG in
lipoproteins (uptake of FA and resynthesis of TG)
o In adipocyte: FA activated with CoA
o Fatty acyl CoA are esterified with glycerol-3-phosphate triacylglycerols
• Mobilization of fat stores to provide energy to the organism: hydrolysis of TG in Adipose
o TG in adipose are hydrolyzed when body requires energy
o FA and glycerol secreted into bloodstream
o Lipolysis is catalyzed by lipases: adipose triglyceride lipase (ATGL) and hormone
sensitive lipases (HSL)
o These 2 enzymes are regulated by hormones so fat stores can be mobilized
o *LPL most active after meal (when TG have to be stored), ATGL is most active
during fasting (mobilized energy stores)
o Adipose tissue cannot resuse glycerol due to absence of glycerol kinase
• Fate of Glycerol:
o Liver uses glycerol in glycolysis or gluconeogenesis depending on need
o Glycerol can be made during chylomicron uptake into adipose tissue or during
lipolysis: different metabolic situations, different hormones liver
gluconeogenesis/glycolysis can use it
o Glycerol-3-phosphate is not the same as the glycolytic intermediate glycerate-3-
phosphate
• Fate of Fatty Acids:
o Can be broken down by nearly any tissue (except brain and rbd)
find more resources at oneclass.com
find more resources at oneclass.com
