12 - Triacylglycerol Metabolism Flashcards
How is dietary triglycerides digested? List the relevant and important types of cells where this takes place.
Hydrolysis and re-esterification reactions involving fatty acids.
- ENterocytes (pancreatic lipase has pH optimum of 5.8-6.5 and hydrolyses sn-1 and sn-3 fatty acids.
- Hepatocytes
- Adipocytes
What is the major product of triacylglycerol digestion?
2-monoacylglycerol + 2 FFA
What is pancreatic lipase? How is it activated?
Esterase with a catalytic triad that is covered by a ‘lid’
- Activated by colipase in intestine to form a complex in presence of fatty acid and bile salt micelles
- N and C terminal regions of procolipase are cleaved to expose lipid binding domains causing a conformational change in pancreatic lipase that exposes its lipid binding domain
- Complex then binds to the micellar fat droplet
- Lid of the lipase becomes re-oriented to expose the catalytic residues to the substrate TAG
- Release of fatty acid and binding to micellualr lipid causes further recruitement of lipase/colipase complexes
Describe the steps for reassembly of triacylglycerols in enterocytes (intestine). Include the fates of different lengths of FA chains and where this takes place.
List the two relevant enzymes.
- Fatty acid and MG released by lipase digestion are taken up by the intestinal eneterocyte
- Majority of short-chain (up to C8) and medium chain (up to C12) fatty acids enter the portal blood supply direclty and are transported to the liver
- Majority of the long chain (>C12) fatty acids are re-esterified back to TAG in the enterocyte smooth endoplasmic reticulum
- TAG is packaged with apolipoprotein to form chylomicrons
- Enzymes are monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT)
The level of de novo TAG biosynthesis is regulated by what? Where is the enzyme for the first step of the pathway (formation of L-glycerol-3-phosphate) found?
Regulated by the availability of cytosolic fatty acyl-CoA and glycerol-3-phosphate derived from glycolysis
Enzyme in adipocytes: glycerol 3-phosphate dehydrogenase
Enzyme in liver: glycerol kinase
Give the steps for the de novo biosynthesis of TAG
- Glucose is converted to L-glycerol-3-phosphate through glycolysis (adipocytes) or glycerol-3-phosphate is derived from glycerol directly (in liver only)
- Glycerol-3-phosphate is conjugated with CoA via acyl transferase (twice) to form phosphatidic acid
- (PL/TAG branch point) Phosphatidic acid is converted to 1,2-diacylglycerol (DAG) via phosphatidic phosphatase (PAP) in the liver (enzyme determines how much)
- Diacylglycerol acyltransferase (DGAT) uses another CoA-SH on 1,2-DAG to form triacylglycerol
DGAT and PAP are also in ER, on cytoplasmic side of membrane
Describe the metabolism of triacylglycerols in adipose tissue. List three effects of insulin on this.
Adipose tissue synthesizes TAG when energy is plentiful and hydrolyzes it when energy is required. This is determinant on insulin.
Insulin promotes TG storage by stimulating:
- Hydrolysis of FFA from chylomicron TAG by LPL
- Uptake of glucose via membrane glucose transporters
- Stimulating dephosphorylation of the active TAG hydrolase HSL
How do glucagon and epinephrine effect TAG metabolism?
They promote TAG hydrolysis (mobilization) by hormone sensitive lipase (HSL) via a receptor coupled G protein and protein kinase cascade.
Why can’t TAG be resynthesized in adipose tissue after hydrolyzation?
Once TAG is hydrolysed to glycerol in adipose tissue, TAG cannot be resynthesized in adipose tissue because adipocytes lack the enzyme glycerol kinase (glycerol is instead transported back to the liver).
Describe the fates of metabolites from TAG metabolism in the liver
(more complicated than other tissues because metabolites have several fates)
- Glycerol can enter glycolysis via glycerol kinase reaction
- Fatty acids can be oxidized in mitochondria for energy
- Fatty acids can be synthesized de novo
- Plasma fatty acids from the diet, from adipocyte lipolysis or from de novo synthesis can be assembled into TAG
- Phospholipids can be synthesized
- TAG can be stored or secreted as lipoprotein
Reciprocal inhibition of fatty acid oxidation and biosynthetic pathways means that only one will occur even though both are possible.
List insulin’s effects on TAG metabolism in adipose tissue (4)
- Increase glucose uptake
- Increase hydrolysis of FA from lipoprotein TAG
- INcrease TAG synthesis
- Decrease TAG hydrolysis
The net effect of insulin is to promote storage of TAG in adipose tissue
List insulin’s effects on TAG metabolism in the liver (6)
- Increase glucose conversion to AcCoA (glycolysis)
- Increase TAG synthesis
- Decrease FA oxidation
- Increase FA synthesis
- Decrease gluconeogenesis
- Decrease TAG secretion as VLDL and delivery to adipose tissue
List insulin’s effects on TAG metabolism in muscles (2)
- INcrease glucose uptake
- Increase fatty acid release from lipoproteins
List glucocorticoid’s effect on TAG metabolism in adipose tissue (2)
- Decrease TAG synthesis
- Increase TAG hydrolysis
List glucocorticoid’s effect on TAG metabolism in the liver (4)
- INcrease gluconeogenesis
- INcrease FA oxidation
- INcrease glucose export
- Increase FA incorporation into TAG and secretion as VLDL for delivery to muscle for use as fuel
