Metabolism of Dietary Lipids for Biochemistry

metabolism of dietary lipids in relation to medical biochemistry

1. Biochemistry
Metabolism of dietary lipids
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2. Overview:
-Water-insoluble molecules (hydrophobic).
-Some contain fatty acids.
-Fatty acids major source of energy.
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3. Overview
-Membrane-associated.
-Droplets of triacylglycerols in adipose tissues.
-Prostaglandins.
-Steroid hormones.
-Fat-soluble vitamins.
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4. Digestion
Normal diet 60 to 150 g/day.
90% of dietary lipids is triacylglycerol.
Also as dietary lipid
Cholesterol.
Cholesterol esters.
Phospholipids.
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5. Mouth & Stomach
Lingual lipase.
Gastric lipase.
Two above enzymes important for triacylglycerol
degradation in
high intake of dietary lipids (milk) in neonates
cystic fibrosis patients
Degradation at lipid/water interface.
Adults –dietary lipids are not digested in mouth and
stomach.
Emulsification of lipids via bile salts.
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6. Hormonal Control of Lipid Digestion
Hormonal control
Cholecystokinin (CCK)
Decreases gastric motility –reduces gastric emptying
Increases secretion of pancreatic fluids containing enzymes
Increases release of bile from gallbladder
Secretin
Causes secretion of watery alkaline fluid (bicarbonate) from
pancreas
Raises pH
Optimum pH for activity enzymes in lumen of intestine
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7. Lipids
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14. Triacylglycerol Degradation
Pancreatic lipase
Cleaves FA’s from carbons 1 & 3. IT CANNOT CLEAVE C 2.
Monoacylglycerol and free FA’s are products
Cystic fibrosis results in deficiency of pancreatic lipase secretion
Colipase
Binds pancreatic lipase and anchors it to lipid-water interface
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15. Hydrolysis of FA’s from Triacylglycerols
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16. Orlistat
Inhibits lipases
Reduces fat digestion
Antiobesity drug
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17. Cholesterol Ester & Esterase
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18. Phospholipid Degradation
Phospholipase A
2
Removes one FA from C-atom number 2
Product is lysophospholipid
Trypsin
Activates phospholipase A
2
Lysophospholipase
Degrades lysophospholipid
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19. Digestion of Dietary Phospholipids
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22. Absorption
Mixed micelles
Are composed of
Free long chained FA’s
Free cholesterol
2-monoacylglycerols
Bile salts
Glycerol, Short & medium chain FA’s (carbons less
than 14) do not require micelles for absorption.
They are directly absorbed from the intestinal lumen, enter
the portal vein and hence the liver.
They can be part of diet in malabsorptionsyndromes.
eg, due to reduced bile release (gall stones, cholecystectomy).
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24. Diagram of Non-Absorbable Fat
Triacylglycerol
esterified at all
carbon atoms is
non-absorbable
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26. Lipid malabsorption
Caused by
Deficiency of pancreatic lipases
Cystic fibrosis –poor digestion
Chronic pancreatitis –reduced digestion
Short bowel syndrome –reduced absorption
Pancreatic agenesis -reduced digestion
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31. Resynthesis of Triacylglycerol
(TAG’s)
Within enterocytes
Fatty acyl CoA synthesis
Triacylglycerol synthesis
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32. Fatty acid acyl CoA synthetase
(Thiokinase)
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33. Resynthesis of Triacylglycerol
2-Monoacylglycerol + 2 Fatty acyl CoA→
Triacylglycerol + 2 Co A
Enzyme-Triacylglycerol synthetase
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34. TAG Synthesis
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36. Chyle vs Chyme
Chyle–lymph fluid
Milky appearance due to presence of
triacylglycerolsand cholesterol esters
Unlike chyme–which is mass of semi-fluid secreted from
stomach to duodenum
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38. Chylomicron
There are three stages in the chylomicron's
"lifecycle":
•Nascent chylomicron
•Mature chylomicron
•Chylomicron remnant
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39. Lipoproteins and Apolipoprotein
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40. Nascent chylomicrons
The re-esterifiedtriacylglyceroliscombined
withphospholipids, cholesterolester, and
apolipoproteinB-48 forma nascent
chylomicrons.
Theseare thenreleased
byexocytosisfromenterocytesintolacteals,then
are secretedintothebloodstreamat thethoracic
duct'sconnectionwiththe leftsubclavianvein.
Nascentchylomicronsare composedprimarilyof
triglycerides(85%).
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42. Mature chylomicron
While circulating in blood, HDL
donatesapolipoprotein C-II(APOC2)
andapolipoprotein E(APOE) to the nascent
chylomicron and, thus, converts it to a mature
chylomicron. APOC2 is the cofactor
forlipoprotein lipase(LPL) activity.
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43. Chylomicron remnant
Once triglyceride stores are distributed, the
chylomicron returns APOC2 to theHDL(but
keeps APOE), and, thus, becomes a chylomicron
remnant, now only 30–50nm.
APOB48 and APOE are important to identify the
chylomicron remnant in the liver for endocytosis
and breakdown.
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50. Use of Dietary Lipids by Tissues
Triacylglycerol utilization
Adipose, skeletal muscle, heart, lung
Degraded to free fatty acids (FFA’s) & glycerol by
lipoprotein lipase (LPL).
Lipoprotein lipase present on endothelial cells of capillary bed
and hydrolyze fatty acids attached to triacylglycerols in plasma
Fate of FFA’s
Enters adipocytes and muscle
Source of ATP
Produces acetyl CoA
Transported bounded to plasma albumin to tissues
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52. Triacylglycerol Degradation –
Lipase
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53. Fate of Glycerol
Converted to glycerol 3-P in liver
Glycerol 3-P enters glycolysis or
gluconeogenesisvia dihydroxyacetone
phosphate
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54. Glycerol Metabolism
Enzyme 1 is
glycerol kinase
Enzyme 2 is
glycerol
phosphate
dehydrogenase
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55. Fate of Chylomicrons
Diameter of chylomicron particles range from 180 to 500 nm
Fate of remaining chylomicrons remnants
Binds to hepatocytes and endocytosed
Choline, ethanolamine released and re-utilized
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56. Deficiencies
Type 1 hyperlipoproteinemia
Lipoprotein lipase deficiency
Type 111 hyperlipoproteinemia
Defective endocytosis of chylomicron remnants
They accumulate in plasma
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