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Course Outlines: Lipid Family
Course Outlines: Lipid Family
1. Course
outlines
1-Lipid digestion and absorption and their errors 2. Fate of absorbed lipids 3. Lipolysis and Lipogenesis 4. Fatty acid oxidation and synthesis 5. Ketogenesis and ketolysis 6. Cholesterol and Lipiprotein metabolis 7. Fatty liver
Phospholipids Sterols (cholesterol) cholesterol esters are digested by esterase to fatty acids and cholesterol which absorbed as such As storage and transport form of metabolic fuel To keep the body temperature Source for essential FA and oil soluble vitamins To protect important organs
Challenges Lipids are not water soluble Triglycerides too large to be absorbed Digestive solution Triglycerides mix with bile and pancreatic secretions Emulsification and digestion
Minor digestion of triacylglycerols in 1. Mouth by lingual lipase 2. Stomach by gastric lipase (in infants only). Major digestion of all lipids in the lumen of the duodenum/ jejunum by Pancreatic lipases
Produced in liver, stored in gallbladder Alkaline solution composed of: Bile salts Cholesterol Lecithin Bilirubin Responsible for fat emulsification ---------------------------------------------------Mixed micelle formed by bile salts, triacylglycerols and pancreatic lipase.
Pancreatic lipase acts on triglycerides Triglycerides 2 monoglyceride + 2 fatty acids Pancreatic colipase Activated by trypsin Interacts with triglyceride and pancreatic lipase Improves activity of pancreatic lipase
Secreted from pancreas as procolipase Activated (cleaved) by trypsin Anchors lipase to the micel One colipase to one lipase(i.e., 1:1 ratio)
Produces small lipid spheres Greater surface area Lipases attack TG at 1 and 3 positions
Acidity of duodenal content (zollinger-Ellison syndrome) Deficiency of bile salts (ileal resection) Bacterial over growth Decrease intestinal cells for absorption Failure of synthesis of apoproteins (abetalipoproteinemia)
1. Steatorhoea stool fat > 5 gm per day 2. Chyluria (milky urine) Abnormal connections between lymphatics and urinary system.
I- Lipolysis
A- Definition:
- Lipolysis is the hydrolysis of triacylglycerols in adipose tissue into glycerol and fatty acids. Triglycerides Glycerol + 3 free fatty acids
B- Steps:
- Lipolysis is carried out by a number of lipase enzymes, which are present in adipose tissue. These are: 1. Hormone sensitive triacylglycerol lipase. 2. Diacylglycerol lipase. 3. Monoacylglycerol lipase.
Note
In muscle cells and adipocytes, the activity of glycerol kinase is low, so these tissues cannot use glycerol as fuel.
TG lipase is the rate-limiting enzyme in the TG degradation in adipose tissue. It is also named HSL because it is regulated by some hormones.
- In conditions where the need for energy is increased e.g.: 1- Starvation. 2- Diabetes mellitus. 3- Low carbohydrate diet.
Beta oxidation (major catabolic pathway and never occurs in the brain) Alpha oxidation Omega oxidation
Cleavage of fatty acids to acetate in tissues Occurs in the mitochondria of liver, kidney and heart Never occur in the brain Fatty acid catabolism can be subdivided into 3 stages.
Carrier: carnitine
Carnitine carries long-chain activated fatty acids into the mitochondrial matrix
step 1: Dehydrogenate step 2: Hydration step 3: Dehydrogenate step 4: Thiolytic cleavage Step 1. Dehydrogenate
Summary
one cycle of the -oxidation: fatty acyl-CoA + FAD + NAD+ + HS-CoA fatty acyl-CoA (2 C less) + FADH2 + NADH + H+ + acetyl-CoA
The product of the -oxidation is in the form of FADH2, NADH, acetyl CoA, only after Krebs cycle and oxidative phosphorylation, can ATP be produced.
-Oxidation of Myristic(C14)
Acid
Cycles of -Oxidation
The length of a fatty acid Determines the number of oxidations and the total number of acetyl CoA groups Carbons in Acetyl CoA Fatty Acid (C/2) 12 6 14 7 16 8 18 9
-Oxidation Cycles
(C/2 1) 5 6 7 8
ATP production for Myristic(14 carbons): Activation of myristic acid -2 ATP 7 Acetyl CoA 7 acetyl CoA x 12 ATP/acetyl CoA
84 ATP
II- -Oxidation:
This types of oxidation occurs in position and characterized by: 1- It is mechanism mainly for branched chain fatty acid, which is methylated at position. 2- It is specific for oxidation of phytanic acid. 3- It is minor pathway for fatty acid oxidation. 4- It occurs mainly in brain and nervous tissues.
In -oxidation, there is one carbon atom removed at a time from position. It dose not require CoASH and dose not generate high energy phosphate.
Refsums disease: This is inherited deficiency of enzymes responsible for oxidation of phytanic acid. This leads to accumulation of phytanic acid in serum and nervous tissue and produce nervous damage e.g. deafness and blindness.
-Oxidation
1. It is oxidation of terminal CH3 group of fatty acid. 2-It produces dicarboxylic fatty acids. By -oxidation, they are converted to adipic acid (6 carbons) and suberic acid (8 carbons). 2-It is a minor pathway for fatty acid oxidation and used for oxidation of long chain fatty acids.
Ketone Bodies
Formation and Utilization
Ketone bodies are: water-soluble fuels Normally exported by the liver overproduced during fasting or in untreated diabetes mellitus.
The formation of ketone bodies (Ketogenesis) Location: hepatic mitochondria Material: acetyl CoA Rate-limiting enzyme: HMG-CoA synthase
Occurs at extrahepatic tissues due to Lack of succinyl-CoA transsulfurase and Acetoacetate thiokinase in the liver.
Lipogenesis
A- Definition: - Lipogenesis is the synthesis of triacylglycerol from fatty acids (acyl CoA) and glycerol (glycerol-3-phosphate).
B- Steps:
1- Activation of fatty acids into acyl CoA:
3-Formation of TAG
Regulation of lipogenesis
After meal, lipogenesis is stimulated: - Insulin is secreted which stimulates glycolysis. Glycolysis supplies dihydroxyacetone phosphate that converted into glycerol-3-phosphate in adipose tissue, so lipogenesis is stimulated. During fasting lipogenesis is inhibited: - Anti-insulin hormones are secreted. These inhibit lipogenesis and stimulate lipolysis
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