LIPID METABOLISM
Fats (Triacylglycerols)
Phospholipids acetylcholine
Sphingophospholipids sphingomyelin
Glycolipids galactosylceramide
Cholesterol
Fatty acids
Bile acids
Lipid functions • • Storage form of energy Supply essential fatty acids Structural components of cell membranes Electrical insulation Protect body from cold Mechanical protection of internal organs Metabolic regulators (hormones) Help transport fat soluble vitamins
Human pancreatic lipase (activation by colipase) Colipase is colored in blue
Emulsification
Breakdown of fats
Absorbtion
Steatorrhea Increased excretion of neutral fat Increased excretion of fatty acids Pancreatic exocrine insufficiency Intestinal pathology
Lipid resynthesis in cells of intestinal wall epithelium β-monoglyceride pathway
α-glycerophosphate pathway
Formation of chylomicrons
Lipoprotein structure
Transport lipoproteins
Fat transport
Artery section RBC Chylomicron
Dislipoproteinemia (hyperlipoproteinemia) Type I Ø Reduced activity of lipoprotein lipase (LPL) Ø Deficiency of apo. CII (LPL activator )
adipocyte Proteinkinase inactive АТP c. АМP Proteinkinase active ТАG-lipase inactive ТАG-lipase active Tissue lipase activation Glucagon Adrenalin blood Glycerol Fatty acids Oxidation in tissues
-Oxidation of fatty acids carnitine acyl transferase Rate-limiting!
Breakdown of acyl carnitin in mitochondria CAT
Dehydrogenation
Hydration
Dehydrogenation
Thiolase reaction
Propionyl-Co. A metabolism
Oxidadion of unsaturated fatty acids
α-Oxidation (nervous tissue, 20 С) -Oxidation (in pathology)
Violations of fatty acid oxidation • Hereditary defects of carnitine acyl transferase I or enzymes of carnitine synthesis • Genetic defect of dehydrogenase of fatty acids with medium chain
Synthesis of ketone bodies 2 CH 3 -CO- SCо. А Liver! - HS-Cо. А CH 3 -CO-CH 2 -CO-S-Cо. А + CH 3 -CO-S-Cо. А -Н 2 О -HS-Cо. А HOOC-CH 2 -COH(CH 3)-CH 2 -CO-S-Cо. А - CH 3 -CO-S-Cо. А CH 3 -CO-CH 2 -COOH + NАDН + Н+ - CO 2 + - NАD CH 3 -CO-CH 3 -CHOH-CH 2 -COOH
Oxidation of ketone bodies acetoacetate succinyl-Co. A-transferase succinate acetoacetyl-Co. A thiolase Myocardium Renal cortex + НS-Ко. А 2 acetyl-Co. A
Mechanism of ketosis
Lipogenesis Acetyl-Co. A transport
Lipogenesis СО 2 + АТP + biotin-enzyme carboxybiotin-enzyme + АDP + Pi carboxybiotin-enzyme + СН 3 -СО-SКо. А НООС-СН 2 -СО-S-Ко. А + biotinmalonyl-Co. A enzyme Rate-limiting!
Fatty acid synthase structure
acetyl transacylase Acetyl Co. A + ACP Acetyl-ACP + HSCo. A malonyl transacylase Malonyl Co. A + ACP Malonyl-ACP + HSCo. A (ACP = acyl carrier protein)
Formation of other fatty acids Palmitic acid 16: 0 desaturase Palmitoleic Acid 16: 1 (9) elongase Stearic acid 18: 0 desaturase Oleic acid 18: 1(9)
Regulation of acetyl-Co. A carboxylase activity
Regulation of acetyl-Co. A carboxylase activity
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