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LIPID METABOLISM

BASIC LIPID FUNCTION


* BUILDING BLOCKS FOR BIOLOGICAL MEBRANES
(PHOSPHOLIPIDS, GLYCOLIPIDS, CHOLESTEROL)
* STORAGE OF BIOLOGICAL ENERGY, INSULATION
(TRIACYLGLYCEROL)
* DIGESTION OF DIETARY FAT (BILE SALTS)
* STEROID HORMONES
* INTRACELLULAR MESSENGER
EXAMPLES OF LIPID STRUCTURES

DIGESTION OF DIETARY FATS


* DUODENUM: DIETARY FATS ARE EMULSIFIED BY BILE
SALTS.
* SMALL INTESTINE: EMULSIFIED FATS ARE HYDROLYZED
BY PANCREATIC LIPASE, PHOSPHOLIPASE A2, CHOLESTEROL
ESTERASE.
* MAIN PRODUCTS: 2-MONOACYLGLYCEROL, FFA,
GLYCEROL, LYSOPHOSPHOLIPID, FREE CHOLESTEROL.

ABSORPTION OF DIETARY FATS


* PRODUCT OF LIPID DIGESTION AND FAT SOLUBLE
COMPOUNDS (VITAMINS), BILE SALTS ARE COMBINED TO
FORM MICELLES, AND TAKEN UP BY ENTEROCYTES.

DIETARY FATS ARE PACKAGED BY ENTEROCYTE INTO


CHYLOMICRON (LIPOPROTEIN)  BY EXOCYTOSIS INTO
LACTEALS  THORACIC DUCTS  BLOODSTREAM VIA LEFT
SUBCLAVIAN VEIN.

STRUCTURE OF LIPOPROTEIN.
FATTY ACID METABOLISM

FATTY ACID SYNTHESIS


* THE PROCESS OCCURS IN THE BRAIN, LIVER KIDNEY,
LUNG, ADIPOSE TISSUE AND LOCATED IN CYTOPLASM.
* IT IS ACTIVE WHEN MITOCHONDRIAL CITRATE AND ATP
CONCENTRATION ARE HIGH.
- INITIAL STEP: ACTIVATION OF ACETYL-CoA CARBOXYLASE;
acetyl –CoA + CO2 + ATP malonyl-CoA + ADP +Pi.
- COENZYME : BIOTIN.
- ELONGATON STEP:
- ENZYME: FATTY ACID SYNTHASE: A LARGE MULTI-
ENZYME COMPLEX THAT CATALYZES THE ADDITION OF
TWO-CARON UNIT IN ASEVEN-STEP CYCLE, REQUIERING
NADPH AS COENZYME.
- TERMINATION STEP: WHEN PALMITIC ACID IS PRODUCED,
THE PATHWAY IS STOPPED BY THIOESTERASE.
* ADDITION TO AND MODIFICATION OF PALMITATE 
SYNTHESIS OF MANY STRUCTUALLY DISTINCT FATTY ACIDS.
- ELONGATION OF PALMITATE OCCURS BY ADDITION OF
FURTHER ACETATE UNITS IN THE ENDOPLASMIC
RETICULUM AND MITOCHONDRIA.
- DESATURATION OR THE CREATION OF DOUBLE BONDS
FOR SYNTHESIS OF UNSATURATED FATS IS PERFORMED BY
MIXED-FUNCTION OXIDASES IN THE ENDOPLASMIC
RETICULUM.

* STORAGE AS TRIACYLGLYCEROL IN CYTOPLASM


REQUIRES ACTIVATION OF THE FATTY ACID BY
CONVERSION TO ACYL-CoA WITH GLYCEROL 3-PHOSPHATE
(REQUIRES GLYCEROKINASE, WHICH IS NOT FOUND IN
ADIPOSE TISSUE).
FATTY ACID OXIDATION
* MOBILIZATION OF FAT STORES IN ADIPOSE TISSUE
ALLOWS FATS TO BE BURNED TO PRODUCE ENERGY VIA
FATTY ACID OXIDATION.
- THE INITIAL STEP TO RELEASE FATTY ACIDS IS
TRIACYLGLYCEROL HYDROLYSIS BY HORMONE SENSITIVE
LIPASE (MAINLY PRESENT IN ADIPOSE TISSUE) WHICH IS
REGULATED BY HORMONES (GLUCAGON & EPINEPHRINE
STIMULATE AND INSULIN INHIBITS LIPASE ACTIVITY).

- FFA AND GLYCEROL ARE RELEASED INTO BLOODSTREAM


(FFA IS TAKEN UP BY THE TISSUE TO PRODUCE ENERGY VIA
BETA-OXIDATION AND GLYCEROL IS TAKEN UP BY THE
LIVER TO BE PHOSPHORYLATED INTO GLYCEROL-3-
PHOSPHATE, THEN CAN ENTER GLYCOLYSIS OR
GLUKONEOGENESIS.
* HEPATIC TG LIPASE DEGRADES TG FROM LIPOPROTEIN
REMNANTS PREVIOUSLY ENDOCYTOSED BY THE LIVER.

*BEFORE OXIDATION CAN BEGIN, THE FATTY ACIDS MUST


BE ACTIVATED BY ACYL-CoA SYNTHASE
fatty acid + CoA + ATP  fatty acid -CoA + AMP + PPi

* LONG CHAIN FATTY ACIDS MUST BE TRANSPORTED INTO


THE MITOCHONDRIAL MATRIX BY CARNITINE SHUTTLE
FOR BETTA OXIDATION TO BE OXIDIZED TO PRODUCE
ENERGY.
*THE REACTION OF BETA-OXIDATION IS TO CLEAVE FATTY
ACID IN A SERIES OF CYCLE, EACH OF WHICH SHORTENS
THE CHAIN BY 2 CARBON.
- 2 OXIDATIVE STEPS AT EACH CYCLE, PRODUCING 1 FADH2
AND 1 NADH.
- THE CARBONS OF EVEN-CHAINED FATTY ACID END UP
PRODUCING A NUMBER OF ACETYL-CoA IN THE FINAL STEP.
- UNSATURATED FATTY ACIDS CAN BE METABOLIZED
THROUGH BETA-OXIDATION, REQUIRING ADDITIONAL
ENZYMES; BUT IN EACH DOUBLE BOND PRODUCE 2 ATP
LESS THAN SATURATED FATTY ACID.
METABOLISM OF KETONE BODIES
* 3 KETONE BODIES : ACETOACETATE, BETA-HYDROXY
BUTIRATE AND ACETONE.
* KETOGENESIS OCCURS ONLY IN THE MITOCHONDRIA OF
THE LIVER CELLS, AND ACTIVE WHEN ACETYL-CoA LEVELS
EXCEED THE NEEDS OF THE ORGAN FOR USE IN ENERGY
PRODUCTION.
* KETONE BODIES PRODUCED IN THE LIVER ARE RELEASED
INTO BLOODSTREAM TO BE TAKEN BY EXTRAHEPATIC
TISSUE TO PRODUCE ENERGY.
CHOLESTEROL METABOLISM
* A SYNTHESIS OF CHOLESTEROL OCCURS IN THE
CYTOPLASMA OF MOST TISSUE, BUT THE LIVER, INTESTINE,
ADRENAL CORTEX AND STEROIDOGENIC REPRODUCTIVE
TISSUES ARE THE MOST ACTIVE.
* ACETYL-CoA IS THE INITIAL PRECURSOR.
* THE REGULATERY ENZYME IS HMG-CoA REDUCTASE.
LIPOPROTEIN: PROCESSING AND TRANSPORT OF FAT IN
THE BLOOD STREAM.
* DIETARY FAT  CHYLOMICRON, SYNTHISIZED BY
ENTEROCYTE.
-APOLIPOPROTEIN:APO B-48, Apo-A1, Apo CII, E
* VLDL IS SYNTHISIZED BY THE LIVER (ENDOGENOUS TG
AND CHOLESTEROL).
- APOLIPPROTEIN: APO B-100, Apo CII, Apo E.
* LDL: THE SOURCE VLDL, CONTAIN MOSTLY CHOLESTEROL.
- APOLIPOPROTEIN: APO B-100; RECEPTOR-MEDIATED
ENDOCYTOSIS.
* HDL: CHOLESTEROL COLLECTION, USING LCAT (LECITHIN-
COLESTEROL ACYL TRANSFERASE), TRANSPORT OF EXCESS
CHOLESTEROL, SCAVENGED FROM CELL MEMBRANE BACK
TO THE LIVER.
-APOLIPOPROTEIN: APO A1, CII, E.
ENZYME TO DEGRADE TG IN CHYLOMICRON AND VLDL:
LIPOPROTEIN LIPASE (PRESENT ON THE VASCULAR
ENDOTHELIUM OF ADIPOSE AND MUSCLE (APO CII AS
COFACTOR, LPL ACTIVITY INCREASES WHEN INSULIN
LEVELS RISE).