In 1929, Macheboeuf demonstrated that serum lipids do not ' circulate freely, but are bound to proteins in the form of large molecular complexes. Further investigations showed that these lipoproteins are composed of varying proportions of triglycerides, cholesterol, and phospholipids, bound to .a protein. By means of analytic ultracentrifugation, it is possible to separate different types of lipoproteins since these molecules have different density, and thus migrate at varying measureable rates under a great centrifugal force. With this technique it is possible to separate the serum lipoproteins into four major group; (a) chylomicra, (b) very low density lipoproteins, (c) low density lipo- proteins, and (d) alpha lipoproteins l. It is also known that serum lipoproteins differ sufficiently, not only in density but also in electrostatic charges, to permit their separation by electrophoretic techniques. Fredrickson, Levy, and LeeG, utilizing paper electrophoresis with barbital buffer, pH 8.6 containing 1 per cent albumin3, were able to separate four distinct lipoprotein fractions, which were labelled as: chylomicra, beta, pre-beta, and alpha lipoproteins. These fractions correlate well with those separated by the ultracentrifuge. These lipoproteins have been isolated, and their lipid composition determined4. Based on the patterns of serum lipoproteins and serum lipid levels, Frederickson et a/.2 have been able to propose a new classification for familial hyperlipo- proteinemias. The determination of serum lipoprotein patterns is not only a diagnostic tool, but it may also give significant information as to the patho- physiologic mechani,sm of a particular lipid metabolic derangement. The in- crease in chylomicra is usually associated with hyperlipidemias of exogenous origin; the pre-beta lipoproteins are synthesized in the liver from free fatty acids, triglycerides, and carbohydrates, and are the expression of an endo- genous hyperlipidemia; beta lipoproteins are related to cholesterol metabolism, either of endogenous or exogenous origin. PLASMA LIPOPROTEINS Plasma trrglycerrdes. cholesterol. and phospholrprds do not crrculate free, but they are bound to proterns to form complexes of hrgh molecular werght known as kpo. proteins. By means of electrophoresis or analytical ultra. centrifugation, lipoproteins can be separated Into four major groups. CHYLOMICRA PRE-BETA , BETA I ALPHA I i I p I i I 5 VERY LOW DENSITY ,-i LOW DENSITY LHIGH DENSITY 10' 400 20 0 z E Sf 2 DENSITY a ,1.006-p1.063-bl.21 0 TRIGLYCERIDES 0 CHOLESTEROL m PHOSPHOLIPIDS M PROTEINS MECHANISMS OF HYPERLIPIDEMIAS EXOGENOUS HYPERLIPIDEMIA CHYLOMICRA LIPOPROTEIN HEPARIN LIPASE 1 FAlTY ACIDS , + GLYCEROL H HYPERTRIGLYCERIDEMIAS YPERCHOLESTEROLEMIAS = ENDOGENOUS HYPERLIPIDEMIA TRIGLYCERIDES FREE FATTY ACIDS CARBOHYDRATES PRE.BETA u TRIGLYCERIDES 0 CHOLESTEROL m PHOSPHOLIPIDS PROTEINS CLASSIFICATION OF HYPERLIPO PROTEIN EMIAS Normal TYPE I EXOGENOUS HYPERLIPIDEMIA TYPE II HYPERCHOLESTEROLEMIA TYPE III BROAD BETA TYPE IV ENDOGENOUS HYPERLIPIDEMIA TYPE V MIXED HYPERLIPIDEMIA Electrophoresis of a normal fasting plasma reveals the following lipoproteins: Beta @U 85%), `Alpha (rv 15%). and small amounts of Pre-Beta. Chylomicra are absent. FASl-l NG PLASMA ABNOWALB TYPE I SYNONYMS BURGER-GRUTZ DISEASE GENETICS AUTOSOMAL RECESSIVE. RARE XANTHOMAS ONSET CHILDHOOD. HEPATOSPLENOMEGALY, CLINICAL ABDOMINAL PAIN, (PANCREATITIS?), MANIFESTATIONS LIPEMIA RETINALIS. CARDIOVASCULAR DISEASE: LOW PLASMA LIPIDS CHO: NORMAL OR SLIGHTLY INCREASED ._.- TRI: MARKEDLY INCREASED .--. -~- --- -- - --- GLUCOSE TOLERANCE NORMAL LIPOPROTEIN ELECTROPHORESIS MECHANISM EXOGENOUS HYPERLIPIDEMIA. DECREASED ACTIVITY OF LIPOPROTEIN LIPASE , TREATMENT (A) SYSTEMIC LUPUS ERYTHEMATOSUS (8) LYMPHOMA SECONDARY FORMS TYPE II TYPE 111 ESSENTIAL FAMILIAL HYPERCHOLESTEROLEMIA IDIOPATHIC klYPERLIPIDEMIA SIMPLE MENDELIAN DOMINANT. COMMON RECESSIVE (?I. LESS COMMON THAN II OR IV ONSET CHILDHOOD OR ADULTHOOD, ONSET ADULTHOOD. ARCUS CORNEA, HIGH INClDEzlCE OF ACCELERATED ATHEROSCLEROSIS CARDIOVASCULAR DISEASE CHO: MARKEDLY INCREASED CHO: INCREASED _ _ TRI: NORMAL OR SLIGHTLY INCREASED TRI: INCREASED USUALLY NORMAL ABNORMAL UNKNOWN. UNKNOWN. BETA LIPOPROTEINS WITH DERANGEMENT IN CHOLESTEROL INCREASED CONTENT IN TRIGLYCERIDES. METABOLISM CARBOHYDRATE INDUCED CLOFIBRATE. ESTROGENS, D-THYROXINE. NICOTINIC ACID CHOLESTYRAMINE. DIET: REDUCE CHOLESTEROL INTAKE. POLYUNSATURATED FATS CLOFIBRATE AND LOW CARBOHYDRATE DIET. WEIGHT CONTROL (1) LIVER DISEASE (2) NEPHROTIC SYNDROME (3) HYPOTHYROIDISM (4) hiY E LOiilA (5) hlACROGLOBULlNEMIA TYPE IV TYPE V IDIOPATHIC HYPERLIPIDEMIA DISEASE? SYNDROME? SIMPLE MENDELIAN PROBABLY GENETIC DOMINANT (?). MOST COMMON VARIANT OF TYPE IV (1). RARE ONSET ADULTHOOD, OBESITY ONSET EARLY ADULTHOOD, FREQUENT, ABDOMINAL PAIN HEPATOSPLENOMEGALY, OBESITY, (PANCREATITIS?), CARDIOVASCULAR ABDOMINAL PAIN, LIPEMIA RETINALIS, DISEASE. CARDIOVASCULAR DISEASE NOT FREQUENT CHO: NORMAL OR SLIGHTLY INCREASED CHO: NORMAL OR SLIGHTLY INCREASED ABNORMAL I ABNORMAL EXOGENOUS AND ENDOGENOUS ENDOGENOUS HYPERLIPIDEMIA, HYPERLIPIDEMIA (MIXED FORM) MAY BE CARBOHYDRATE INDUCED LIPOPROTEIN LIPASE ACTIVITY MA;Y BE LOW I WEIGHT CONTROL, RESTRICTION OF WEiGHT CONTROL, DIET LOW IN CARBOHYDRATES, CLOFIBRATE, FAi AND CARBOHYDRATES, CLOFIBRATE, NICOTINIC ACID PRbGESTATlONAL HORMONES (1) (2) (3) (4) (5) (6) (7) 3) (9) DIABETES MELLITUS I DIABETES MELLITUS PANCREATITIS GLYCOGEN STORAGE DISEASE INSULIN [)EPENDENT, NEPHROTIC SYNDROME PANCREATITIS PREGNANCY, GESTATIONAL HORMONES MYELOMA I ALCOHOLISM HYPOTHYROIDISM PROGERIA TOTAL LIPOATROPHY References: 1. Lindgren, F. T., Elliot, H. A., and Gofman, J. W.: The ultracentrifugal charac- terization and isolation of human blood lipids and lipoproteins with applica- tions to the study of atherosclerosis, J. Physiol. Chem. 55:80 1951. 2. Fredrickson, D. S., Levy, R. I., and Lees, R. S.: Fat transport in lipoproteins - an integrated approach to mechanisms and disorders, New Eng. J. Med. 276:32-44 (Jan. 5), 94-103 (Jan. 12), 148-156 (Jan. 19), 215-226 (Jan. 26), 273-281 (Feb. 2), 1967. 3. Lees, R. S., and Hatch, F. T.: Sharper separation of lipoprotein species by paper electrophoresis in albumin-containing buffer, J. Lab. Clin. Med. 61: 518 1963. 4. Bragdon, J. H., Havel, R. J., and Boyle, E.: Human serum lipoproteins. I. Chemical composition of four fractions, J. Lab. Clin. Med. 42:48 1956. 5. Fleischmajer, R.: The Dyslipidcses, Springfield, III., Charles C. Thomas, 1960. 6. Fleischmajer, R.: Familial hyperlipoproteinemia Type III. Arch. Dermat., 100: 401. 1969. LIFT HERE