II. Definitions

  1. Lipids
    1. Organic molecules containing Hydrocarbons
    2. Poorly soluble in water, but soluble in organic solvents
    3. Examples include free Fatty Acids, Triglycerides, phospholipids
  2. Cholesterol
    1. Lipid precursor for steroid Hormones, bile acids and Vitamin D
  3. Triglyceride
    1. Lipid composed of three molecules of Fatty Acid esterified to glycerol
    2. Triglycerides are a non-polar fat synthesized from Carbohydrates or ingested
    3. Triglycerides are High Energy Molecules that are stored for later use in animal adipose cells (fat cells)
  4. Lipoprotein
    1. Serum Proteins that solubilize hydrophobic lipids (Triglycerides, Cholesterol esters), key to lipid transport through the blood stream
    2. Contain two components: Spherical hydrophobic core (Cholesterol, Triglycerides) and hydrophilic shell (phospholipids, apolipoproteins)
    3. Classified by density (Chylomicrons, VLDL, LDL, HDL) which transport Cholesterol and Triglycerides to and from the liver and other tissues
      1. Chylomicrons and VLDL transport both Triglycerides and Cholesterol esters
      2. Low Density Lipoproteins (LDL) primarily transports Cholesterol
      3. High Density Lipoproteins (HDL) is a Cholesterol scavenger returns excess Cholesterol and LDL remnants back to the liver
  5. Sphingolipid
    1. Similar to Triglycerides (but with a serine backbone and other slight structural changes)
    2. Includes sphingosine and ceramides, of which sphingomyelin is a key component of myelin nerve sheath

III. Physiology: Lipid Metabolism

  1. fatMetabolism.png
  2. See Fat Metabolism
  3. Fats are a high energy (9 kcals/g), long term energy source
  4. Intestinal Digestion and Absorption of fats
    1. Duodenal bile salts emulsify fats into small droplets
    2. Enzymatic breakdown by intestinal and pancreatic agents
      1. Lipase (intestinal, pancreatic) lyse Triglycerides to monoglycerides and free Fatty Acids
      2. Esterases lyse Cholesterol to free Cholesterol and free Fatty Acids
      3. Phospholipases lyse phospholipids to free Fatty Acids and lysophospholipids
    3. Small micelles form from fat breakdown products and bile acids
    4. Micelles carry fats to intestinal epithelial cell brush border for absorption
      1. Bile salts allow for absorption of polar lipids
    5. Bile salts are reclaimed by enterohepatic circulation
      1. Bile salts absorbed in ileum are transported back to liver via portal circulation
  5. Intestinal Epithelial cell Processing of Fats
    1. Re-forming of lipids
      1. Triglycerides re-form from free Fatty Acids and monoglycerides
      2. Cholesterol esters re-form from free Fatty Acids and Cholesterol
      3. Phospholipids re-form from free Fatty Acids and lysophospholipids
    2. Chylomicrons
      1. Form from Apoproteins combined with Triglycerides, Cholesterol to phospholipids
      2. Chylomicrons move from intestinal epithelial cells into Lymphatic System
      3. Triglycerides are carried by Chylomicrons to Muscle and fat cells
        1. Triglycerides are lysed into free Fatty Acids by capillary Lipoprotein Lipase
        2. Free Fatty Acids are then absorbed by Muscle and fat cells
        3. Triglycerides reform from free Fatty Acids within Muscle and fat cells (esterification)
    3. Other Lipoproteins (VLDL, LDL, HDL)
      1. Form from Cholesterol processing in the liver

IV. Physiology: Lipid Functions

  1. Energy Source
    1. Fatty Acids are stored for later energy use, bound to glycerol, as Triglycerides within fat cells
      1. Fatty Acids are synthesized by adding, in repeated cycles, 2 carbon atoms (acetyl CoA)
      2. Fatty Acid synthesis occurs in the cytoplasm of most cells to supply numerous uses including cell wall
    2. Fatty Acids are burned as fuel in the Kreb Cycle (TCA Cycle)
      1. Fatty Acids are degraded (oxidized) by removing, in repeated cycles, 2 carbon atoms (acetyl CoA)
      2. Energy from each extracted acetyl coA enters the Kreb Cycle
      3. Each Kreb Cycle generates NADH and FADH2 (total energy 17 ATP)
    3. Fats offer high energy stores (9 KCals/g) compared with Carbohydrates and Proteins (4 kcals/g)
      1. Triglycerides are non-polar and bind less water (more compact than Carbohydrates, Proteins)
      2. Each triglcyeride contains 3 Fatty Acids, each with 16 to 18 carbons (fueling 24-27 Kreb Cycles)
  2. Cell Membrane Components
    1. Cholesterol, Glycolipids and phospholipids are important components of cell membranes
  3. Cholesterol Derivatives
    1. AdrenalFunction.png
    2. CholesterolDerivedSteroidHormones.png
    3. Cholesterol
      1. Cholesterol is a sterol ring structure (four interlinked aromatic rings) critical in physiology
      2. Cholesterol may either be ingested or synthesized
      3. Cholesterol synthesis (primarily in the liver)
        1. Acetyl CoA is converted to isoprene (5 carbon structure)
        2. Isoprene is combined with other isoprene molecules to form 10, 15 and 30 carbon rings
        3. Cholesterol (27 carbons) is among many Isoprenoids (isoprene derived molecules)
          1. Others Isoprenoids include all fat soluble Vitamins (A, D, E and K) and Coenzyme Q
    4. Steroid Hormones are derived from Cholesterol with unique side chains at the C17 carbon
      1. Pregnenolone (21 carbons) is derived from Cholesterol
        1. Sex Hormones, mineralcorticoids and Glucocorticoids are all formed from Pregnenolone
      2. Sex Hormones
        1. Testosterone (primarily synthesized in the Testes)
        2. Estrogen and Progesterone (primarily synthesized in the ovary)
        3. Dehydroepiandrosterone and Androstenedione (androgens synthesized in the Adrenal Cortex)
      3. Mineralcorticoids (e.g. Aldosterone, synthesized in the Adrenal Cortex)
      4. Glucocorticoids (e.g. Cortisol, synthesized in the Adrenal Cortex)
    5. Other Cholesterol derivatives and related Isoprenoids
      1. Bile Acids (derived from Cholesterol)
      2. Fat Soluble Vitamins (Vitamin A, Vitamin D, Vitamin E, Vitamin K)
      3. Coenzyme Q
  4. Fatty Acid Derivatives (esp. Arachidonic Acid Derivatives)
    1. FattyAcidDerivatives.png
    2. General
      1. Basic structure is a 5 carbon ring "head" with two 6 to 9 carbon chain "legs"
      2. Functions vary by specific molecule, but function in general is summarized here
    3. Thromboxanes
      1. Increase Platelet aggregation
    4. Leukotrienes
      1. Leukocyte chemotaxis
    5. Prostacyclin
      1. Inhibits Platelet aggregation
      2. Vasodilates
    6. Prostaglandins
      1. Contracts Smooth Muscle (e.g. Vasoconstriction, bronchoconstriction, uterine contraction)
      2. Increases inflammatory response as well as pain and fever
  5. Lipoproteins
    1. Serum Proteins that solubilize hydrophobic lipids (Triglycerides, Cholesterol esters)
      1. Key to lipid transport through the blood stream
      2. Altered Lipoprotein metabolism may result in Hyperlipidemia and increased cardiovascular risk
    2. Contain two components
      1. Spherical hydrophobic core of Cholesterol ester or Triglycerides
      2. Hydrophilic shell of phospholipids, Cholesterol and apolipoproteins
    3. Classified by density
      1. Chylomicrons
        1. Lipoproteins carrying Triglycerides and Cholesterol esters from the Small Intestine via Lymphatics to central circulation
        2. Transport Triglycerides to the fat cells and Muscle, and remaining Cholesterol to the liver
      2. Very Low Density Lipoproteins (VLDL)
        1. Similar to Chylomicrons (which have the same density), carrying both Triglycerides and Cholesterol esters
        2. Very light (0.93 to 1.006 g/ml), large (30-80 nm) Lipoproteins whose cores are primarily Triglycerides
        3. Surface is a phospholipid and Cholesterol monolayer with embedded apolipoprotein B, E and C
        4. Transport Triglycerides from the liver to Muscle and fat cells
          1. As Triglycerides and Apo C are off-loaded, VLDL becomes intermediate density Lipoprotein (IDL), and then LDL Cholesterol
      3. Low Density Lipoproteins (LDL)
        1. Cholesterol laden particles for transport from liver, throughout the body (see Cholesterol function above)
        2. Small (18-25 nm) and light (1.019 to 1.063 g/ml) Lipoproteins
        3. Primarily contain a core of Cholesterol esters and a lower concentration of Triglycerides
        4. LDL transports Cholesterol esters from the liver throughout the body
        5. Phospholipid monolayer surface contains a single Apolipoprotein A100
      4. High Density Lipoproteins (HDL)
        1. HDL is synthesized in the liver as empty, non-lipid bound Proteins (apolipoprotein A1)
          1. Start as the smallest (4-13 nm) and most dense (>1.063 g/ml) Lipoproteins, without a Cholesterol core
        2. HDL is a Cholesterol scavenger returns excess Cholesterol and LDL remnants back to the liver, for bile synthesis
        3. HDL also transports apolipoproteins C2 and E to and from Triglyceride rich Lipoproteins
        4. Lecithin-Cholesterol acyl transferase (LCAT) enzyme is bound to HDL
          1. LCAT converts free Cholesterol into more hydrophobic Cholesterol esters, which are sequestered into Lipoproteins
  6. Sphingolipids
    1. sphingolipids.png
    2. Similar to Triglycerides with 2 exceptions
      1. Serine backbone (with a NH2 at the middle carbon) instead of a glycerol backbone
      2. First carbon group is a COOH instead of CH2-OH
    3. Sphingosine
      1. Analogous to a monoglyceride, with the first serine carbon attached to a Fatty Acid (palmitoyl CoA)
    4. Ceramide
      1. Analogous to a diglyceride, with the first 2 serine carbon chains attached to Fatty Acids
      2. Ceramide serves as a base for many molecules with different attachments at the third carbon
        1. Sphingomyelin (choline at the third carbon), a key component of the Myelin Sheath of nerves
        2. Glycolipids (sugar-lipid combinations)
          1. Cerebroside (Glucose or Galactose at the third carbon)
            1. Sulfatides contain Galactose with an attached sulfate
          2. Ganglioside (Oligosaccharide, with multiple linked sugars at the third carbon)
            1. Also contain sialic acid (N-acetyl neuraminic acid, NANA), an 11-carbon amino-sugar
          3. Globoside
            1. Similar to Gangliosides, but without sialic acid

V. Precautions

  1. Total Cholesterol <175 mg/dl in elderly: Increased mortality
    1. Schupf (2005) J Am Geriatr Soc 53:219-26 [PubMed]

VII. Patient Education

  1. Mnemonic: Lower L-DL, Higher H-DL

VIII. References

  1. Goldberg (2001) Clinical Biochemistry, Medmasters, Miami, p. 17-23
  2. Guyton and Hall (2006) Medical Physiology, 7th Ed, Elsevier Saunders, Philadelphia, p. 829-58

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Related Studies

Ontology: Cholesterol (C0008377)

Definition (MEDLINEPLUS)

Cholesterol is a waxy, fat-like substance that occurs naturally in all parts of the body. Your body needs some cholesterol to work properly. But if you have too much in your blood, it can combine with other substances in the blood and stick to the walls of your arteries. This is called plaque. Plaque can narrow your arteries or even block them.

High levels of cholesterol in the blood can increase your risk of heart disease. Your cholesterol levels tend to rise as you get older. There are usually no signs or symptoms that you have high blood cholesterol, but it can be detected with a blood test. You are likely to have high cholesterol if members of your family have it, if you are overweight or if you eat a lot of fatty foods.

You can lower your cholesterol by exercising more and eating more fruits and vegetables. You also may need to take medicine to lower your cholesterol.

NIH: National Heart, Lung, and Blood Institute

Definition (NCI) An animal sterol found in the body tissues (and blood plasma) of vertebrates. It can be found in large concentrations within the liver, spinal cord, and brain. Cholesterol is an important component of the membranes of cells, providing stability. It is the major precursor for the synthesis of vitamin D, of the various steroid hormones, including cortisol, cortisone, and aldosterone in the adrenal glands, and of the sex hormones progesterone, estrogen, and testosterone. Cholesterol also has an important role for the brain synapses as well as in the immune system. In conditions featuring elevated low density lipoproteins (LDL), cholesterol often forms plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease.
Definition (NCI_NCI-GLOSS) A waxy, fat-like substance made in the liver, and found in the blood and in all cells of the body. Cholesterol is important for good health and is needed for making cell walls, tissues, hormones, vitamin D, and bile acid. Cholesterol also comes from eating foods taken from animals such as egg yolks, meat, and whole-milk dairy products. Too much cholesterol in the blood may build up in blood vessel walls, block blood flow to tissues and organs, and increase the risk of developing heart disease and stroke.
Definition (NCI_CRCH) Lipid composed of 27 carbon atoms which form three fused cycloheane (6-carbon) rings, a cyclopentane (5-carbon ring) and a side chain of 8 carbon atoms. (Ensminger et al).
Definition (MSH) The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Definition (CSP) C27H46O, the major fatty steroid alcohol of vertebrate animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Concepts Biologically Active Substance (T123) , Steroid (T110)
MSH D002784
SnomedCT 84698008
LNC LP15493-7, LP100019-1, MTHU003147
English Cholesterol, Cholest-5-en-3-ol (3beta)-, (3beta)-Cholest-5-en-3-ol, Cholesterol [Chemical/Ingredient], cholesterol, CHOLESTEROL, 5-cholesten-3B-ol, (-)-Cholesterol, Cholesterol (substance)
Swedish Kolesterol
Czech cholesterol
Finnish Kolesteroli
Japanese コレステリン, コレステロール
Polish Cholesterol
Spanish colesterol (sustancia), colesterol, Colesterol
French Cholestérol
German Cholesterol
Italian Colesterolo
Portuguese Colesterol

Ontology: Chylomicrons (C0008731)

Definition (CSP) class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues.
Definition (MSH) A class of lipoproteins that carry dietary CHOLESTEROL and TRIGLYCERIDES from the SMALL INTESTINE to the tissues. Their density (0.93-1.006 g/ml) is the same as that of VERY-LOW-DENSITY LIPOPROTEINS.
Concepts Biologically Active Substance (T123) , Lipid (T119) , Amino Acid, Peptide, or Protein (T116)
MSH D002914
SnomedCT 41458000, 17534000
LNC LP15502-5, MTHU004922
English Chylomicrons, chylomicron, Chylomicron, Chylomicrons [Chemical/Ingredient], chylomicrons, Extracellular lipid droplet, Extracellular lipid droplet (substance), Chylomicron (electron microscopy), Floating beta-lipoprotein, Chylomicrons (substance)
Swedish Kylomikroner
Czech chylomikrony
Finnish Kylomikronit
Polish Chylomikrony
Spanish quilomicrón (microscopia electrónica), gotita de lípido extracelular (sustancia), gotita de lípido extracelular, quilomicrones (sustancia), quilomicrones, Quilomicrones
French Chylomicron
German Chylomikronen
Italian Chilomicroni
Portuguese Quilomícrons

Ontology: Glycolipids (C0017950)

Definition (MSH) Any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol (see GLYCERIDES), a sphingoid, a ceramide (CERAMIDES) (N-acylsphingoid) or a prenyl phosphate. (From IUPAC's webpage)
Definition (CSP) compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol, a sphingoid, a ceramide, or a prenyl phosphate.
Concepts Biologically Active Substance (T123) , Lipid (T119)
MSH D006017
SnomedCT 19238008
English Glycolipids, Glycolipids [Chemical/Ingredient], glycolipids, glycolipid, Glycolipids, NOS, Glycolipid, Glycolipids (substance), Glycolipid (substance)
Spanish glucolípidos, glucolípido (sustancia), glucolípido, glucolípidos (sustancia), Glucolípidos
Swedish Glykolipider
Czech glykolipidy
Finnish Glykolipidit
Polish Glikolipidy
French Glucolipides, Glycolipides
German Glycolipide, Glykolipide
Italian Glicolipidi
Portuguese Glicolipídeos

Ontology: Hyperlipidemia (C0020473)

Definition (NCI) Elevated levels of lipids in the blood.
Definition (CSP) excess of lipids in the blood.
Definition (MSH) Conditions with excess LIPIDS in the blood.
Concepts Disease or Syndrome (T047)
MSH D006949
ICD10 E78.5
SnomedCT 154743001, 190782002, 154739000, 267499005, 55822004
English Hyperlipemia, Hyperlipemias, HYPERLIPAEMIA, Hyperlipidaemia NOS, Hyperlipidaemia, unspecified, Hyperlipidemia, unspecified, Hyperlipidemias, Hyperlipidemia NOS, hyperlipemia, hyperlipidemia (diagnosis), hyperlipidemia, Hyperlipaemia, Hyperlipidemias [Disease/Finding], lipidaemia, excessive fat in the blood, hyperlipidaemias, hyperlipidemias, lipidemia, Hyperlipidaemia NOS (disorder), Hyperlipidemia NOS (disorder), Disorder characterized by hyperlipidemia, Hyperlipidaemia, Lipidemia, HLD - Hyperlipidaemia, HLD - Hyperlipidemia, Hyperlipidemia (disorder), Lipidaemia, lipemia, lipoidemia, Hyperlipidemia, NOS, Hyperlipidaemia, NOS, Hyperlipidemia, hyperlipidaemia
Portuguese HIPERLIPEMIA, Hiperlipidemia NE, Hiperlipidemias, Hiperlipidemia, Hiperlipemia
Spanish HIPERLIPEMIA, Hiperlipidemia NEOM, Hiperlipidemias, hiperlipidemia, SAI (trastorno), hiperlipidemia, SAI, Hyperlipidaemia NOS, Hyperlipidemia NOS, hiperlipemia, hiperlipidemia (trastorno), hiperlipidemia, Hiperlipidemia, Hiperlipemia
Dutch hyperlipemie, hyperlipidemie NAO, Hyperlipidemie, niet gespecificeerd, hyperlipidemie
French Hyperlipidémie SAI, Hyperlipidémie, HYPERLIPEMIE, Hyperlipémies, Hyperlipidémies, Hyperlipémie
German Hyperlipaemie, Hyperlipidaemie NNB, HYPERLIPAEMIE, Hyperlipidaemie, nicht naeher bezeichnet, Hyperlipidaemie, Hyperlipämie, Hyperlipidämie
Italian Iperlipidemia NAS, Condizione iperlipidemica, Lipidi elevati, Valori lipidici elevati, Iperlipidemia, Iperlipemia
Japanese 高脂血症NOS, コウシケッショウNOS, コウシケッショウ, コウシケツショウNOS, コウシケツショウ, 高脂質血, 高脂血症, 脂血症, 脂肪過剰血, 脂質過剰血症, 脂肪血症, 高脂肪血症, リポイド過多血症, 高脂血症(コウシケツショウ), 脂質異常症, 高脂質血症
Swedish Hyperlipemier
Czech hyperlipémie, hyperlipidémie, Hyperlipidemie NOS, Hyperlipemie, Hyperlipidemie
Finnish Hyperlipidemiat
Korean 상세불명의 고지혈증
Polish Hiperlipidemia samoistna rodzinna, Hiperlipidemie
Hungarian Hyperlipidaemia, Hyperlipaemia, Hyperlipidaemia k.m.n.
Norwegian Høyt blodfett, Hyperlipidemier, Hyperlipemi, Hyperlipidemi

Ontology: Lipoproteins (C0023820)

Definition (MSH) Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.
Definition (NCI) An important class of serum proteins in which a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol and apolipoproteins. Classified according to density: chylomicrons, large low density particles, very low density, low density and high density species. Important in lipid transport, especially cholesterol transport in the blood stream. Abnormalities in lipoprotein metabolism have been implicated in certain heart diseases.(On-line Medical Dictionary)
Concepts Amino Acid, Peptide, or Protein (T116) , Biologically Active Substance (T123)
MSH D008074
SnomedCT 19237003, 301861005
LNC LP15711-2, MTHU007260
English Lipoprotein, Circulating Lipoproteins, Lipoproteins, Circulating, Lipoproteins [Chemical/Ingredient], lipoproteins, lipoprotein, Lipoprotein (substance), Lipoprotein, NOS, Lipoprotein (substance) [Ambiguous], Lipoproteins
French LPP (Lipoprotéine), Lipoprotéine, Lipoprotéines circulantes, Lipoprotéines
Swedish Lipoproteiner
Czech lipoproteiny
Finnish Lipoproteiinit
Italian Lipoproteina, Lipoproteine circolanti, Lipoproteine
Polish Lipoproteiny, Lipoproteidy
Japanese 脂蛋白質, リポ蛋白質, リポタンパク質, リポ蛋白
Spanish lipoproteína (concepto no activo), lipoproteína (sustancia), lipoproteína, Lipoproteínas
German Lipoproteine
Portuguese Lipoproteínas

Ontology: Sphingolipids (C0037900)

Definition (NCI_CRCH) A class of dietary lipids containing a long-chained sphingosine group (unsaturated amino alcohol with formula C18H37NO2), fatty acids bound to the NH2 group as an amide, and either sugars or phosphoric acid and alcohols bound to the primary hydroxy group .
Definition (NCI) Any lipid derived from the aliphatic amino alcohol sphingosine, in which a single fatty acid is covalently bound to sphingosine via an amide linkage. Various ester-linked substituents can result in generation of ceramides, sphingomyelins and glycosphingolipids.
Definition (MSH) A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)
Definition (CSP) family of ceramides with various hydrophilic, O-linked head groups; found in membranes, especially in neural tissue.
Concepts Lipid (T119)
MSH D013107
SnomedCT 47407008
English Sphingolipids, sphingolipid, Sphingolipids [Chemical/Ingredient], sphingolipids, Sphingolipid, Sphingolipid (substance), Sphingolipid, NOS
Swedish Sfingolipider
Czech sfingolipidy
Finnish Sfingolipidit
Croatian Not Translated[Sphingolipids]
Polish Sfingolipidy
Portuguese Lisosfingolipídeos, Esfingolipídeos
Spanish esfingolípido (sustancia), esfingolípido, Esfingolípidos
French Sphingolipides
German Sphingolipide
Italian Sfingolipidi

Ontology: Cholesterol, serum or whole blood, total (C0373576)

Concepts Laboratory Procedure (T059)
CPT 82465
English ASSAY BLD/SERUM CHOLESTEROL, Assay bld/serum cholesterol, Cholesterol, serum or whole blood, total, CHOLESTEROL SERUM/WHOLE BLOOD TOTAL