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Lesson 6: Carbohydrates
Clinical Chemistry 1
BS Medical Technology BSMT 3-3 | Prof. Eric E. Carpo
CARBOHYDRATES
● are composed of C, H, O ● originally referred to as “hydrates of carbon” ● the empirical formula is C(H 2 O)n o glucose- C 6 H 12 O 6 o sucrose- C 12 H 22 O 11 ● hydrates of aldehyde or ketone derivatives based on the location of C=O (Carbonyl group) functional group CLASSIFICATION I. Based on number of carbon atoms a. 3C ● Trioses ● glyceraldehyde b. 4C ● Tetroses ● erythrose c. 5C ● Pentoses ● ribose d. 6C ● Hexoses ● glucose, fructose, galactose ● Biologically important to us e. 7C ● Heptoses ● sedoheptulose f. 9C ● Nonoses ● neuraminic acid II. Based on stereoisomers a. L-glucose b. D-glucose ● Our body absorbs only those in D-isomer, specifically the D-glucose. If L-glucose, enzymes are needed to convert it into D-glucose. ● All sugars can be absorbed if they are in the D-isomer III. Based on the number of sugar units a. Monosaccharides ● simple sugars ● cannot be hydrolyzed to a simpler form ● they contain 3, 4, 5 or 6 C atoms ● ex. glucose, fructose, galactose, ribose & deoxyribose ● this sugar unit can be only absorbed by the body. b. Disaccharides ● composed of 2 monosaccharides joined by a glycosidic linkage or bond ● on hydrolysis the disaccharides will split into 2 monosaccharides by enzymatic action which will then be absorbed ○ Sucrose ■ glucose + fructose ○ Lactose ■ glucose + galactose ■ Milk sugar ■ Lactose intolerant: lacks of lactase ○ Maltose ■ glucose + glucose ■ Seen in wheat c. Oligosaccharides ● 3 to 10 monosaccharides d. Polysaccharides
● composed of more than 10 monosaccharides ● Starch ○ storage form of sugar in plants ● Glycogen ○ storage form of sugar in humans ○ Important in human GLUCOSE METABOLISM
1. GLUCOSE ● is the primary source of energy for humans. ● The brain is completely dependent on glucose for energy; nervous tissue cannot concentrate or store CHO (carbo) therefore it is critical to maintain a steady supply of glucose to the tissue ● most ingested CHO are polymers like starch & glycogen which are broken down by salivary amylase & pancreatic amylase to dextrins & disaccharides, which are further hydrolyzed to monosaccharides by maltase (enzyme released by the intestinal mucosa. ● Sucrase & lactase hydrolyze sucrose to glucose = fructose & lactose to glucose + galactose respectively. ● upon conversion to monosaccharides, they are transported to the liver, which plays a major role in glucose regulation ● glucose metabolism generates pyruvic acid, lactic acid & acetyl-coenzyme A as intermediate products ● the complete oxidation of glucose yields CO2, water & ATP PATHWAYS IN GLUCOSE METABOLISM ● Embden-Meyerhof pathway ● Hexose monophosphate pathway ● Tricarboxylic pathway (Kreb Cycle) 2. STARCH ● is initially broken down by salivary amylase into dextrins & disaccharides ● then by pancreatic amylase. ● The disaccharides are broken down into monosaccharides by sucrase, lactase & maltase. **3. The glucose may be used as energy or stored in the liver as glycogen.
- Terminologies in glucose metabolism: a. Glycolysis** ● metabolism of glucose to pyruvate or lactate for energy. ● Lysis is breakdown so breakdown of glucose ○ Hyperglycemic ■ Increases blood sugar level ○ Hypoglycemic ■ Decreases blood sugar sugar level ● Glycolysis performs Hypoglycemic action since it breaks down the glucose. b. Glycogenesis ● conversion of glucose to glycogen ● It performs hypoglycemic action since glucose was stored in the liver in the form of glycogen. Therefore, the sugar in the blood is decreased. c. Glycogenolysis ● breakdown of glycogen to glucose for energy ● It performs hyperglycemic action since it produces glucose.
Insulin is rejected because it will only be broken down by the hydrochloric acid ● it has a 21-amino acid A chain & a 30-amino acid B chain linked by disulfide bonds ● it is initially synthesized as a longer single-polypeptide chain called Pre-proinsulin (11500 daltons), cleavage results to proinsulin ( daltons), the immediate precursor of insulin. Proinsulin has only 5% activity of insulin. (may Chains A, B & C, pero walang activity) ● Proinsulin is converted to insulin by the enzymatic removal of the 31-amino acid peptide ● Proinsulin is bigger and has A, B, and C but has nomactivity making it weak. The removal of the C-chain is called C peptide. ● The segment that connects the A & B chains known as C-peptide ● it is the only hypoglycemic agent ● it promotes glycogenesis, lipogenesis & glycolysis; it decreases glycogenolysis ● it enhances membrane permeability to cells in the liver, muscle & adipose tissue ● insulin assays may be falsely low in hemolyzed specimens ● Most important hormone in biochem ● It is the only hypoglycemic agent in hormone regulation ● It promotes glycogenesis, lipogenesis & glycolysis; it decreases glycogenolysis ● It enhances membrane permeability to cells in liver, muscle & adipose tissue. Glucose cannot directly enter the cell. Insulin will help by increasing the permeability and pull glucose inside ● Insulin assays must be falsely low in hemolyzed specimens ● If the pancreas fails, insulin is gone and there would be no other hormone to help with lowering the blood sugar level.
- Glucagon ● secreted by the alpha cells ● Counter regulatory or counterpart of insulin ● it stimulates glucose production; hyperglycemic agent ● it regulates hepatic glycogenolysis, gluconeogenesis & ketogenesis ● it is released during stress & fasting states ● Proglucagon is synthesized by the alpha cells of the Islets & L cells of the distal small bowel
- Somatostatin ● secreted by the delta cells of the Islets of Langerhans ● it inhibits insulin, glucagon, & growth hormone action ● it is also synthesized in the paraventricular & arcuate nuclei of the hypothalamus (neuroendocrine hormone)
- Thyroid hormones (T3 & T4) ● stimulates glycogenolysis & gluconeogenesis ● Hyperglycemic action
- Epinephrine ● fight or flight response ● secreted by the chromaffin cells of the adrenal medulla ● stimulates glycogenolysis & lipolysis ● inhibits insulin ● Hyperglycemic action
- Cortisol & corticosteroids ● produced by the adrenal cortex ● stimulates gluconeogenesis & lipolysis ● decreases intestinal entry of glucose into the cell ● Hyperglycemic action since it prevents the uptake of glucose in the cell making it stay in the blood circulation ● Like those who drink steroids
- Growth Hormone (GH) ● secreted by the anterior pituitary ● stimulates glycogenolysis & glycolysis ● insulin antagonist; hyperglycemic action ● Acromegaly or gigantism
● Tumor in the anterior pituitary leading to excessive production of the growth hormone ● Possibility of having diabetes as well because of the hyperglycemic action
- Adrenocorticotropic hormone (ACTH) ● secreted by the anterior pituitary ● stimulates glycogenolysis & gluconeogenesis ● insulin antagonist ● Therefore, insulin is the most important hormone because it is the **one and only hypoglycemic agent CLINICAL SIGNIFICANCE & DISEASE STATES IN GLUCOSE METABOLISM
- Hyperglycemia** ● increase blood glucose concentration DIABETES MELLITUS (DM) ● metabolic disease characterized by hyperglycemia due to insufficient insulin levels, insulin resistance or both. ● is a group of diseases in which blood glucose levels are elevated because of deficient insulin secretion & or abnormal insulin action ● fasting plasma glucose greater than or equal to 126 mg/dL on more than 1 testing are diagnostic ● the primary symptoms are o hyperglycemia o glucosuria o 3Ps: polyuria, polydipsia, polyphagia ▪ Polyuria: constant urine ▪ Polydipsia: constant drinking ▪ Polyphagia: constant eating o sudden weight loss & during acute episodes of DM, ketonemia & ketonuria Explanation of the 3Ps ● In the case of hyperglycemia, there is increased blood sugar level in the circulation. ● Scenario: Too much sugar in your coffee so the remedy is to add more water ● Glucose is a highly osmotic substance! There is little to no water in the intravascular space because of the increased blood sugar level. ● It will draw out the water from the intracellular space since our cells have water. The principle is that water will go to where there is less! So water from the intracellular space will go to the intravascular space. ● Meaning cells → circulation ● It will result to an increase in fluid volume in your veins or circulation = polyuria (increased urine output) ● Since the cells are dehydrated, you will tend to drink more water = polydipsia ● The cycle goes on and on ● Even with high blood sugar level, a person will still feel hungry because glucose cannot enter the cells due to the lack of insulin. Remember that insulin is for the glucose uptake. Therefore, the cell is starved, and no ATP is produced. There is a feeling of weakness which makes the person want to eat = polyphagia ● They say that diabetes is starvation in the face of plenty. COMPLICATIONS OF DM INCLUDES: A. ESRD ● end stage of renal disease ● Sakit sa bato B. Non-Traumatic Amputation ● Amputation not because of an accident but due to problems in circulation ● BTK - below the knee amputation ● AAK - above the knee amputation C. New Blindness ● in adults aging 20-74 y/o ● Cataracts ● Retinopathy ○ Rupture of small veins in the eyes ● Diabetic retinopathy ○ Excessive pumping of blood due to glucose blockage
● Characterized by insulin insufficiency or Hyperglycemia ○ There is minimal insulin deficiency ○ There is presence of insulin but cannot enter the cell unlike in Type 1 with no insulin at all. ● Risk factors ○ Obesity ○ sedentary lifestyle ○ family history ○ advanced age ○ Ethnicity ○ history of gestational DM ○ Impaired glucose metabolism, hypertension & dyslipidemia. ● Ketosis is rare, instead more prone to
● Mechanisms involved in the development of type 2 DM : ○ as a compensatory mechanism for glucose tolerance the pancreas has to secrete insulin ○ hyperglycemia is also toxic to the β cells of the pancreas disrupting function & impairing insulin secretion ● In Type 2 DM, there is insulin but it is resistant making it hard to enter the target cell due to the large number of fats. Glucose cannot enter because the fat covered insulin’s receptor for the target cell. ● Another reason related to the pancreas. When you eat, insulin increases to lower the blood sugar. When you keep on eating, the production of insulin is also nonstop thus increasing its level in your blood. After how many years, your pancreas will fail (pancreatic exhaustion) and insulin production will be minimal. This occurs during mid 30s – 40s. ● Also, when the level of insulin is always high, it will be toxic and destroy the receptors in your cell. Nothing will be left once you grow old. This is called hyperinsulinism. ● Type 2 DM has milder symptoms compared to Type
● When left untreated, it will result to nonketotic hyperosmolar coma. ● It is the overproduction of glucose (>500 mg/dL) ● Severe dehydration, electrolyte imbalance, incomplete BUN and creatinine ● Genes are probabilistic and not deterministic. Probabilistic = there’s a chance that you’ll have diabetes, but you can avoid it ● Deterministic = 100% chance that you’ll have diabetes Central or Truncal Obesity Hyperglycemia ● Laboratory Findings ○ ↑ glucose in plasma and urine
○ ↑ urine specific gravity ○ ↑ serum and urine osmolality ○ Ketones in serum and urine (ketonemia and ketonuria) → acetoacetate, B-hydroxybutyrate & acetoin is produced from FA ○ (arrow down) blood and urine pH (acidosis) ○ Electrolyte imbalance ○ → (arrow down) Na - polyuria and shift of water from cells, ○ → ↑ K - displacement from cells in acidosis C. Gestational DM ● impaired inability to metabolize glucose during pregnancy due to insulin deficiency, metabolic or hormonal changes ● screening is a common practice between 24-28 weeks of gestation ● glucose intolerance with onset during pregnancy (screening is done at 28 wks) ● due to metabolic & hormonal changes ● Increased risk or associated with perinatal complications ● GDM (uncontrolled, di naggagamot) converts to DM within 10 yrs in 30-40% cases ● increased risk of developing type 2 DM (30-40% within 10 yrs) ● Infants are at increased risk for respiratory syndrome, hypocalcemia & hyperbilirubinemia ● Progesterone is the hormone for the thickening of the uterus during pregnancy. Levels of lactose (for milk) and blood sugar increases. ● Cortisol also increases. ● The mother eats a bigger portion and can have an increased blood sugar level which can affect the baby. Blood pressure can also increase. D. Secondary DM ● caused by other conditions & diseases ● pancreatic diseases ○ acromegaly (GH excess) ○ Cushing’s dse (excess cortisol) ○ pheochromocytoma (excess catecholamines) ○ glucagonoma (excessive glucagon) ○ somatostatinoma (escessive production of somatostatin) ○ primary aldosteronism ○ severe liver disease ○ administration of certain drugs, hormones & chemicals ● Maturity Onset-type Diabetes of the Young (MODY) ○ occurs in younger individuals who have impaired pancreatic β cells & still can produce insulin but demonstrate insulin resistance. ● Genetic Disorders ○ Down’s syndrome ○ Klinefelter’s ○ Rabson-Mendengall syndrome ○ Huntington’s chorea ○ Turner’s syndrome ● Drugs that interfere with insulin release from β cells ○ cyclosporine ○ thiazides ○ phenytoin ● Inducing insulin resistance ○ glucocorticoids ○ oral contraceptives LABORATORY FINDINGS IN HYPERGLYCEMIA
- Increase glucose in plasma & urine
- increase in urine specific gravity
- Increase serum and urine osmolarity (dissolved substances) ● ketones in serum and urine (ketonemia and ketonuria)
- Decrease blood and urine pH (acidosis) ● The ketone bodies are acid making your urine acidic
- electrolyte imbalance ● Decrease in NA
● Sariling katawan ang gumagawa ng mataas na insulin ● May cancer, pancreatic cancer ( beta cells) Exogenous ● Nasobrahan sa pag inject ng insulin sa katawan Endogenous ● Sobra dahil may sakit na cancer or tumor.
**5. Autoimmune hypoglycemia insulin autoantibodies
- Non-beta cell tumors** ● leukemia, hepatoma, lymphoma ● mesothelioma 7. Hypoglycemia of infancy or childhood ● galactosemia & other inborn errors of metabolism ● Reye's syndrome 8. Alimentary (reactive) hypoglycemia ● post-gastric surgery 9. Idiopathic (functional) ● postprandial hypoglycemia Inborn Errors of Carbohydrate Metabolism 1. Galactose metabolism ● abnormal galactose metabolism due to: a. Galactose-1-phosphate uridyl transferase deficiency ● associated with failure to thrive, prone to E. coli sepsis, liver dysfunction, impaired cognition, ataxic neurologic disease & ovarian failure in females b. Galactokinase deficiency ● associated with cataract formation & pseudotumor cerebri c. UDP-galactose-4-epimerase deficiency ● benign form limited to RBC & WBC disorders ● these enzymes are essential for the conversion of galactose to glucose & UDP-galactose which is needed for the formation of other carbohydrates ● detected by Newborn Screening Test Newborn Screening : ~ In the Philippines: ● Congenital Adrenal Hyperplasia (CAH)
- 21 hydroxylase deficiency ● Congenital Hypothyroidism (CH)
- Primary Congenital Hypothyroidism ● Glucose 6-Phosphate Dehydrogenase ● (G6PD) deficiency ● Galactosemia ● Phenylketonuria (PKU) 2. Fructose metabolism
- fructose intermediates are essential to glycolysis & gluconeogenesis
- 3 enzyme defects: a. Essential fructosuria b. Hereditary fructose intolerance c. Fructose-1,6-biphosphate deficiency 3. Glycogen Storage Diseases (GSD)
- Walang glycogen sa atay at sa laman ● inherited enzyme deficiencies that control the synthesis or breakdown of glycogen resulting in abnormal quality or quantities of glycogen ● primarily affects the liver & muscles ● hypoglycemia & hepatomegaly are associated with hepatic glycogenoses ● muscle cramps, exercise intolerance, fatigue, weakness are associated with muscle glycogenoses ● Hepatic glycogenoses: types I, III, IV, VI, IX, 0 ● Muscle glycogenoses: types V, VII. ● All are autosomal recessive except IXa which is X-linked
TABLE 2. GLYCOGEN STORAGE DISEASES
Ia Von Gierke Glucose-6-phosphate deficiency II Pompe 1,4 glucosidase deficiency IIIa Cori / Forbes Glycogen debranching enzyme deficiency IV Anderson’s Glycogen branching enzyme V Mc Ardle Muscle phosphorylase deficiency VI Hers Liver phosphate deficiency / glycogen phosphorylase deficiency VII Tarui Phosphofructokinase deficiency XI Fanconi Bickle Glucose-transporter-2 deficiency
● used for DM patients with GI disorders ● 0.5g of glucose per kg body weight is given within 3 mins intravenously Requirements for OGTT:
- Patient should be ambulatory
- Unrestricted CHO diet of 150g per day for 3 days prior testing
- No smoking or drinking alcohol prior testing
- Fasting for 6-8 hours
- Glucose load ● 75g or 100g; 1.75g of glucose per kg body weight for children (maximum of 75g) Procedure for OGTT:
- Fasting specimen is first collected, followed by drinking (within 5 mins)of 75g or 100g oral glucose load in 300-400ml water.
- Collect specimens after 1-hour, 2-hour, 3-hour.
- Patient should avoid exercise, eating, drinking & smoking during the test. 5 Glycosylated hemoglobin (HBA2C) ● is formed from the non-enzymatic, irreversible attachment of glucose to Hgb A 1 ● reflects the blood glucose levels for the past 2-3 months ● it is useful in monitoring effectiveness of treatment & compliance of diabetic individual to treatment protocol ● should be performed every 3-6 months in DM patients monitoring glycemic control
- Twice a year ● specimen is non-fasting EDTA collected blood ● affected by diseases associated with shortened red cell survival, hemolytic anemias ● reference value: 4.5%-6.5%; ● effective treatment range: <7% ● methods are: affinity chromatography, immunoassay, electrophoresis, HPLC
- Fructosamine ● it is known as glycosylated albumin/plasma protein ketoamine o Dito kumakapit ang sugar ● reflects blood glucose levels for 3-6 weeks o Short term lang kaya di pinapagawa ● it should not be measured in cases of hypoalbuminemia (<30g/L) ● reference value: 205-285 umol/L ● methods: affinity chromatography, HPLC, photoelectric
- Ketone bodies ● recommended when plasma glucose reached 300 mg/dL ● used to confirm diabetic ketoacidosis (DKA) ● specimen is fresh urine or serum ● Methods: o Sodium nitroprusside reaction: Acetoacetic acid + nitroprusside →
Purple color ● 3-hydroxybutyrate dehydrogenase ● Enzymatic: 3-B-hydroxybutyrate + NAD--- H+ NADH
- Microalbumin (Micral Test) ● useful to assist in diagnosis at an early stage & before the development of proteinuria (kidney function) ● performed on randomly collected urine specimens with simultaneous assay of creatinine ● recommended annually for DM patients ● specimen: urine ● persistent albuminuria: o 30-299 mg/g albumin to creatinine ratio in 2 out of 3 collections in 3- months
- C-peptide ● the amount of circulating C-peptide provides reliable indicators for pancreatic & insulin secretions ● it can be used to monitor individual responses to pancreatic surgery ● this mainly evaluates hypoglycemia & continuous assessment of beta cell function ● specimen: fasting serum ● increased in: insulinoma, type 2 DM, ingestion of hypoglycemic drugs ● decreased in: type 1 DM o Di naman gumagawa ng c-peptide ● reference value: 0.90-4.3 ng/mL o Tumataas ang C-peptide dahil sa endogenous (may sakit sa pancreatic) o Pancreas gagawin puro proinsulin o Kapag madaming C-peptide malalaman mo na madami nacoconsume na B-chain (proinsulin) Glucose methodologies: I. **Chemical Methods A. Oxidation-Reduction methods
- Alkaline Copper Reduction Method** ● principle: glucose ( a reducing agent) reduces cupric ions in alkaline solution forming cuprous oxide ● the solution loses its deep blue color & a red precipitate forms ● Benedict’s & Fehling’s regents
- which contain alkaline solution have been stabilized by citrate & tartarate respectively have been used to detect reducing agents in blood & urine. Alkaline Copper Tartarate → cuprous ions ● Folin Wu
- cuprous ions + phosphomolybdate to phosphomolybdenum blue ● Nelson-Somogyi
- cuprous ions + arsenomolybdate to arsenomolybdenum blue ● Neocuproine method
- cuprous ions + neocuproine (2, dimethyl 1,10 phenantroline hydrochloride) to cuprous-neocuproine complex (yellow or yellow orange) 2. Alkaline Ferric Reduction method (Hagedorn Jensen) ● involves the reduction of a yellow ferricyanide to a colorless ferrocyanide by glucose (inverse colorimetry) B. Condensation Method
- Ortho-toluidine method ● 630 nanometer ● principle: condensation with aromatic amines ● glucose in hot acetic solution condenses with aromatic amines forming glycosylamine & Shiff base (emerald green) ● classical method for measuring glucose Glucose + Aromatic Amines → glycosylamine + Schiff base
Lipids & Lipoproteins
Clinical Chemistry 1
BS Medical Technology BSMT 3-3 | Prof. Eric E. Carpo
LIPIDS & LIPOPROTEINS
● commonly referred to as fats , are classified as organic substances insoluble in blood & water but soluble in organic solvents (chloroform & ether).
- Biochemically, substance na di nalulusaw sa tubig ● Main Functions of Lipid/Fats ○ Provide rich source of energy & an efficient way for the body to store excess calories. ○ Provide stability to cell membrane & allow for transmembrane transport. ○ Important precursor of steroid hormones (testosterone, estrogen, aldosterone, progesterone), pain receptors (prostaglandins, leukotrienes) ■ Major classes of lipids:
- Fatty acids
- Cholesterol
- Triglycerides
- Phospholipids 1. Fatty Acids (FA) ● simplest lipid class, lipid building block or structural unit ● linear chains of carbon-hydrogen bonds that terminate with a carboxyl group ● Small amounts of fatty acids exist in the free or unesterified form bound to albumin ● Mostly found as constituents of phospholipids & triglycerides ● nearly always contain even number of unbranched C atoms ● characterized as: a. Long chain FA
- C 12 to C 26 b. Medium chain FA
- C 8 to C 10 c. Short chain FA
- C 4 to C 6 ● Classification: a. Saturated FA
- without C to C double bonds (all single bonds)
- Animal source b. Unsaturated FA
- with C to C double bonds
- Plant source (canola) 1. Monounsaturated FA
- has 1 double bond 2. Polyunsaturated FA
- has many double bonds Trans fat
- Causes coronary heart diseases
- butter, margarine 2. Cholesterol ● unsaturated steroid alcohol containing 4 rings & has a single carbon-hydrogen side chain tail similar to fatty acids ● Amphipathic molecule, meaning that the hydroxyl group in the A-ring is the hydrophilic part ● Found on the surface of lipid layers ● Functions: ○ precursor of steroid hormones- aldosterone, cortisol, testosterone, estrogen & progesterone
- Glucocorticoids, mineralcorticoids ○ provides stability to cell membrane ○ constituent of cell membrane & bile acids which emulsifies fats ○ can be transformed to vitamin D3 in the skin by sunlight ● diagnostic significance: ○ it evaluates the risk for atherosclerosis (blood cholesterol, naninikip sa ugat), myocardial & coronary arterial occlusions
specifically responsible for transporting lipid classes throughout the aqueous environment of the blood. ● Its main purpose is to transport TAG & cholesterol to sites of energy storage and utilization ● The protein provides a coat for lipid mixture, cholesterol & other lipids aggregate forming a large complex ● Carrier of lipids Apolipoprotein ● specialized proteins located on the surface of lipoprotein particles ● Functions:
- help maintain the structural integrity of the lipoprotein complex
- Help to keep the lipids in solution during circulation through the blood stream
- Serve as activators or inhibitors of enzymes involved in the synthesis or breakdown of fatty acid esters or lipids
- Interact with specific cell-surface receptors & direct the lipids to the correct target organs & tissues in the body **Table 1. Lipoproteins & Apolipoproteins (MAJOR LIPOPROTEINS) Lipoprotein Remarks
- Chylomicron (CM)** ● produced by the intestines ● Largest & least dense produced by the intestine that transports lipids of dietary origin to the tissues of the body including the liver ● transports dietary/exogenous TAG to target tissues ● TAG rich but relatively poor in free cholesterol, phospholipids & protein ● Apolipoproteins ○ Apo B-
- Maintains structural integrity ○ Apo A-1, Apo C, Apo E ● Major Apolipoprotein ○ Apo B- 2. Very Low Density Lipoprotein (VLDL) ● Produced by the liver & supply the tissues of the body with TAG of endogenous origin ● transports endogenous TAG to target tissues ● rich in TAG but to a lesser extent than CM ● Have a higher buoyant density because of their lowest lipid/protein ratio ● Prolonged consumption of high-fat diet leads to elevated TAG & VLDL ● Apolipoproteins: ○ Apo B- ○ Apo C ○ Apo E ● Major Apolipoprotein ○ Apo B- 3. Low Density Lipoprotein (LDL) ● Synthesized by the liver ● major end product of VLDL catabolism ● Constituents 50% of the total lipoprotein mass in human oplasma ● Major source of cholesterol for tissues ● transports cholesterol ● most cholesterol-rich of the lipoprotein & most atherogenic in fastubf okasma samples, LDL contains the cholesterol that is not present in HDL or VLDL ● also known as “BAD” cholesterol ● It transports cholesterol to the peripheral tissue
● Apolipoprotein ○ Apo B-100, Apo E ● Major Apolipoprotein ○ Apo B-
4. High Density Lipoprotein (HDL) ● produced in the liver & intestine ● smallest but most dense, about 50% protein ● involved in reverse cholesterol transport, transports excess cholesterol from the tissues & return it to the liver ● HDL 2 transports effectively the lipids to the liver & is cardioprotective ● it is involved in anti-inflammatory, anti-oxidant, anti-thrombotic & nitric oxide inducing mechanisms ● thus the “GOOD” cholesterol ● Apolipproteins ○ Apo A-I, Apo A-II, Apo C ● Major Apolipoprotein ○ Apo A-I ● Kapag may highblood, constriction VDL and IDL
- Stroke
- Atake sa puso
- Pulmonary formation (peripheral artery disease) **Minor Lipoproteins
- Intermediate Density Lipoproteins (IDL)** ● product of VLDL catabolism- “VLDL remnant” ● converted to LDL- “subclass of LDL” ● defective clearance of IDL in Type 3 Hyperlipoproteinemia is probable due to deficiency of Apo E-III ● major apolipoprotein: ○ Apo B- ● We can't measure IDL because we dont have accurate method 2. Lipoprotein (a) ● similar to LDL in density & composition ● contains a molecule of Apo (a) linked to Apo B-100 by disulfide bond ● known as “sinking pre-beta lipoprotein” ● increased levels may indicate premature coronary heart disease & stroke ● independent risk factor for atherosclerosis ● Apolipoproteins ○ Apo B-100, Apo (a) Table 2. Major Lipoproteins & their Composition Lipopr otein TAG Cholest erol Ester Free Chole sterol Protein Phosph olipid CM 80-95% 2-4% 1-3% 1-2% 3-6% VLDL 45-65% 16-22% 4-8% 6-10% 15-20% LDL 4-8% 45-50% 6-8% 18-22% 18-24% HDL 2-7% 15-20% 3-5% 45-55% 26-32% **Abnormal Lipoproteins
- Lipoprotein X** ● abnormal lipoprotein found in obstructive jaundice & lecithin cholesterol acyltransferase (LCAT) deficiency
- Obstruction sa liver ● Lipids account for more than 90% of its weight ● proteins such as Apo C & albumin constitute the 10% ● Cannot be measure in laboratory 2. Beta-VLDL (floating beta lipoprotein) ● abnormal lipoprotein that
