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Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia
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Abetalipoproteinemia

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AUCMS MD AUCMS Sem-1 SGD Presentation

AUCMS MD AUCMS Sem-1 SGD Presentation

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  • 1. CASE:ABETALIPOPROTEINEMIA GROUP 2; SUBGROUP 1 MEMBERS: •ARWIN NAMBIYAR A/L NANDAKUMAR •AFIQ HIDAYAT BIN ADLAN SUHAIMI •MOHAMAD HAZLIYUDIN BIN ZAIDI •KANAGESWARI A/P SATIANARAINAN •DAYANG NUR SHARMILA BINTI MOHD YUSOF •HANISAH BT AHMAD LATFI •MUHAMMAD NURHADI B BASHIR MOHAMAD •NUR ATIKAH BINTI BIDIN
  • 2. 1. What AreLipoproteins?
  • 3. LIPOPROTEINS• A biochemical assembly containing both – Lipid – Protein• The lipids or their derivatives may be covalently or non-covalently bound to the proteins• Important constituents of biologic membranes and of myelin.• Classified into types/classes based on their density or constituent of apolipoproteins.• Act as transport vehicles for cholesterol and triglyceride transport throughout the body.
  • 4. A plasma lipoproteins are usually;• Spheric,• each lipoproteins have 5 components which consist of; – a hydrophobic core of; • triacylglycerides, • cholesteryl esters, – and surrounded by • Apoprotein • Cholesterol • Phospholipids.• The amount of each component will vary depending on the lipoprotein being discussed.
  • 5. 2. Different Types Of Lipoproteins.
  • 6. CHYLOMICRON VLDL TYPES OFLIPOPROTEIN IDL LDL HDL kana
  • 7. kana
  • 8. CHYLOMICRON• Largest and most buoyant class.• <0.95 g/mL• Apo B-48.• Are formed in the intestine• Triglycerides –dietary origin kana
  • 9. Very low density lipoprotein• Largest lipoprotein• 0.95-1.006 g/mL• Apo B-100• Containing endogenously produced lipids• Triglycerides – endogenous in origin kana
  • 10. Intermediate density lipoprotein• Produced during conversion of VLDL to LDL.• 1.006-1.019 g/mL• APO B-100• Cholesteryl ester and triglycerides kana
  • 11. LOW DENSITY LIPOPROTEIN• Major cholesterol containing lipoprotein• End product of VLDL• 1.019-1.063 g/mL• Apo B-100• Mainly comprise cholesteryl esters kana
  • 12. High Density Lipoprotein• Smallest and most dense of the lipoprotein• HDL₂ (1.063-1.12 g/mL) and HDL₃ (1.12-1.21 g/mL)• A-1• HDL₃ are smaller and denser than HDL₂ . kana
  • 13. 3. Relation between theFunctions of Lipoproteins and their Structure
  • 14. General Structure Of Lipoprotein
  • 15. CHOLESTEROL CHOLESTEROL(DEGRADES INTO LDL) DIETARY TRIGLYCERIDE NEWLY SYNTHESIZED TRIGLYCERIDE
  • 16. 4. What AreApolipoproteins and their Importance As A Component Of Lipoprotein?
  • 17. • Apolipoproteins are proteins that bind with lipids (oil-soluble substances such as fat and cholesterol) to form lipoproteins.• There are 6 classes of apolipoproteins and several sub-classes:1. A (apo A-I, apo A-II, apo A-IV, and apo A-V)2. B (apo B48 and apo B100)3. C (apo C-I, apo C-II, apo C-III, and apo C-IV)4. D5. E6. H
  • 18. Two major types of apolipoproteins:1. Apolipoproteins B form low-density lipoprotein(LDL), "bad cholesterol" particles. These proteins have mostly beta- sheet structure and associate with lipid droplets irreversibly.2. Other apolipoproteins form high-density lipoprotein(HDL), "good cholesterol" particles. These proteins consist of alpha-helices and associate with lipid droplets reversibly.
  • 19. • Apolipoproteins also serve as enzyme cofactors, receptor ligands, and lipid transfer carriers that regulate the metabolism of lipoproteins.• In particular, apoA1 is the major protein component of high-density lipoproteins(HDL).• apoA4 is thought to act primarily in intestinal lipid absorption.• Apolipoprotein transport the lipids through the lymphatic and circulatory systems.• Ligands for interaction with lipoprotein receptors in tissues ( apoB100 and apoE for LDL- receptors, apoA-I for HDL receptors).
  • 20. WHAT ISABETALIPOPROTEINEMIA?
  • 21. ABETALIPOPROTEINEMIA• Is a disorder of lipoprotein assembly inherited as an autosomal recessive trait characterized by the near absence of APOLIPOPROTEINS B and apoB-containing lipoproteins in plasma.• Deficient or absence of Microsomal Triglyceride Transfer Protein (MTTP) in enterocytes suggest the defect in lipoprotein assembly in which it affect the apoB packaging that results in lipid non-release and degradation and non- production of apoB in the intestines and liver.• This beta-lipoprotein are essential for carrying; – Fats – Fat-like substances mello
  • 22. 5. Role Of MTP In Lipoprotein Assembly And How The Absence of MTP Activity Affect The Secretion OfChylomicrons, VLDL And LDL.
  • 23. Question5.1 Discuss the role of MTP in Lipoprotein assembly ?5.2 Why & How would be the absence of MTP activity affect the packaging of ApoB ?
  • 24. 5.1 : The role of MTP in Lipoprotein assembly• Facilitates the transfer of cholyesteryl esters ,phospholipid and trygliceride• From the endoplasmic reticulum to apoB• Enabling apoB to detach from the membrane of the endoplasmic reticulum
  • 25. 5.2 : the absence of MTP activity affect the packaging of ApoB.o Why ?  There is a point mutation(Nonsense Mutation) occur on chromosome 4 in position 24 in long part chromosome
  • 26. • How? – apoB cannot be packaged with lipid and therefore cannot be released from the endoplasmic reticulum membrane – Therefore ,preventing chylomicron ,VLDL and LDL from being secreted – It answers the girl were suffering Abetalipoproteneima
  • 27. “…The PATIENT’S PARENTS WHO AREIN GOOD HEALTH BOTH HAD NORMAL LEVEL OF APOB.” BUT WHY?
  • 28. 6. Clinical Manisfestation Of Patient With Abetalipoproteinemia
  • 29. CLINICAL MANIFESTATIONFAT MALABSORPTION FAT-SOLUBLE DEFICIENCIES (VITAMIN A, E, K) HEMOTOLOGIC ABNORMALITITES
  • 30. FAT MALABSORPTION• Often misdiagnosed as celiac disease• Inability of small intestine to absorb fats• Due to inability production of the apoB, any absorbed fat cannot be secreted into lymphatic system• Thus, causing lipid engorgement of the enterocytes of the small intestine
  • 31. • Since fat is hydrophobic, they cannot be directly secreted but are secreted as a complex with apoB-containing lipoproteins. ApoB acts like a detergent in maintaining the solubility of lipids in plasma.
  • 32. FAT-SOLUBLE DEFICIENCIES• VITAMIN A - decrease night vision• VITAMIN K - cause prolonged prothrombin time - develop hemostasis (stoppage of blood flow) - necessary for the synthesis of several coagulation factors (factors II, VII, IX, and X)
  • 33. • Vitamin E - Affected in 3 steps in the pathway of vitamin E absorption1st pathway :First, along with other fat soluble vitamins, the fatmalabsorption decreases the absorption of vitamin E 2nd pathway Second, the small amount of vitamin E that may be absorbed can not be efficiently secreted by the intestine because of the defect in the chylomicron secretion. 3rd pathway Third, any vitamin E that is delivered to the liver also can not be secreted because of the defect in the VLDL secretion.
  • 34. • The deficiency is also due to defect in the tocopherol binding protein (TBP) to extract vitamin E from the blood
  • 35. HEMATOLOGIC ABNORMALITIES• Presence of acanthocytes• Acanthosytes are abnormally formed red blood cells and have a ‘star-shape’ appearance.• Decreased level of plasma cholesterol leads to an abnormal cholesterol: phospholipid ratio in the plasma membrane• Cause anaemia and compensatory reticulocytosis (increased production of red blood cells)• Due to abnormal shape of the red blood cell, the sedimentation rate (the rate of red cell sedimentated during centrifugation) decreases
  • 36. 7. Why IsAbetalipoproteinemia Associated With Fat- soluble Vitamin Deficiency? mello
  • 37. CASE STUDY• From the physical examination the patient is experiencing; – Decreased tendon reflexes – Gait ataxia – Rhomberg sign – Bilateral pigmented retinopathy• Lab Investigation shows; – Slightly prolonged prothrombin time – Decreased hematocrit – Numerous acanthocytes – Increased reticulocyte count – Decreased erythrocyte sedimentation rate – Absence of apoB, VLDL and LDL
  • 38. • Our body needs a sufficient levels of, fats cholesterol vitaminsare necessary for, normal growth development maintenance of the bodys cells and tissues, particularly nerve cells and tissues in the eye.• Due to the inability to make beta- lipoproteins, the absorption of dietary fats and fat-soluble vitamins (Vitamin A, E and K) from the digestive tract to the bloodstream will be mello disrupted.
  • 39. • From the case study, we can imply that the patient is having significant deficiency of; – Essential Dietary Fats : causing deformity of red blood cells. – Vitamin A : affecting the night vision. – Vitamin E : causing some CNS complication. – Vitamin K : affects the blood clotting ability.• Patients with abetalipoproteinemia develop severe vitamin E deficiency because they are affected in three steps pathways as explained from the previous question. mello
  • 40. • Vitamin A and K are also packaged into chylomicrons after absorption from the lumen of the intestine• But unlike vitamin E , they are not fully dependent on VLDL for their transport.• The absorption of these vitamins is affected only at steps 2 and 3 in the pathways.• That’s why deficiency of these fat soluble vitamins are not severe. mello
  • 41. 7.2. Why do patients with this disorder do not develop vitamin D deficiency? • Vitamin D is required for; – bone maintenance and bone synthesis – It maintains the levels of calcium and phosphorus in the blood to regulate bone growth – also part of cells in the immune system, brain, pancreas, skin, muscles, cartilage and reproductive organs. • Some vitamin D is supplied by the diet, but most of it is made in the body. • That’s why vitamin D deficiency is not manifested in this disorder because it is not solely dependant on lipoproteins to transfer it throughout the body. mello
  • 42. How Vitamin D is made in the body Consumption of Sterol are stored in sterol (provitamin) Exposure to UV light the liver from food source. undergoes its first Vitamin D is bound Modification of hydroxylation into to vitamin-D binding chemical structure of 25-hydroxyvitamin protein in the blood Vitamin D via the D, and stored in the and carried to the skin tissues liver liver parathyroid hormone is produced and increases Will be hydroxylated tubular absorption of Travels to small into 1,25 (OH) 2D in calcium and renal intestine increases kidney, when there is production of the efficiency of a calcium deficiency 1,25(OH)2D. calcium absorption mello
  • 43. 8. Why Are The Intestinal AndHepatic Cells Accumulating Fats In Abetalipoprotenemia Disorder?
  • 44. WHAT IS ABETALIPOPROTEINEMIA????Abetalipoproteinemia is a rare autosomalrecessive disorder that interferes with thenormal absorption of fat and fat-solublevitamins from food.
  • 45. • Abetalipoproteinemia affects the absorption of dietary fats, cholesterol, and certain vitamin.• People affected by this disorder are not able to make lipoproteins, which are molecules that consist of proteins combined with cholesterol and particular fats called triglycerides.• This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A, vitamin D, vitamin E and vitamin K. However, many of the observed effects are due to vitamin E deficiency in particular.
  • 46. Micrograph showingenterocytes with aclear cytoplasm (due tolipid accumulation)characteristic ofabetalipoproteinemia.
  • 47. • Fats are mostly accumulated in the intestinal cell of intestine and hepatic cells of liver due to the absence of MTTP gene that responsible to produce apo B in transporting the fats(lipids) in form of lipoprotein.• This will lead to atherosclerosis disorder
  • 48. 9. What Other Disorder May Arise From Derangements OfLipoprotein Dysfunction?
  • 49. CHYLOMICRON RETENTION DISEASE
  • 50. CHYLOMICRON
  • 51. WHAT’S GOING ON WITH THE CHYLOMICRON RETENTION DISEASE PATIENT??? Mutation in SAR1B gene Who is SAR1B gene???The gene provides instructions for making a protein, called SAR1B that is involved in transporting chylomicrons within enterocytes.
  • 52. enterocytes
  • 53. enterocytes
  • 54. HOW?SAR1B gene mutations will cause the protein SAR1B to impair the release of CHYLOMICRONS into the bloodstream. as we all know that… Chylomicrons are important because… .
  • 55. SO…lack of chylomicrons in the blood will… prevent dietary fats and fat-soluble vitamins from being used by the body, Consequence: nutritional and developmental problems CHYLOMICRON RETENTION DISEASE
  • 56. Chylomicron Retention Diseasepatients have the following symptoms: • failure to gain weight and grow at the expected rate; • decreased reflexes (hyporeflexia) • Diarrhea • fatty, foul-smelling stools (steatorrhea). • decreased ability to feel vibrations
  • 57. THANK YOU

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