The patient is part of a group project studying lipoproteins. Lipoproteins are biochemical assemblies containing lipids and proteins that transport cholesterol and triglycerides around the body. There are different types of lipoproteins classified by density, including chylomicrons, VLDL, IDL, LDL, and HDL. Apolipoproteins are important protein components of lipoproteins that help package and transport lipids. Abetalipoproteinemia is a rare genetic disorder where patients cannot produce apolipoprotein B or apoB-containing lipoproteins, leading to an inability to absorb dietary fats and fat-soluble vitamins. This causes symptoms like fat malabsorption, fat-soluble vitamin deficiencies,

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 Are
Lipoproteins?

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 OF
LIPOPROTEIN IDL
LDL
HDL
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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 the
Functions of Lipoproteins
and their Structure

14. General Structure Of Lipoprotein

15. CHOLESTEROL
CHOLESTEROL
(DEGRADES INTO LDL)
DIETARY TRIGLYCERIDE
NEWLY SYNTHESIZED TRIGLYCERIDE

16. 4. What Are
Apolipoproteins 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. D
5. E
6. 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 IS
ABETALIPOPROTEINEMIA?

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 Of
Chylomicrons, VLDL And LDL.

23. Question
5.1 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

26. 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

27. • 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

28. “…The PATIENT’S PARENTS WHO ARE
IN GOOD HEALTH BOTH HAD NORMAL
LEVEL OF APOB.”
BUT WHY?

30. 6. Clinical Manisfestation
Of Patient With
Abetalipoproteinemia

31. CLINICAL
MANIFESTATION
FAT MALABSORPTION
FAT-SOLUBLE
DEFICIENCIES
(VITAMIN A, E, K)
HEMOTOLOGIC
ABNORMALITITES

32. 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

33. • 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.

34. 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)

35. • Vitamin E
- Affected in 3 steps in the pathway of vitamin E
absorption
1st pathway :
First, along with other fat soluble vitamins, the fat
malabsorption 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.

36. • The deficiency is also due to defect in the
tocopherol binding protein (TBP) to extract
vitamin E from the blood

37. 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

38. 7. Why Is
Abetalipoproteinemia
Associated With Fat-
soluble Vitamin
Deficiency?
mello

39. 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

40. • Our body needs a sufficient levels of,
fats
cholesterol
vitamins
are necessary for,
normal growth
development
maintenance of the body's 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.

41. • 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

42. • 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

43. 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

44. 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

45. 8. Why Are The Intestinal And
Hepatic Cells Accumulating Fats
In Abetalipoprotenemia
Disorder?

46. WHAT IS ABETALIPOPROTEINEMIA????
Abetalipoproteinemia is a rare autosomal
recessive disorder that interferes with the
normal absorption of fat and fat-soluble
vitamins from food.

47. • 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.

48. Micrograph showing
enterocytes with a
clear cytoplasm (due to
lipid accumulation)
characteristic of
abetalipoproteinemia.

49. • 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

50. 9. What Other Disorder
May Arise From
Derangements Of
Lipoprotein Dysfunction?

51. CHYLOMICRON RETENTION
DISEASE

52. CHYLOMICRON

53. 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.

54. enterocytes

55. enterocytes

56. 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…
.

57. 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

58. Chylomicron Retention Disease
patients 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

61. THANK YOU