Lipids (diseases and vitamins) Flashcards
1
Q
What are the sources of vitamin B12?
A
- Microbiota
- Liver
- Fish
- Red meat
- Eggs
- Dairy
- Fortified grains
2
Q
What are the functions of vitamin B12?
A
- Participate in β-oxidation of odd-numbered fatty acids
- Coenzyme for the methylation of homocysteine to methionine, which also results in the conversion of methyl-H4-folate to methylene-H4-folate for thymidine synthesis
3
Q
What are the results of vitamin B12 deficiency?
A
- Branched AAs accumulate, leading to neurologic manifestations
- Accumulation of homocysteine
- Pernicious anemia, likely due to immune-mediated destruction of gastric parietal cells and a decrease in intrinsic factor, which is required for absorption of B12 in the intestine
- Achlorhydria in elderly patients
4
Q
What are the functions of folate?
A
Transfer of one-carbon units from Ser, Gly, or His during:
- Synthesis of some AAs
- Synthesis of purines and TMP
5
Q
What are the causes of folate deficiency?
A
- Chemotherapeutic drugs, e.g. methotrexate
- Increased requirements (e.g. during pregnancy)
- A folate-free diet
6
Q
What are the results of folate deficiency?
A
- Neural tube defects in fetuses (namely spina bifida, anencephaly)
- Megaloblastic anemia (erythropoietic cells grow but cannot divide due to deficiency in TMP)
7
Q
What is the minimum daily requirement of folate?
A
400 µg per day
8
Q
What is the precursor of the vitamin A forms?
A
β-carotene
9
Q
What is the active form of vitamin A?
A
Retinoic acid, except in spermatogenesis (retinol and retinal) and for vision (11-cis-retinal)
10
Q
What are the functions of vitamin A?
A
Acts as a transcription factor for several genes, modulating:
- Reproduction: spermatogenesis and prevention of fetal resorption (retinol and retinal)
- Growth in children: retinoic acid
- Maintenance of epithelia: retinoic acid
- Vision: 11-cis-retinal
11
Q
What are the sources of vitamin A?
A
- Preformed vitamin A: liver, kidney, butter, egg yolk
- As β-carotene: yellow, orange, or dark-green fruits and vegetables
12
Q
What are the symptoms of vitamin A deficiency?
A
- Mild: nyctalopia (night blindness)
- Prolonged: irreversible ophthalmic damage
- Severe: xerophthalmia (dryness of cornea and conjunctiva, followed by scarring and blindness); acne and psoriasis (treatable with vitamin A administration)
13
Q
What is the upper limit for vitamin A?
A
- As vitamin A: >3 mg per day
- As retinol: >7.5 mg per day
14
Q
What are the symptoms of vitamin A toxicity?
A
- Teratogenesis in pregnant women
- If due to isotretinoin (a drug used for acne) toxicity: increased levels of TAGs and cholesterol, with risk of coronary heart disease
15
Q
What are the forms of vitamin D?
A
- Ergocalciferol (D2): from plants
- Cholecalciferol (D3): from animals or synthesized in skin
- Calcidiol (25-hydroxycholecalciferol)
- Calcitriol (1,25-dihydroxycholecalciferol): active form
16
Q
How is the active form of vitamin D synthesized in the body?
A
(1) ergocalciferol/cholecalciferol → calcidiol (25-hydroxylase)
(2) calcidiol → calcitriol (1-hydroxylase)
17
Q
What are the functions of vitamin D?
A
- Regulation of serum levels of phosphate and calcium
- Low phosphate levels directly upregulate 1-hydroxylase
- Low calcium levels indirectly upregulate 1-hydroxylase via action of parathyroid hormone
- Calcitriol acts by negative feedback to decrease parathyroid hormone levels
18
Q
What are the exogenous sources of vitamin D?
A
- Fatty fish
- Liver
- Egg yolk
- Fortified milk
19
Q
What is the daily recommended intake of vitamin D?
A
- 15 µg (600 IU) per day for ages 1–70
- 20 µg (800 IU) per day for ages 70 and above
20
Q
What is the upper limit of vitamin D?
A
100 µg (4,000 IU) per day
21
Q
What are the symptoms of vitamin D toxicity?
A
- Nausea
- Anorexia
- Thirst
- Bone resorption
- Deposition of calcium in tissues
22
Q
What are the forms of vitamin K?
A
- Phylloquinone (K1): plants
- Metaquinone (K2): intestinal microbiota
- Menadione (K3): synthetic compound
23
Q
What are the natural sources of vitamin K?
A
- Microbiota
- Cabbage
- Spinach
- Egg yolk
- Liver
24
Q
What are the functions of vitamin K?
A
- Carboxylation of Glu residues in coagulation factors, leading to their attachment to platelets
- Warfarin inhibits the vitamin K epoxide reductase needed for regeneration of vitamin K, acting as an anticoagulant
25
What are the causes of vitamin K deficiency?
* Use of some antibiotics (e.g. cefamandole)
* In newborns: sterile intestine, breast milk is a poor source
* Newborns are given an IM shot of vitamin K for prophylaxis against hemorrhagic disease
26
What are the symptoms of vitamin K toxicity?
* Hemolytic anemia
* Jaundice
27
What is the function of vitamin E?
Antioxidant
28
What are the features of type I hyperlipoproteinemia?
* Deficiency in *lipoprotein lipase* or Apo C-II
* Leads to increased plasma levels of chylomicron-TAG
29
What are the features of type IIa hyperlipoproteinemia?
Deficiency in LDL receptor
30
What are the features of Wolman disease?
* Autosomal recessive
* Deficiency in lysosomal *acid lipase*, leading to accumulation of cholesteryl esters and TAGs
31
What are the features of Niemann–Pick disease, type C?
* Autosomal recessive
* Deficient transport of free cholesterol out of lysosomes
32
What are the features of Tangier disease?
Absence of ABCA1
33
What are the features of type III hyperlipoproteinemia?
Mutated *apoE*, leading to decreased binding of chylomicron remnants to receptors
34
What are the isoforms of Apo E?
* Apo E-2: binds poorly, leads to type III hyperlipoproteinemia and premature atherosclerosis
* Apo E-3: normal
* Apo E-4: risk of early-onset Alzheimer disease
35
Where does the drug *ezetimibe* act?
Blocks the protein NPC1L1 involved in intestinal uptake of cholesterol
36
What is the result of defects in the protein ABCG5/G8?
Decreased pumping of cholesterol out of the intestine, leading to sitosterolemia and increased risk of MI
37
How do statins function?
Structural analogs of HMG, competitively inhibit cytosolic *HMG CoA reductase*
38
What are the features of Tay–Sachs disease?
* Autosomal recessive
* Deficient β-hexoseaminidase
* Accumulation of GM2 in lysosomes, leading to rapid neurodegeneration
39
What are the features of Gaucher disease?
* Autosomal recessive
* Most common lysosomal storage disease
* Deficient β-galactosidase
* Treatment: ERT, substrate reduction, or bone marrow transplantation
40
What are the features of Niemann–Pick disease, types A and B?
* Autosomal recessive
* Deficienct sphingomyelinase
* Fatty liver, hepatomegaly, mental retardation
41
What are the features of Farber disease?
* Autosomal recessive
* Deficient ceramidase
* Joint deformity, nodules of lipid laden cells, hoarse cry
42
What are the features of Fabry disease?
* X-linked
* ERT available
43
How are sphingolipidoses diagnosed?
* DNA analysis
* Testing enzyme activity in fibroblasts or leukocytes
44
What are the features of Refsum disease?
* Autosomal recessive
* Deficiency in phytanoyl CoA hydroxylase (PhyH)
45
What are the features of MCAD deficiency?
* Autosomal recessive
* Prevalent in Northen Europeans
* Decreased utilization of MCFAs
* Severe fasting hypoglycemia and hypoketemia
* Treated by avoiding fasting
46
What are the features of primary carnitine deficiency?
* Defect in a transporter for uptake of carnitine into skeletal and cardiac muscle
* Carnitine is excreted in urine
* Treated by supplementation
47
What are the features of secondary carnitine deficiency?
* Caused by certain drugs (e.g. valproic acid, an antiepileptic), decreased renal resorption, or decreased liver synthesis (due to hepatic disease, for example)
* Defective β-oxidation, carnitine–LCFA buidls up and is excreted in urine
* CPT-I deficiency affects the liver, leading to fasting hypoglycemia, coma, and death
* CPT-II deficiency affects liver, skeletal muscle, and cardiac muscle
* Treated by avoiding fasting
