Lipids (diseases and vitamins) Flashcards
What are the sources of vitamin B12?
- Microbiota
- Liver
- Fish
- Red meat
- Eggs
- Dairy
- Fortified grains
What are the functions of vitamin B12?
- 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
What are the results of vitamin B12 deficiency?
- 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
What are the functions of folate?
Transfer of one-carbon units from Ser, Gly, or His during:
- Synthesis of some AAs
- Synthesis of purines and TMP
What are the causes of folate deficiency?
- Chemotherapeutic drugs, e.g. methotrexate
- Increased requirements (e.g. during pregnancy)
- A folate-free diet
What are the results of folate deficiency?
- Neural tube defects in fetuses (namely spina bifida, anencephaly)
- Megaloblastic anemia (erythropoietic cells grow but cannot divide due to deficiency in TMP)
What is the minimum daily requirement of folate?
400 µg per day
What is the precursor of the vitamin A forms?
β-carotene
What is the active form of vitamin A?
Retinoic acid, except in spermatogenesis (retinol and retinal) and for vision (11-cis-retinal)
What are the functions of vitamin 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
What are the sources of vitamin A?
- Preformed vitamin A: liver, kidney, butter, egg yolk
- As β-carotene: yellow, orange, or dark-green fruits and vegetables
What are the symptoms of vitamin A deficiency?
- 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)
What is the upper limit for vitamin A?
- As vitamin A: >3 mg per day
- As retinol: >7.5 mg per day
What are the symptoms of vitamin A toxicity?
- 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
What are the forms of vitamin D?
- Ergocalciferol (D2): from plants
- Cholecalciferol (D3): from animals or synthesized in skin
- Calcidiol (25-hydroxycholecalciferol)
- Calcitriol (1,25-dihydroxycholecalciferol): active form
How is the active form of vitamin D synthesized in the body?
(1) ergocalciferol/cholecalciferol → calcidiol (25-hydroxylase)
(2) calcidiol → calcitriol (1-hydroxylase)
What are the functions of vitamin D?
- 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
What are the exogenous sources of vitamin D?
- Fatty fish
- Liver
- Egg yolk
- Fortified milk
What is the daily recommended intake of vitamin D?
- 15 µg (600 IU) per day for ages 1–70
- 20 µg (800 IU) per day for ages 70 and above
What is the upper limit of vitamin D?
100 µg (4,000 IU) per day
What are the symptoms of vitamin D toxicity?
- Nausea
- Anorexia
- Thirst
- Bone resorption
- Deposition of calcium in tissues
What are the forms of vitamin K?
- Phylloquinone (K1): plants
- Metaquinone (K2): intestinal microbiota
- Menadione (K3): synthetic compound
What are the natural sources of vitamin K?
- Microbiota
- Cabbage
- Spinach
- Egg yolk
- Liver
What are the functions of vitamin K?
- 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
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
What are the symptoms of vitamin K toxicity?
- Hemolytic anemia
- Jaundice
What is the function of vitamin E?
Antioxidant
What are the features of type I hyperlipoproteinemia?
- Deficiency in lipoprotein lipase or Apo C-II
- Leads to increased plasma levels of chylomicron-TAG
What are the features of type IIa hyperlipoproteinemia?
Deficiency in LDL receptor
What are the features of Wolman disease?
- Autosomal recessive
- Deficiency in lysosomal acid lipase, leading to accumulation of cholesteryl esters and TAGs
What are the features of Niemann–Pick disease, type C?
- Autosomal recessive
- Deficient transport of free cholesterol out of lysosomes
What are the features of Tangier disease?
Absence of ABCA1
What are the features of type III hyperlipoproteinemia?
Mutated apoE, leading to decreased binding of chylomicron remnants to receptors
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
Where does the drug ezetimibe act?
Blocks the protein NPC1L1 involved in intestinal uptake of cholesterol
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
How do statins function?
Structural analogs of HMG, competitively inhibit cytosolic HMG CoA reductase
What are the features of Tay–Sachs disease?
- Autosomal recessive
- Deficient β-hexoseaminidase
- Accumulation of GM2 in lysosomes, leading to rapid neurodegeneration
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
What are the features of Niemann–Pick disease, types A and B?
- Autosomal recessive
- Deficienct sphingomyelinase
- Fatty liver, hepatomegaly, mental retardation
What are the features of Farber disease?
- Autosomal recessive
- Deficient ceramidase
- Joint deformity, nodules of lipid laden cells, hoarse cry
What are the features of Fabry disease?
- X-linked
- ERT available
How are sphingolipidoses diagnosed?
- DNA analysis
- Testing enzyme activity in fibroblasts or leukocytes
What are the features of Refsum disease?
- Autosomal recessive
- Deficiency in phytanoyl CoA hydroxylase (PhyH)
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
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
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
