Dai3-Heme Flashcards
What is Methylmalonic acidemia (aciduria) MMA?
- Deficiency in methylmalonyl CoA mutase
- Accumulation of methylmalonic acid
- May interfere with myelination of nervous tissues
- Accumulation of metabolic intermediates produced from Met, Val, Ile, and Thr
- TREATMENT: diet low in Met, Val, Ile, Thr; B12
What is the importance of Folic acid deficiency?
-Most common vitamin deficiency
-Normal requirement: 100 – 200 μg/day
-Causes: inadequate intake, impaired absorption, impaired metabolism (e.g. use of methotrexate,
inhibitor of DHF reductase), increased demand
-Defective purine/thymidine synthesis -> hematopoietic defects (anemia)
-Defective glycine cleavage (neurological defects)
-Defective homocys -> hyperhomocysteinemia -> neurological defects
What are the pathological consequences of folic acid deficiency?
- Altered appearance of blood cells
- Anemia
- Neurological symptoms: irritability, forgetfulness
What are the causes of Vitamin B12
(cobalamin) deficiency ?
- Not enough B12; in animal-derived foods
- Can be stored in liver for years
- Impaired absorption is more common, due to defect in Intrinsic factor (IF)
- -> made by stomach parietal cells- required for transport and absorption of B12
What is Pernicious anemia?
- Autoimmune destruction of gastric parietal cells that produces IF
- Hematopoietic defects (megaloblastic anemia)
- Neurological defects
Treatment: - IM injection of B12, or high dose of B12 orally
- Folate supplement bc it can alleviate hematopoietic defects
What are the Biochemical consequences of B12 deficiency ?
- Defective methylmalonyl CoA to succinyl CoA
conversion (methylmalonic acidemia) - Defective homocys to methionine conversion
(hyperhomocysteinemia), neurological defects - Defective THF regeneration leading to defective purine/pyrimidine synthesis, hematopoietic defects
What is heme and its functions?
- A porphyrin, constituent of hemoglobin, myoglobin, cytochromes, and catalase. Functions: - binds oxygen (hemoglobin) - electron carrier (cytochrome) - part of active site (catalase)
Where does heme biosynthesis occur?
- Mitochondria (1st step)
- Cytosol (formation of porphyrin)
- Mitochondria (formation of heme)
What is AIP (Acute Intermittent Porphyria)?
- Autosomal dominant deficiency of PBG deaminase -> accumulation of PBG & ALA in urine and serum, which is NEUROTOXIC
- “Attacks”: abdominal pain, depression, neuropathy, anxiety, paranoia. Triggered by infections, some drugs, fasting, stress, acidosis, and hormonal changes
- Treatment: glucose, intravenous heme injection, high-carb diet, avoid drugs, treat infections
What is PCT (Porphyria Cutaneous Tarda)?
- Defect in uropor. decarboxylase –> accumulation of uropor III in the skin, where it oxidizes to uroporphyrin causing PHOTOSENSITIVITY
- Sunlight makes porphyrins release free radicals
- Scarring, bullaes, irregular pigmentation
- Red-wine color urine bc of uroporphyrins
- Treatment: avoid sun & alcohol, Chloroquine (complexes porphyrins for excretion), B-carotene ingestion (free radical scavenger)
What are the main steps in heme degradation & excretion?
1) RBCs are in macrophages release herme
2) Heme–> biliverdin–> bilirubin
3) Bilirubin-Albumin travels & is taken up by liver
4) Bilirubin conjugated –> bilirubin diglucuronide
5) Secreted into bile
6) Bacteria in intestine converts it back to unconjugated bilirubin
7) Bilirubin oxidized –> urobilinogen
8) Urobilinogen –> stercobolin (feces) & urobilin (urine)
What is jaundice?
- Yellow pigmentation of skin and eye’s whites due to bilirubin deposition. Can be due to:
1) Excess hemolysis (more bilirubin produced)
2) Liver damage (decreased bilirubin uptake and decreased secretion)
3) Bile duct obstruction (decreased secretion of bilirubin bc it correlates with bile flow)
What is neonatal jaundice?
- Increased levels of unconjugated bilirubin bc of low level of glucuronyltransferase (bc liver is not fully developed)
- Severe jaundice requires fluorescent light treatment
