Dai3-Heme

Question 1

What is Methylmalonic acidemia (aciduria) MMA?

Answer 1

• 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

Question 2

What is the importance of Folic acid deficiency?

Answer 2

-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

Question 3

What are the pathological consequences of folic acid deficiency?

Answer 3

• Altered appearance of blood cells
• Anemia
• Neurological symptoms: irritability, forgetfulness

Question 4

What are the causes of Vitamin B12

(cobalamin) deficiency ?

Answer 4

• 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

Question 5

What is Pernicious anemia?

Answer 5

• 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

Question 6

What are the Biochemical consequences of B12 deficiency ?

Answer 6

• 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

Question 7

What is heme and its functions?

Answer 7

- A porphyrin, constituent of hemoglobin, myoglobin, cytochromes, and catalase.    
Functions:
- binds oxygen (hemoglobin)
- electron carrier (cytochrome)
- part of active site (catalase)

Question 8

Where does heme biosynthesis occur?

Answer 8

• Mitochondria (1st step)
• Cytosol (formation of porphyrin)
• Mitochondria (formation of heme)

Question 9

What is AIP (Acute Intermittent Porphyria)?

Answer 9

• 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

Question 10

What is PCT (Porphyria Cutaneous Tarda)?

Answer 10

• 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)

Question 11

What are the main steps in heme degradation & excretion?

Answer 11

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)

Question 12

What is jaundice?

Answer 12

• 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)

Question 13

What is neonatal jaundice?

Answer 13

• Increased levels of unconjugated bilirubin bc of low level of glucuronyltransferase (bc liver is not fully developed)
• Severe jaundice requires fluorescent light treatment