Unit 4 Small Group Session Flashcards
Problem 1: Carnitine deficiency Problem 2: HLD Type II (34 cards)
What are the 2 forms of systemic carnitine deficiency?
- Deficiency of carnitine transporter
2. Deficiency of CPT
What is the primary form of carnitine deficiency?
Deficiency of the transporter
How can you tell someone doesn’t have the transporter deficiency?
If liver and other tissues are also affected, then it’s unlikely to be a deficiency of the transporter as the liver has one transporter type and other tissues have another transporter type
How does primary carnitine deficiency impact plasma and tissue carnitine levels
Decreases both (kidneys can’t reabsorb carnitine into plasma due to transporter defect)
How do you treat primary carnitine deficiency?
Diet high in carnitine - high levels “push” the transporter
What is secondary carnitine deficiency?
A deficiency in either CPT II (mostly) or in CPT1 (rare and lethal)
What is the impact of secondary carnitine deficiency on fatty acids
Causes defective beta oxidation of fatty acids
How is the carnitine pool depleted in secondary carnitine deficiency
Acyl-carnitines accumulate and are excreted in the urine
What is the impact of acyl carnitines on free carnitine uptake?
Inhibitory
What are some symptoms associated with secondary carnitine deficiency (CPTII, severe form)
hypoketotic hypoglycemia, hyperammonemia, cardiac malfunction, and sometimes death
What are some symptoms associated with secondary carnitine deficiency (CPT II, mild form)
Muscle weakness during prolonged exercise, myoglobinuia (due to breakdown of muscle tissue)
How can you precipitate symptoms of the severe form of CPT II deficiency?
Periods of fasting
How do you treat secondary carnitine deficiency
Low fat diet, high carbohydrate diet, avoid fasting, supplement with medium chain FAs
Why is there general weakness and muscle tone in carnitine deficiency?
Due to insufficient substrates for energy metabolism
Why is there fasting hypoglycemia in carnitine deficiency?
impaired long chain FA metabolism means you can’t use FA for energy and need to use the glucose
What happens to glycogen stores during fasting in carnitine deficiency?
Depleted quickly
Why can’t people who have carnitine deficiency do effective gluconeogenesis during a fast?
Gluconeogenesis requires ATP, most of which comes from B-oxidation of FA, which can’t be performed without carnitine
Tissues that would use FA end up using _______
glucose
Why is there elevated FA in blood in carnitine deficiency?
decreased glucose levels lead to increased epinephrine, and epinephrine mobilizes TAGs of adipose tissue which
Why is there an absence of ketoacids following fasting in carnitine deficiency?
ketone synthesis requires acetyl CoA
Why is there an accumulation of tissue and plasma TAGs in carnitine deficiency?
Fatty acid excess is diverted and fed into other pathways like TAG synthesis
Why is there hyperammonemia in carnitine deficiency?
Ureagenesis requires ATP, which comes primarily from B-oxidation
What are the two defects that can cause HLD Type IIA
- LDL receptor defect
2. Defect in the ligand-binding region of Apo-B-100
Statins inhibit what enzyme?
HMG-CoA Reductase
