Chapter 16 ( Lipid Mobilization And Catabolism ) Flashcards
Mechanism of Niacin in ttt of hyperlipidemia ?
Inhibit HSL in adipose tissue , with fewer fatty acids entering the liver , both VLDL and its product LDL will be lower in serum
What is the main enzyme responsible for fatty acid entry into mitochondria ? Its control ?
Carnitine acyltransferase-1
Inhibited by Malony-CoA
Insulin indirectly inhibit Beta oxidation by ativating acetyl-CoA carboxylase and increasing the malonyl-CoA concentration in the cytoplasm
Glucagon reverse this process
MCAD deficiency ? Features ? Ttt ? Prevention ?
Autosomal Recessive with variable expression Features : Fasting hypoglycemia Low or absent ketones Lethargy , coma , death Diagnosis : Dicarboxylic acidemia Dicarboxylic aciduria C8-C10 acyl canitines in blood Ttt : IV glucose Prevention : frequent feeding , high carbohydrate , low fat diet
Myopathic CAT/CPT deficiency ? Features ?
Autosomal Recessive with late onset
Features :
Muscle aches , weakness
Myoglobinuria
Provoked by prolonged exercise especially after fasting, cold or associated stress
Diagnosis :
Muscle biopsy shows elevated muscle triglycerides detected as lipid droplets in the cytoplasm
Ttt : cease muscle activity and give glucose
How to differentiated myopathic CAT deficiency from McArdle disease ?
Myopathic CAT deficiency : oil red O stain positive or Sudan black positive under microscope
McArdle disease : PAS positive material under microscope
Ackee fruit in Jamaica mechanism and features ?
Mechanism : contain toxin called Hypoglycin that acts as inhibitor of fatty acyl-CoA dehydrogenase
Features : jamaican vomiting and sever hypoglycemia of sudden onset followed by convulsions , coma , death
The 2 important enzymes in Propionic acid pathway ?
1- Propionyl-CoA carboxylase ( ATP, Biotin , CO2 )
2- Methymalonyl-CoA mutase ( vit B12 )
How to differentiate between Vit B12 and folate deficiency ?
In Vit B12 there is Methylmalonic aciduria
How acetoacetate is activated in extrahepatic sites ( muscle , renal cortex , brain ) ?
Thiopharase converts it to Acetoacetyl-CoA
Major enzymes of Ketogenesis ?
HMG-CoA synthase
HMG-CoA lyase
Why can’t liver metabolizes ketone bodies ?
Because it lacks Thiophorase ( acetoacetyl-CoA transferase )
Why urinary nitroprusside test can dramatically underestimate ketoacidosis and its resolution during ttt ?
As it detects only acetoacetate and doesn’t detect Beta-hydroxybutyrate , and in diabetics and alcoholics the ratio between them shifts and Beta-hydroxybutyrate predominates
Tay-Sachs defect ? Accumulating substrate ? Symptoms ?
Defect : Hexosaminidase A deficiency Substate accumulating in inclusion body : Ganglioside GM2 Symptoms : Cherry red spots in macula Psychomotor retardation Blindness Startle reflex Death < 2 years
Gaucher disease defect ? Substrate accumulating ? Symptoms ?
Defect : Glucocerebrosidase deficiency Substrate accumulating : glucocerebroside Symptoms : Crumble paper inclusions Hepatosplenomegaly Erosions of bones and fractures Pancytopenia or thrombocytopenia
Niemann-Pick disease defect ? Substrate accumulating ? Symptoms ?
Defect : Sphingomyelinase Substrate accumulating : Sphingomyelin Symptoms : cherry red spot in macula Foamy macrophages with zebra bodies Hepatosplenomegaly Microcephaly , mental retardation Early death
Fabry disease defect ? Accumulating substrate ? Symptoms ?
Defect : alpha-galactosidase deficiency
Accumulating substrate : Ceramide trihexoside
Symptoms : burning sensation in hands that get worse with exercise and hot weather
Angiokeratomas
Corneal cloudiness
Increased risk of heart attack or stroke
Heart and kidney enlargement
Renal failure the commonest cause of death
