SYSTEMIC CARNITINE DEFICIENCY Flashcards
naturally occuring amino acid derivative, produced by kidneys and liver
systemic carnitine deficiency
carnitine is synthesized endogenously from essential amino acid ______ with terminal groups donated by _____ (SAM)
lysine and s-adenosylmethionine
systemic carnitine deficiency is a _____ disorder that prevents the body from utilizing fats for energy
autosomal recessive disorder
3 areas of involvement include:
the _______ which is affected by progressive cardiomyopathy
cardiac muscle
3 areas of involvement include:
the _______ which is affected by encephalopathy caused by hypoketotic hypoglycemia
central nervous system
3 areas of involvement include
the __________- which is effected by myopathy
skeletal muscle
autosomal recessive disorder wherein both parents should have defect in SLC22A5 gene which is responsible for carnitine production and OCTN2 mutations impair transporters to plasma membrane
primary SCD
secondary to metabolic disorder
secondary SCD
affects only the liver resulting in reduced fatty acid oxidation and lipid accumulation and ketogenesis with hypoglycemia
inherited CPT-2 deficiency
primary SCD
autosomal recessive disorder wherein both parents should have defect in _______ gene which is responsible for carnitine production and _______ mutations impair transporters to plasma membrane
SLC22A5 gene
OCTN2 mutations
_____________ - consequence of impaired fatty acid oxidation and lipid accumulation with muscular weakness
hypoglycemia
mutations in the ______ gene cause systemic carnitine deficiency
SLC22A5 gene
The SLC22A5 gene provides instructions for making protein called _____ that transports carnitine cells
OCTN2
________ serves as a carrier of long chain fatty acids across the mitochondrial membrane
carnitine
in the cytosol FFA are activated by esterification to CoAsh by ______________ synthetase
acyl coa synthetase
Net _____ ATP equivalents is consumed to activate 1 FFA to a thioester
2 ATP
formation of _________ through the enzyme CPT1
acylcarnitine
formation of acylcarnitine through the enzyme ____________
Carnitine palmitoyl transferase-1
Formation of Acylcarnitine through the enzyme CPT1
Acylcarnitine will now be transferred to the matrix in exchange for another free carnitine through ______________
carnitine acylcarnitine translocase
carnitine and fatty acyl CoA liberation
one acylcarnitine is inside the mitochondrial matrix _______ will break down acylcarnitine into carnitine and fatty acyl CoA
CPT2
most peripheral tissues which normally use fatty acids, become glucose dependent
increased _________
gluconeogenesis
enzymes located at the outer mitochondrial membrane
acyl-coA synthetase
CPT-1
enzymes located at the inner mitochondrial membrane
carnitine acylcarnitine translocase
CPT-2
in the presence of ATP and coenzyme A, the enzyme ___________- catalyzes the conversion of a fatty acid to an “active fatty acid” or acyl-CoA using one high energy phosphate and forming AMP and PP1
acyl-coA synthetase (thiokinase)
in the presence of ATP and coenzyme A, the enzyme acyl coA synthetase (thiokinase) catalyzes the conversion of a fatty acid to an “active fatty acid” or acyl-CoA using one high energy ___________ and forming AMP and PP1
high energy phosphate
in the presence of carnitine however ____________, located in the outer mitochondrial membrane, transfers the long chain acyl group from CoA to carnitine, forming acylcarnitine and releasing CoA.
Carnitine palmitoyltransferase-I
in the presence of carnitine however carnitine palmitoyltransferase-I, located in the outer mitochondrial membrane, transfers the long chain acyl group from CoA to carnitine, forming ____________________.
acylcarnitine and releasing CoA
acylcarnitine is able to penetrate the inner membrane and gain access to the beta oxidation system of enzymes via the inner membrane exchange transporter ____________
carnitine acylcarnitine translocase
the acylgroup is then transfered to CoA so that acyl-CoA is reformed and carnitine is liberated. This reaction is catalyzed by ___________
carnitine palmitoyl transferase II
carnitine palmitoyl transferase II is located on the inside of the _________-
inner mitochondrial membrane
inherited _________ affects only the Liver, resulting in reduced fatty acid oxyidation and ketogenesis, with hypoglycemia
CPTI- deficiency
____________ deficiency affects primarily the skeletal muscle and when severe the liver.
CPTII deficiency
the ___________ drugs (glyburide, glibenclamide and tolbutamide), used in the treatment of type 2 diabetes mellitus, reduce fatty acid oxidation and therefore hyperglycemia by inhibiting CPT-1
sulfonylurea drugs
