Brs Biochem 08/23

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Set 08 Q: This enzyme produces an important oxidative metabolite through the conversion of L-arginine to citrulline; it is found in three isoforms in neuronal, macrophage, and endothelial tissues

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Nitric Oxide Synthase (NOS) - in macrophages NOS-2 (or iNOS) is important in killing phagocytosed bacteria. Endothelial NOS-3 stimulates the influx of Ca into vascular endothelial cells with activation of cGMP, resulting in relaxation of vascular smooth muscle. It is also known as endothelial-derived relaxation factor, or EDRF.

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Set 08 Q: This biotin requiring enzyme catalyzes the conversion of pyruvate to oxaloacetate, a key anaplerotic reaction of the tricarboxylic acid cycle

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Pyruvate Carboxylase - deficiency of this enzyme presents early with elevated levels of lactic acid in the blood because the conversion of pyruvate to oxaloacetate is blocked. Patients develop hypotonia, ataxia, and seizures.

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Set 08 Q: This genetic disorder results from the deficiency of hexosaminidase A, with accumulation of Gm2 gangliosides within neurons

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Tay Sachs disease - autosomal recessive, occurs primarily in Ashkenazi Jews, is marked by the presence of a distinctive cherry-red spot on the macula. Death occurs by age 4 due to mental and motor deterioration with blindness

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Set 08 Q: This, the most common lysosomal storage disease, results from the deficiency of glucocerebrosidase, with accumulation of glucocerebrosides in macrophages

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Gaucher disease - autosomal recessive, accumulation in macrophages result in a wrinkled tissue paper cytoplasm and lead to hepatomegaly, erosion of the femoral head and a mild anemia

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Set 08 Q: This disorder results from the x-linked deficiency of alpha-galactosidase A, with accumulation of ceramide trihexoside

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Fabry's disease - deficiency of this lysosomal enzyme results in angiokeratomas (painful skin lesions), with death due to renal failure from ceramide thrihexoside accumulation in early adulthood. Also see burning neuropathy in hands/feet

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Set 08 Q: A disorder that results from the deficiency of the lysosomal enzyme sphingomyelinase, with accumulation of sphingomyelin within phagocytes

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Niemann-Pick disease - autosomal recessive. Marked histologically by the presence of "foamy histiocytes," results in progressive hepatosplenomegaly and neurologic deterioration with death by age 3.

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Set 08 Q: This condition results from the autosomal recessive deficiency of galactocerebroside B-galactosidase and the accumulation of galactosylsphingosine (galactocerebroside)

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Krabbe disease - this leukodystrophy results from the accumulation of a molecule toxic to oligodendrocytes. Clinical consequences of demyelination include peripheral neuropathy, developmental delay, optic atrophy, spasticity and rapid neurodegeneration, leading to death

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Set 08 Q: An autosomal recessive disorder resulting from a deficiency of arylsulfatase, with the accumulation of sulfate-containing lipids within neurons.

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Metachromic Leukodystrophy - causes the demyelination of neurons and accumulation of sulfatides in macrophages, resulting in metachromatic shift of dyes used to stain histologic sections of tissues. Patients eventually develop loss of cognitive function and ataxia, hyporeflexia, and seizures - Will see a young patient presenting with inability to walk straight and losing previously acquired motor developmental milestones

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Set 08 Q: This fatal disorder results from a defect in the import of enzymes into the peroxisomes; the failure to produce such organelles leads to the accumulation of very long chain fatty acids and impaired production of bile acid

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Zellweger Syndrome - neurologic impairment results in death within the first year of age, with defects in the degradation of very long chain fatty acid and the formation of bile acid, which both take place partially within peroxisomes

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Set 08 Q: Genetic defects in this enzyme lead to an inability to use long-chain fatty acids as fuel in skeletal muscle, wtih resultant myoglobinemia and weakness following exercise.

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Carnitine Acetyltransferase deficiency - normally acyl groups from fatty acids are transported from the cytosol into the mitochondrial matrix via the carnitine shutle. Carnitine acetyltransferase I catalyzes the transfer of the acetyl moiety through a carrier attached to carnitine, where it is transferred back to CoA by carnitine acetyltransferase in the matrix.