Flashcards in Lipid disorders, fatty acid metabolism, and ketones Deck (12):
type 1 hyperchylomicronemia: increased blood levels, deficits, inheritance
see increased levels of chylomicrons, triglycerides, and cholesterol. autosomal recessive. lipoprotein lipase or apolipoprotein C-II (LPL cofactor) deficiency. therefore, the body can't degrade TGs circulating in chylomicrons.
clinical manifestations of type 1 hyperchylomicronemia
pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas. no incr. risk for atherosclerosis.
familial hypercholesterolemia: lab findings, inheritance, defect
increased blood titers of LDL and cholesterol. esp. high prevalence in Quebec. Autosomal dominant (or incomplete dominant) inheritance. D/t absence of LDL receptors. Heterozygotes have cholesterol about 300 mg/DL; homozygotes have cholesterol about 700 mg/dL.
familial hypercholesterolemia presentation
accelerated atherosclerosis (MI before age 20, tendon xanthomas, and corneal arcus (circle on the outside of the iris).
incr. levels of VLDL and TGs. autosomal dominant d/t overproduction of VLDL. causes pancreatitis.
carninite is needed for transport of long chain fatty acids into the mitochondria, where they can be metabolized. without this, there is toxic accumulation of very long chain fatty acids. See weakness, hypotonia, and hypoketoic hypoglycemia
Acyl CoA dehydrogenase deficiency
Long chain fatty acids are shuttled into mitochondria as acyl CoA. with deficiencies, you will see incr. dicarboxylic acids, decr. glucose and ketonees. since Acetyl CoA is a positive allosteric regulator of gluconeogenesis, decr. acetyl CoA will cause decr. fasting glucose.
acetoacetate, betahydroxybutyrate, and acetone. during starvation (or during pathologic states like DM), ketones are produced from acetyl CoA in the liver.
urine test for ketones can't detect beta-hydroxybuterate
hallmarks of fatty acid oxidation metabolism disorders
aketosis or hypoketosis during starvation or metabolic decompensation, in the presence of metabolic acidosis.
moms pregnant with fetuses with FAO disorders have higher risk of HELPP during pregantcy. valproic acid is contraindicated in pts with FAO disorders.
What happens wrt ketones in prolonged starvation/diabetic ketoacidosis?
oxaloacetate is depleted for gluconeogenesis. in alcoholism, excess NADH shunts oxaolacetate to malate. both cause a build-up of acetyl CoA, which shunts glucose and FFA toward production of keton bodies.
rate limiting enzyme in ketogenesis