Lipid disorders, fatty acid metabolism, and ketones

Question 1

type 1 hyperchylomicronemia: increased blood levels, deficits, inheritance

Answer 1

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.

Question 2

clinical manifestations of type 1 hyperchylomicronemia

Answer 2

pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas. no incr. risk for atherosclerosis.

Question 3

familial hypercholesterolemia: lab findings, inheritance, defect

Answer 3

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.

Question 4

familial hypercholesterolemia presentation

Answer 4

accelerated atherosclerosis (MI before age 20, tendon xanthomas, and corneal arcus (circle on the outside of the iris).

Question 5

hyptertriglyceridemia

Answer 5

incr. levels of VLDL and TGs. autosomal dominant d/t overproduction of VLDL. causes pancreatitis.

Question 6

carnitine deficiency

Answer 6

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

Question 7

Acyl CoA dehydrogenase deficiency

Answer 7

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.

Question 8

ketones

Answer 8

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

Question 9

hallmarks of fatty acid oxidation metabolism disorders

Answer 9

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.

Question 10

What happens wrt ketones in prolonged starvation/diabetic ketoacidosis?

Answer 10

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.

Question 11

rate limiting enzyme in ketogenesis

Answer 11

HMG-CoA syntheatase

Question 12

rate limiting enzyme in cholesterol synthesis

Answer 12

HMC CoA reductase