Fats Flashcards
Niemann-Pick. A vs. B.
Enzyme: sphingomyelinase: converts ceramide-POPC into ceramide.
A. neonatal onset and neuro involvement. Death at 2-3
B: childhood onset and little neuro involvement death in late teens/early 20s.
Organs: liver, bone marrow, neural tissue
Foam cells
Faber disease
ceramidase (conversion of ceramide to spingosine and fatty acids)
painful joints, nodules near joints, hoarsness, neuro, cardiac, lung, lymph nde
failure to thrive, developmental delay, early death
Metachromatic leukodystrophy
arylsulfatase A deficiency
ataxia, gait disturbance, loss of speech, blindness, seizures, behavioral problems
accumulation of galactosylsulfatide in the CNS and while matter and peripheral nerves
late infantile/juvenile onset.
Krabbe’s disease
galactosylceramide beta galactosidase deficiency
CNS degradation, spastic quadriplegia, blindness, optic atrophy, deafness, defuse demyelination throughout white matter
multinucleated globoid cells
death by age 2
Guacher’s disease types I, II, III
beta glucosidase deficiency (cant get from clucocerebrosidase to ceramide)
Type I: spleen, thrombocytopenia, anemia, bone marrow pain, no neuro
ERT possible. Jews.
Type II: neuro involved. spleen. rapid progression and death
III: childhood onset and later death
Sandhoff:
hexoaminidase A and B deficiency
cerebral degeneration beginning at 6 months
blindness, cherry macula, hyperacusis, bone change, hepatomegaly
Fabry Disease
X-linked.
alpha-galactosidase
accumulation of glycosphingolipids with alphagalactosyl moities
skin leisons, fever, severe pain, nephropathy, vascular disease, corneal and lenticular opacity, death. ERT available
Generalized gangliosidosis/Gm1
Beta galactosidase
types I, II, III
cerebral degenerative, skeletal deformities, coarse features, spleen, liver, cherry red macula
Tay-Sachs
hexoaminidase A
infantile degeneration of the brain and retina, cherry red macula, hyperacusis, doll fase
death by age 2
Hurler
Iduronidase deficiency.
normal at birth
coarse facial features, corneal clouding, liver, spleen, short stature
megalencephaly, bone marrow probs, valvular stenosis, lung disease, congestive heart failure neuro degeneration, deat at age 6
Scheie
Like Hurler, but milder.
death in early adulthood
Sanfilippo
mucopolysacchariade disorder with intellectual disability and severe neurological problems
Morquio
sever skeletal involvement. neurological function is normal.
What is the process of atherosclerosis?
LDL migrates into the subendothelial space and interacts with proteoglycans of the intima. LDL undergoes glycosylation and oxidation, leading to the fragmentation of apoB100. Macrophages take up this deformed apoB100 and become foam cells.
Foam cells stimulate secretion of monocyte chemostatic protien 1 (MCP1) which attracts more monocytes. Monocytes become macrophages via M-CSF. Accumulation of LDL foam cells leads to fatty streaks, and eventually apoptosis and necrosis.
cell death leads to an inflammatory response and smooth muscle proliferation. this produces collagesn and distends into the sup-endothelial space. endothelaila cells overlying the fbrous cap are lost and the leison is thrombogenic. platelets are activated.
How does lp(a) influence atherosclerotic ristk?
increases LDL entry into the arterial wall
sitosterolemia
problem with ABCG5 and ABCG8 transporters. these transporters excrete cholesterol and plant sterols into the intestine. these pts have high cholesterol and high plant sterols
Abetalipoproteinemia
MTP defect.
MTP needed for apoB lipoproteins (transfers triglycerides and cholesterol to the chylomicrons and VLDL.
cholesterol is low but lipid soluble vitamins are deficient and fat absorption is problematic
chylomicronemia
LPL or apoCII disorder
can’t clear apoB lipoproteins.
TG and CM very high
pancreatitis and pancreatic cancer killers
Familial dysbetalipoproteinemia
apoE2 variant with low LRP affinity.
not enough uptake of CMs and IDLs
increased TGs
xanthomas, palmar striae, tendonous xanthomas, increased atherosclerotic risk
familial hypercholesterolemia
autosomal dominant with incomplete dominance
LDLR gene defect
apoB100 uptake is insufficient, so more LDL in the plasma
Recessive hypercholesterolemia
ARH mutation= adaptor needed for clathrin mediated endocytosis of LDL-LDLR complex: high LDL and atherosclertotic risk
familial hypoalphalipoproteinemia
low HDL and increased atherosclerotic risk
Tangiers disease
ABC-A1 gene: poor cholesterol efflux from periphery. increased atherosclerosis and accumulation of cholesterol ester in macrophages
hyperalphalipoproteinemia
CETP is deficient- very high HDL. probably good for you.
