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.
What are the characteristics of cholesterol structure?
4 ring structure
8-10 C side cahin at C17
OH at C3
double bond at C5 and C6
Where does cholesterol synthesis take place?
liver ER
what are the five molecules of cholesterol synthesis?
acetate to mavalonate to activated isoprene to squalene to cholesterol
What is the committment step of cholesterol synthesis? What enzymes are involved in this step?
acetate to mevalonate. HMG CoA synthase used (not the same enzyme as in ketone synthesis)
HMG CoA reductase is what is used to regulate cholesterol synthesis
What happens during the second step of cholesterol synthesis?
3 ATP are consumed in the conversion of mevalonate to activated isoprenes
What are important aspects of the conversion from activated isoprenes to squalenes (intermediates, things you have to put in)
polymerization phase
needs NADPH
intermediates are geranyl phosphate and farnesyl pyrophosphate
What is used up in the conversion of squalene to cholesterol?
NADPH
what to steps of cholesterol synthesis require energy?
mevalonate to activated isoprene: ATP
isoprene to squalene and squalene to cholesterol: NADPH
ACAT
esterifies cholesterol
where in the liver are bile acids made?
peroxisomes
7-alpha-hydroxylase
enzyme of bile acid synthesis
what three molecules are important for bile acid synthesis?
7-alpha-hydroxylase, oxygen, and NADPH
Describe how phosphorylation relates to HMG-CoA reductase activity
active when dephosphorylated
inactive when phosphorylated
AMPK (AMP dependent kinase) inactivates HMG-CoA reductase (not enough energy in cell!)
phosphoprotein phosphatase activates
Describe the SREBP/SCAP system
In ER, SREBP is bound to SCAP. it stays there, bound, as long as cholesterol is high
when cholesterol is low, SREBP/SCAP migrates to the golgi via vesicular transport
it is cleaved
a fragment of SREBP activates HMG CoA reductase gene
What do statins do?
HMG coA reductase competitive inhibitors
What does ezetimibe do?
blocks lumenal cholesterol uptake
Lesch NAhn
prob with HGPT during salvage. leads to too much uric acid. treat with allopurinol to inhibit xanthine oxidase
tyrosemia type II
problem with tyrosine aminotransferase
leads to excess tyrosine: ulcers
alkaptonuria
homogentisic acid oxidase deficiency
dark skin pigmentation, arthritis, dark urine. adult onset
tyrosinemia type I
fumarylacetoacetate hydroxylase deficiency
leads to toxic build up
liver failure, hepatitis, renal tubule failure, cabbage smell
oculocutaneous albinisim type I
tyrosinase deficiency. converst tyrosine to DOPA and DOPAquinione for melanin
visual loss, nystagmus
above what level is the friedewald equation invalid?
above 400 ml/dl
what enzymes and factors are needed in phe metab?
PAH. PAH also requires BH4, which is a gene product of DHPR.
niacin
increases hdl-c; reduces ldl-c. independent of this, it is needed for NAD and NADP synthesis
positive vs negative nitrogen balance
positive: proteins incorporated into body
negative: not enough proteins in diet or increased loss of proteins due to break down
