Fats Flashcards

1
Q

Niemann-Pick. A vs. B.

A

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

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2
Q

Faber disease

A

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

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3
Q

Metachromatic leukodystrophy

A

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.

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4
Q

Krabbe’s disease

A

galactosylceramide beta galactosidase deficiency
CNS degradation, spastic quadriplegia, blindness, optic atrophy, deafness, defuse demyelination throughout white matter
multinucleated globoid cells
death by age 2

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5
Q

Guacher’s disease types I, II, III

A

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

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6
Q

Sandhoff:

A

hexoaminidase A and B deficiency
cerebral degeneration beginning at 6 months
blindness, cherry macula, hyperacusis, bone change, hepatomegaly

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7
Q

Fabry Disease

A

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

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8
Q

Generalized gangliosidosis/Gm1

A

Beta galactosidase
types I, II, III
cerebral degenerative, skeletal deformities, coarse features, spleen, liver, cherry red macula

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9
Q

Tay-Sachs

A

hexoaminidase A
infantile degeneration of the brain and retina, cherry red macula, hyperacusis, doll fase
death by age 2

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10
Q

Hurler

A

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

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11
Q

Scheie

A

Like Hurler, but milder.

death in early adulthood

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12
Q

Sanfilippo

A

mucopolysacchariade disorder with intellectual disability and severe neurological problems

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13
Q

Morquio

A

sever skeletal involvement. neurological function is normal.

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14
Q

What is the process of atherosclerosis?

A

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.

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15
Q

How does lp(a) influence atherosclerotic ristk?

A

increases LDL entry into the arterial wall

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16
Q

sitosterolemia

A

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

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17
Q

Abetalipoproteinemia

A

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

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18
Q

chylomicronemia

A

LPL or apoCII disorder
can’t clear apoB lipoproteins.
TG and CM very high
pancreatitis and pancreatic cancer killers

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19
Q

Familial dysbetalipoproteinemia

A

apoE2 variant with low LRP affinity.
not enough uptake of CMs and IDLs
increased TGs
xanthomas, palmar striae, tendonous xanthomas, increased atherosclerotic risk

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20
Q

familial hypercholesterolemia

A

autosomal dominant with incomplete dominance
LDLR gene defect
apoB100 uptake is insufficient, so more LDL in the plasma

21
Q

Recessive hypercholesterolemia

A

ARH mutation= adaptor needed for clathrin mediated endocytosis of LDL-LDLR complex: high LDL and atherosclertotic risk

22
Q

familial hypoalphalipoproteinemia

A

low HDL and increased atherosclerotic risk

23
Q

Tangiers disease

A

ABC-A1 gene: poor cholesterol efflux from periphery. increased atherosclerosis and accumulation of cholesterol ester in macrophages

24
Q

hyperalphalipoproteinemia

A

CETP is deficient- very high HDL. probably good for you.

25
Q

What are the characteristics of cholesterol structure?

A

4 ring structure
8-10 C side cahin at C17
OH at C3
double bond at C5 and C6

26
Q

Where does cholesterol synthesis take place?

A

liver ER

27
Q

what are the five molecules of cholesterol synthesis?

A

acetate to mavalonate to activated isoprene to squalene to cholesterol

28
Q

What is the committment step of cholesterol synthesis? What enzymes are involved in this step?

A

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

29
Q

What happens during the second step of cholesterol synthesis?

A

3 ATP are consumed in the conversion of mevalonate to activated isoprenes

30
Q

What are important aspects of the conversion from activated isoprenes to squalenes (intermediates, things you have to put in)

A

polymerization phase
needs NADPH
intermediates are geranyl phosphate and farnesyl pyrophosphate

31
Q

What is used up in the conversion of squalene to cholesterol?

A

NADPH

32
Q

what to steps of cholesterol synthesis require energy?

A

mevalonate to activated isoprene: ATP

isoprene to squalene and squalene to cholesterol: NADPH

33
Q

ACAT

A

esterifies cholesterol

34
Q

where in the liver are bile acids made?

A

peroxisomes

35
Q

7-alpha-hydroxylase

A

enzyme of bile acid synthesis

36
Q

what three molecules are important for bile acid synthesis?

A

7-alpha-hydroxylase, oxygen, and NADPH

37
Q

Describe how phosphorylation relates to HMG-CoA reductase activity

A

active when dephosphorylated
inactive when phosphorylated
AMPK (AMP dependent kinase) inactivates HMG-CoA reductase (not enough energy in cell!)
phosphoprotein phosphatase activates

38
Q

Describe the SREBP/SCAP system

A

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

39
Q

What do statins do?

A

HMG coA reductase competitive inhibitors

40
Q

What does ezetimibe do?

A

blocks lumenal cholesterol uptake

41
Q

Lesch NAhn

A

prob with HGPT during salvage. leads to too much uric acid. treat with allopurinol to inhibit xanthine oxidase

42
Q

tyrosemia type II

A

problem with tyrosine aminotransferase

leads to excess tyrosine: ulcers

43
Q

alkaptonuria

A

homogentisic acid oxidase deficiency

dark skin pigmentation, arthritis, dark urine. adult onset

44
Q

tyrosinemia type I

A

fumarylacetoacetate hydroxylase deficiency
leads to toxic build up
liver failure, hepatitis, renal tubule failure, cabbage smell

45
Q

oculocutaneous albinisim type I

A

tyrosinase deficiency. converst tyrosine to DOPA and DOPAquinione for melanin
visual loss, nystagmus

46
Q

above what level is the friedewald equation invalid?

A

above 400 ml/dl

46
Q

what enzymes and factors are needed in phe metab?

A

PAH. PAH also requires BH4, which is a gene product of DHPR.

47
Q

niacin

A

increases hdl-c; reduces ldl-c. independent of this, it is needed for NAD and NADP synthesis

48
Q

positive vs negative nitrogen balance

A

positive: proteins incorporated into body
negative: not enough proteins in diet or increased loss of proteins due to break down