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A 25-year-old woman stops going to her aerobic exercise class because of severe muscle cramps that have occurred during every session for the past 2 months. Four hours after each session, she notices that her urine is a brown/red color. On physical examination, she has normal muscle development and strength. An inherited defect in which of the following substances is most likely to explain her findings?*Is she likely to have cardiac complications?
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*McArdle disease-Type 5 glycogen storage disease involves autosomal recessive defect in MUSCLE GLYCOGEN PHOSPHORYLASE, can't phosphorylate>Accumulation of glycogen in muscle>Painful muscle cramps with Myoglobinuria(Marks rhabdomyolosis).*FA says that ELECTROLYTE ABNORMALITIES(Due to muscle fiber break down and release of electrolytes) can result in ARRHYTHMIA in patients with Mcardle's disease.
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A 6-month-old male infant has failure to thrive andabdominal enlargement. His parents are concerned that he has shown minimal movement since birth. On physical examination, the infant has marked muscle weakness and hepatosplenomegaly. A chest radiograph shows marked cardiomegaly. He dies of congestive heart failure at age 19 months. A deficiency of which of the following enzymes is most likely to be present in this infant?
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*This is autosomal recessive condition involving lysosomal glucosidase.*Particularly alpha 1,4 glucosidase with alpha1,6 glucosidase activity(Acid maltase).*Patients are at increased risk of RESTRICTIVE cardiomyopathy, Hypotonia,proximal muscle weakness with hepatosplenomegaly and macroglossia(large tongue) are other common findings.
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A 9-year-old boy is being evaluated for deafness. Physical examination reveals a child with short stature, coarse facial features =GARGOYLISM=(low, flat nose, thick lips, widely spaced teeth, facial fullness), a large tongue, and clear corneas. Laboratory examination reveals increased urinary levels of heparan sulfate and dermatan sulfate. Metachromatic granules (Reilly bodies-due to accumulation of GAG s) are found in leukocytes from a bone marrow biopsy and in Neurons we see Zebra bodies(accumulation of GAGs). These leukocytes are also found to be deficient in iduronosulfate sulfatase. What is the correct diagnosis?
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*Hunter's syndrome is X-linked recessive def. of Iduronate sulfatase>MPS withOUT corneal clouding(Contrast this with Hurler's where there is corneal clouding)
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*U just woke up and u are about to have first meal.*Till u do so which one is true?*Ketone bodies are produced by liver/Glucose is synthesized by Fatty acid.
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*Ketone body synthesis begins 90 Mins after meal, to maintain blood glucose. so first choice is correct(u haven't eaten whole night),however muscles and other tissue rapidly take up ketone bodies and they aren't measured well during first days, however they are MADE by liver even 90 mins after meal.*Glucose can NOT be synthesized by Fatty acids, But glucose can be used to synthesize Fatty acids.(remember FAG<Not trying to be rude, but i promise you won't mess these 2 up)
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*Some guy on forums said that san fillipo syndrome was on the exam
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*Here u lack eznyme that degrades heparan sulfate, patients have emotional instability,Mental retardation and love to eat stuff they shouldn't(pica)*it is autosomal reccessive,MPS3.Facial dysmorphism,hirsutism.
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*Enzyme which catalyzes esterification of 2/3 of plasma cholesterol(From Nascent HDL >Mature HDL) VS enzyme which mediates transfer of Cholseterol ESTERS to other lipoprotein particles(VLDL,IDL,LDL)?
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*LCAT(Lecithin–cholesterol acyltransferase) vs CETP(Cholesterol Ester Transfer Protein)They can describe experiment where Nacent HDL can't be transformed to Mature HDL and ask you defect in enzyme-lCAT.(remember I am Mature CAT)*They can also do the same with transfer of cholesterol esters from MATURE HDL to Other Lipoproteins(VLDL,IDL,LDL)-CETP.
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Does insulin induce Cholesterol synthesis?
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*Yes it can as Insulin Induces activity of HMG-CoA reductase(3-hydroxy-3-methyl-glutaryl-coenzyme A reductase)<remember this is the enzyme that is inhibited by STATINS(COMPETITIVE,Reversible inhibition-we increase Km-the amount of substrate to give us the same effect without altering maximal effect Vm, thus dose-response curve is shifted towards right)
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*19 year-old patient had MI.*He has Corneal arcus(white, grey, or blue opaque ring in the corneal margin) on physical examination.(What other sign would most likely be present and would be pathognomonic for this disease?)*Is he homozygote/heterozygote if his cholesterol is 444?*What is inheritance?*Defect?
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*Patient likely has type 2A Familial Hypercholesterolemia which is Autosomal DOMINANT condition that results from absent/defective LDL receptors.*Achilles Tendon xanthoma is pathognomonic finding on physical exam.(For familial Hypercholesterolemia-Type 2 dyslipdemia)*They have accelerated atherosclerosis and can develop MI before age of 20.(otherwise very unusual)*444 is more close to 300 than it is to 700 thus patient is most likely Heterozygote, homozygotes would have levels around 700.*Heterozygote form is wayy more common(1:500) but both have increased risk of MI before age of 20.*Elevated LDL is due to Lack of /defective LDL RECEPTORS, CHOLESTEROL synthesis increases because even though there is BUNCH of LDL out of cells, we can't uptake them inside, so HMG-Coa is not inhibited by negative feedback and Produces MORE cholesterol.<Know that...
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Pancreatic Lipase Vs Hepatic Lipase vs Hormone sensitive lipase vs LPL?
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*Pancreatic lipase degrades dietary TGs in small intestine.*Hepatic Lipase degrades TG that are left in IDL(Basically converts IDL to LDL)- remember Hepatic lipase and IDL by Hi :)*Hormone sensitive lipase(Downregulated by Insulin)degrades TGs in Adipocytes.*LPL(Expressed on Vascular Endothelial surface)-eats up and breaks down TG in Chylomicron(releasing FAs and leaving Chylomycron remnants) and in VLDL(release FAs and leaves IDL)-Thus lack of LPL or its cofactor C-II results in Hyperchylomicronemia(Type 1 dislipidemia-Autosomal Recessive), where u have elevated Chylomicrons,TG and Cholesterol, as LDL is not elevated patients don't have increased risk of atherosclerosis..(However they can have HEPATOSPLENOMEGALY,Pancreatitis,Pruritic(ITCHY)/Eruptive xanthomas with white creamy layer in supernatant contras tthis with Turbid INFRAnate after refrigenation in type IV-hypertriglycerimia(Increased VLDL is responsible for that finding.)
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*Are high levels HDL good?
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*Yes as it is protective for vascular health.*It is Happy or Healthy HDL :)*HDL originates from Intestines and Liver and it is "movable fist basically" that hands out cholesterol esters to other lipoproteins(after Nascent HDL>Mature HDL by LCAT), this movable fist also hands out ApoC2(LPL cofactor -to get chylomicron remnants by LPL) and and ApoE(needed for uptake of chylomicron remnants and other lipoproteins by Liver.).*Remember HILL(HDL from Intestine and Liver Liver :) but note that HDL is involved in REVERSE Cholesterol transport from periphery to liver and HDL is what removes Cholesterol from fatty streaks in atherosclerotic plaques, note that HDL synthesis is increased by alcohol.
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*You just ate lot's of Mcdonald's burgers(Lot's of Fatty acids,cholesterol-rich).
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*Cholesterol should be esterified by LCAT and then Cholesterol esters and Fatty acids can be up taken by chylomicrons which are secreted by enterocytes(Intestinal epithelial cells), Chylomicrons deliver TG to peripheral tissues + it delivers cholesterol to Liver indirectly (After being broken down into Chylomicron remnants by LPL in process of fatty acid release from these chylomicrons for peripheral tissues/Adipocytes, note that Chylomicrons deliver Cholesterol to liver while IDL delivers cholesterol but also trIglcyerides to liver, contrast this to chylomicron remnants which are depleted of TGs),remember Liver contains receptors for chylomicron remnants and LDL.
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*What are lipoproteins?
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*These are amphipathic(has both hydrophobic and hydropilic ends)molecules hat are composed of varying proportions of TGs,Cholesterols,phospholipids.*From low to high density:Chylomicrons<VLDL<LDL<HDL.*Generally,Higher density refers to MORE cholersterol, LESS TG and Smaller size.(Don't get fooled by" LOW" density lipoprotein name, it "Low density" is in reltive to HDL ,otherwise LDL is "More dense" then any other lipoproteins like VLDL and Chylomicrons and here comes important point LDL actually contains The Most amount of cholesterol, more than HDL, HDL has highest density due to its high Protein component ,once again LDL has More cholesterol while HDL has More protein)*Now HDL<LDL<VLDL<Chylomicrons in terms of Size and TG content(Hence you know why TG is increased in Type1(increased Chylomicrons) and in type 4(increased VLDL) dyslipidemias.*All these is meant to give you backrground don't try to memorize these(unless for med school tests) try to imagine,draw them out if you have time, it will make other HY stuff easy to understand and comprehend as we saw with dislipdemias.
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*Describe Key,HY points about chylomicrons.
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*Dietary(EXOgenous) lipids in enterocytes will combine with newly translated apolipoproteins(Like apo-B45) in ER.*Chylomicrons usually contain other apopliprotiens too like C2 and E.*Now,from intestine Chylomicrons enter lymphatics>Thoracic duct>Blood,in blood they deliver TGs to PERIPHERAL tissues as they are released by LPL, after whichwe are left with Chylomicron remnants which can enter Liver and give our liver some cholesterol.(But not much TGs at they have been stolen by peripheral tissues, contrast this with IDL-degradation product of VLDL which delivers TGs and cholesterol to liver)*Remeber Chylomicrons are secreted by intestinal epithelial cells.
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*Key,HY points about VLDL/IDL/LDL?Contrast VLDL with Chylomicron.
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*Well it VLDL is synthesized in liVer, its main function is to deliver hepatic/endogenous TGs to PERIPHERAL tissues(Consrast this with Chylomicrons which deliver EXOGENOUS=dietary TGs to PERIPHERAL tissue-so they have similar function), but note that VLDL contains more Cholesterol and delivers it to peripheral tissues too.*VLDL is smaller in size and has less TGs.*Also Chylomicron doesn NOT have ApoB100(it does express B45,A1,C2,E.) contrast this with VLDL which expresses ApoB100,C2,E2 but does NOT express ApoB48,A1(remember functions and it will make sense VLDL doesn't need ApoB48 which is needed for CHYLOMICRON secretion and it also doesn't need A1 which activates LCAT)*Now when LPL acts on VLDL, it eats up TGs and leaves IDL(IDL doesn't have C-II but keeps E and B100), as IDL is metabolized by Hepatic lipase we receive LDL(which looses E and keeps Only B100), now if u know this it is easy to answer the question: by which apolipoproteins LDL receptors recognize and promote receptor mediated endocytosis in peripheral tissue?(Obv only one that LDL has left is ApoB100)-Remember LDL should deliver cholesterol from liver to peripheral tissues.it suckss but apolipoproteins are testable, remember the sequence like it is story.. really know the red stuff...Also remember:*Decreased ApoproteinB synthesis in Kwashiorkor disease due to protein deficiency contributes to fatty liver.
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*Why VLDL and IDL can bind LDL receptors?
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*Because all 3 express ApoB100<function of which is Binding LDL receptors.*Note that IDL also expresses ApoE while VLDL also expresses C2.
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