1231

Question 1

Galactose metabolism?

Answer 1

Most commonly from lactose (glucose-galactose), with lactase in GI breaking down. Galactose -(galactokinase)-> galactose-1P -(Uridyltransferase)-> Glucose-1-P

Question 2

Galactokinase deficiency?

Answer 2

AR. Galactose in blood and urine. Galactitol accumulation (via aldose reductase) -> infantile cataracts (failure to track or develop social smile).

Question 3

Classic galactosemia

Answer 3

AR. Absence of galactose-1-phosphate uridyltransferase. Galactitol accumulation (via aldose reductase) -> cataracts. FTT, jaundice, hepatomegaly, ID. Tx = exclude galactose and lactose.

Question 4

Sorbitol

Answer 4

Keeping glucose in a cell for later use into fructose via sorbitol dehydrogenase. (Glucose -aldose reductase-> sorbitol). Liver, ovaries, seminal vesicles have both. Schwann cells, retina, kidneys, lens primarily has aldose reductase, making these cells susceptible to osmotic dmg with hyperglycemia OR with high galactose lvls.

Question 5

Lactase deficiency

Answer 5

Primary - age-dependent decline (absence of lactase-persistent allele)Secondary - loss of BRUSH BORDERDx - stool w/ dec. pH and breath with inc. hydrogen content with lactose tolerance test.Osmotic diarrhea.

Question 6

What aa’s found in histones?

Answer 6

Positively charged (basic) Arginine and lysine.

Question 7

Glucogenic aa’s v. Ketogenic aa’s?

Answer 7

Met, Val, His v. Leu, Lys; Ile, Phe, Thr, Trp are both.VeHeMetly sugary. Kato went to LaLa land.PITT - best of both worlds.

Question 8

Rate limiting enzyme of urea cycle?

Answer 8

Carbomyl phosphate synthetase I. In mitochondria. CO2 + NH3 + 2ATP -> Carbomyl phosphate

Question 9

Urea Cycle?

Answer 9

Carbomyl phosphate + ornithine -(ornithine transcarbamylase)-> citrulline + Asp + ATP -(argininosuccinate synthetase)-> argininosuccinate -(argininosuccinase)-> arginine + (fumarate) -(Arginase)-> Urea + ornithinePoint is to remove ammonia. (Urea gets N from ammonia and aspartate).

Question 10

How does ammonia from muscle get to the liver?

Answer 10

Turned into alanine before transported to liver for transamination into pyruvate + glutamate (->-> urea)

Question 11

AST and ALT do what?

Answer 11

Asparate + alpha-ketoglutarate oxaloacetate + glutamate

Alanine + alpha-ketoglutarate pyruvate + glutamate

Question 12

Hyperammonemia

Answer 12

Acquired (liver disease) or secondary (urea cycle pblem) - excess free NH4, depleting alpha-ketoglutarate, which stops TCA. Tx = limit protein. Benzoate or phenylbutyrate, which bind aa to excrete. Lactulose to acidify GI and trap NH4+ for excretion. Asterixis, slurring, somnolence.

Question 13

Hereditary hyperammonemias

Answer 13

Ornithine transcarbamylase deficiency - X-linked rec. Mitochondria. Excess carbonyl phosphate -> orotic acid. Inc. orotic acid, dec. BUN, hyperammonemia symptoms. NO megaloblastic anemia unlike orotic acuduria.CPS-1 deficiency

Question 14

Phenylalanine, Tryptophan, and Histidine make what important compounds?

Answer 14

Phe - Thyroxine, Melanin, Dopamine, NE, EpiTry - Niacin, NAD, Serotonin, MelatoninHis - Histamine

Question 15

Glycine, Glutamate, Arginine make what important compounds?

Answer 15

Gly - Porphyrin, hemeGlut - GABA, glutathioneArginine - Creatine, Urea, Nitric oxide

Question 16

Overview of Phenylalanine/Tyrosine catabolism?

Answer 16

Phe -(phenylalanine hydroxylase, BH4)-> Tyr; PKUTyr -(tyr hydroxylase,BH4)-> DOPA -(DOPA decarboxylase, B6)-> dopamine-(r. VitC)-> NE -(r. SAM)-> Epi -> MetanephrineDopamine -> homovanillic acidNE -> Normetanephrine -> vanillylmandelic acidDOPA -(tyrosinase)-> melanine; ALBINISMTyr ->-> homogentisic acid -(Homogentisate oxidase)-> Maleylacetoacetic acid -> TCA; Alkaptonuria

Question 17

Alkaptonuria

Answer 17

AR. Benign. Deficiency of homogentisate oxidase (tyr -> fumarate pathway). Dark CT, brown sclerae, urine turns black in air. Arthralgias (2/2 cartilage tox of homogentisic acid)

Question 18

Homocystinuria

Answer 18

Homocystein in urine, ID, osteo, tall, kyphosis, lens, atherosclerosis.Varied etio - Cystathionine synthase deficiency, homocysteine methyltransferase deficiency, dec. pyridoxal phosphate binding to cystationine synthase

Question 19

Cystinuria

Answer 19

Defect of aa transport (COLA) in renal proximal convoluted tubule leading to hexagonal cystine (=cysteine x2) stones. AR. Dx = cyanide-nitroprusside test. Tx = urinary alkalinization and chelating.

Question 20

Maple Syrup Disease

Answer 20

Normally branched chained aa’s (Ile, Leu, Val) converted to alpha-keto acids peripherally via alpha-ketoacid dehydrogenase (B1). Urine smells like syrup. FTT, CNS defects, ID.Tx = restrict ILV (I Love Vermont), and thiamine +keto acid supplementation

Question 21

Glycogen regulation by insulin and glucagon/epi?

Answer 21

Glucagon and epi both eventually act on glycogen phosphorylase kinase, which phosphorylates glycogen phosphorylase. Glucagon (liver) and Epi-Beta (liver and muscle) -> adenylate cyclase pathway and PKA. Epi-alpha (liver) uses ER and Ca2+ directly onto glycogen phosphorylase kinase.Insulin inhibits glycogen phosphorylase via a phosphatase. And pushes glycogen synthase.

Question 22

Glycogenolysis?

Answer 22

Glycogen phosphorylase removes branch down to 4 residues. 4-alpha-D-glucoanotransferase moves 3 glucose-1P’s, then alpha-1,5 glucosidase cleaves last oneCleaves off glucose-1P -(glucose-6-phosphatase)-> Glucose-6-P

Question 23

Glycogenesis?

Answer 23

Glucose 1-P -(UDP-glucose pyrophosphorylase)-> UDP-glucose -(glycogen synthase)-> glycogen;Links are alpha-1,4 while branches are alpha-1,6

Question 24

Glycogen storage disease (four of them)

Answer 24

Very Poor Carbohydrate MetabolismVon Gierke (most common), Pompe, Cori, McArdle (V)

Question 25

Von Gierke disease (type I)

Answer 25

Glucose-6-phosphatase; Severe fasting hypoglycemia. Lactate high, glycogen high, hepatomegaly. Cells can't remove phosphate off of glucose-6P; AR. Tx = freq. oral glucose; avoid fructose and galactose.

Question 26

Pompe disease (II)

Answer 26

Lysosomal alpha-1,4-glucosidase (small amount of glycogen degraded via this method). Cardiomyopathy. AR. So much POMPE for little lysosomal enzyme.

Question 27

Cori disease (III)

Answer 27

Alpha-1,6,glucosidase (last debranch). AR. Gluconeogenesis okay. Mild von Vierke.

Question 28

McArdle disease (IV)

Answer 28

Skeletal muscle glycogen phosphorylase. AR. Increased Glycogen in MUSCLE but CAN'T break down-> cramps, MYOglobinuria with exercise, arrhythmias.

Question 29

Fabry Disease

Answer 29

alpha-galactosidase A. Ceramide trihexoside. XR. Peripheral neuropathy, angiokeratomas, cardio/renal. Fabry

Question 30

Gaucher disease

Answer 30

Glucocerebrosidase (B-glucosidase). Glucocerebroside. AR. Hepatosplenomegaly, pancytopenia, GAUCHER cells (lipid-laden macrophages!). Recombinant glucocerebrosidase available tx. Gaucher cells love fat, but Gaucher loves glucose.

Question 31

Tay-Sachs disease

Answer 31

Hexosaminidase A. GM2 ganglioside. AR. CHERRY-Red spot on macula. No hepatosplenomegaly. A HEX on the people.

Question 32

Krabbe disease

Answer 32

Galactocerebrosidase. Krabby Krabbe left with leftover sugar (Galactose). AR. Peripheral neuropathy, dvpt delay.

Question 33

Metachromatic leukodystrophy

Answer 33

Arylsulfatase. Central and peropheral demyelination with ataxia, dementia.

Question 34

Hurler syndrome

Answer 34

alpha-L-iduronidase. AR. Heparan sulfate. Dvpt delay, gargoylism, airway, corneal.

Question 35

Hunter syndrome

Answer 35

iduronate sulfatase. Mild hurler + aggressive.

Question 36

Carinitine deficiency?

Answer 36

Carnitine shuttle is required to move LCFA's into mitochondria to be broken down. W/o carnitine, accumulated LCFA's --> cardiomyopathy, myopathy, encephelopathy, fasting hypoglycemiaPrimary - carnitine palmitoyltransferases I or IICPT-I is inhibited by malonyl-CoA

Question 37

Ketogenesis

Answer 37

Only occurs in mitochondria of liver cells with lots of acetyl-CoA present. Acetoacetate and 3-hydroxybutyrate can be used peripherally. Acetone, cannot, and leaves via lungs (fruity odor)

Question 38

Kcal per protein, carb, fat?

Answer 38

4,4,9.

Question 39

How much time does it take to deplete glycogen?

Answer 39

1 day

Question 40

Starvation days 1-3:

Answer 40

Hepatic glycogenolysis, adipose release of FFA, muscle and liver use FFA, hepatic gluconeogenesis

Question 41

Starvation >3days

Answer 41

Adipose stores mostly. Ketone bodies dominate brain energy source. Afterwards, vital protein degradation accelerates.

Question 42

Key enzymes of lipid transport?

Answer 42

Pancreatic lipase - degrades dietary TG's in small intestineLipoprotein lipase - degrades TG's in chylo and VLDL's. Found on vasculature.Hepatic TG lipase - degrades TG's in IDLHormone-sensitive lipase - degrades TG in adipocytesLCAT - catalyzes esterification of cholesterol (makes nascent HDL -> mature HDL)CETP - transfers cholesterol esters from mature HDL to other lipoproteins

Question 43

Main purpose of Chlyomicrons, VLDL, LDL, HDLs

Answer 43

Chylos take dietary lipid to tissues. VLDL's deliver hepatic TG's to peripherals. LDL delivers hepatic cholesterol to peripheral tissues (receptor-mediated endocytosis). HDL takes excess tissue cholesterol back to liver.

Question 44

Major apolipoproteins

Answer 44

E - remnant uptakeA-I - activates LCATC-II - lipoprotein lipase cofactorB-48 - chylomicron secretionB-100 - binds LDL receptor

Question 45

Familial dyslipidemias

Answer 45

I - hyperchylomicronemia. AR. Lipoprotein lipase deficiency or altered C-II. Pancreatitis, hepatosplenomeg, xanthomas.IIa - familial hypercholesterolemia. AD. LDLR. Heteros have chol 300, homozys with 700+. Acc. atherosclerosis, tendon xanthomas, corneal arcusIV - hypertriglyceridemia. AD. Overproduction of VLDL. Pancreatitis.