1231 Flashcards
(45 cards)
Galactose metabolism?
Most commonly from lactose (glucose-galactose), with lactase in GI breaking down. Galactose -(galactokinase)-> galactose-1P -(Uridyltransferase)-> Glucose-1-P
Galactokinase deficiency?
AR. Galactose in blood and urine. Galactitol accumulation (via aldose reductase) -> infantile cataracts (failure to track or develop social smile).
Classic galactosemia
AR. Absence of galactose-1-phosphate uridyltransferase. Galactitol accumulation (via aldose reductase) -> cataracts. FTT, jaundice, hepatomegaly, ID. Tx = exclude galactose and lactose.
Sorbitol
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.
Lactase deficiency
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.
What aa’s found in histones?
Positively charged (basic) Arginine and lysine.
Glucogenic aa’s v. Ketogenic aa’s?
Met, Val, His v. Leu, Lys; Ile, Phe, Thr, Trp are both.VeHeMetly sugary. Kato went to LaLa land.PITT - best of both worlds.
Rate limiting enzyme of urea cycle?
Carbomyl phosphate synthetase I. In mitochondria. CO2 + NH3 + 2ATP -> Carbomyl phosphate
Urea Cycle?
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).
How does ammonia from muscle get to the liver?
Turned into alanine before transported to liver for transamination into pyruvate + glutamate (->-> urea)
AST and ALT do what?
Asparate + alpha-ketoglutarate oxaloacetate + glutamate
Alanine + alpha-ketoglutarate pyruvate + glutamate
Hyperammonemia
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.
Hereditary hyperammonemias
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
Phenylalanine, Tryptophan, and Histidine make what important compounds?
Phe - Thyroxine, Melanin, Dopamine, NE, EpiTry - Niacin, NAD, Serotonin, MelatoninHis - Histamine
Glycine, Glutamate, Arginine make what important compounds?
Gly - Porphyrin, hemeGlut - GABA, glutathioneArginine - Creatine, Urea, Nitric oxide
Overview of Phenylalanine/Tyrosine catabolism?
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
Alkaptonuria
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)
Homocystinuria
Homocystein in urine, ID, osteo, tall, kyphosis, lens, atherosclerosis.Varied etio - Cystathionine synthase deficiency, homocysteine methyltransferase deficiency, dec. pyridoxal phosphate binding to cystationine synthase
Cystinuria
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.
Maple Syrup Disease
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
Glycogen regulation by insulin and glucagon/epi?
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.
Glycogenolysis?
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
Glycogenesis?
Glucose 1-P -(UDP-glucose pyrophosphorylase)-> UDP-glucose -(glycogen synthase)-> glycogen;Links are alpha-1,4 while branches are alpha-1,6
Glycogen storage disease (four of them)
Very Poor Carbohydrate MetabolismVon Gierke (most common), Pompe, Cori, McArdle (V)