Flashcards in Biochemistry Deck (255)
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. Activated by N-acetylglutamate (formed by enzyme N-acetylglutamate synthetase from acetyl-CoA and glutamate).
Carbomyl phosphate + ornithine -(ornithine transcarbamylase)-> citrulline + Asp + ATP -(argininosuccinate synthetase)-> argininosuccinate -(argininosuccinase)-> arginine + (fumarate) -(Arginase)-> Urea + ornithine
Point 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?
ASP + alpha-ketoglutarate -> oxaloacetate + glutamine; Alanine + alpha-ketoglutarate -> pyruvate + glutamine.
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.
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.
Phenylalanine, Tryptophan, and Histidine make what important compounds?
Phe - Thyroxine, Melanin (tyrosinase), Dopamine (DOPA decarboxylase), NE, Epi; Try - Niacin, NAD, Serotonin, Melatonin; His - Histamine
Glycine, Glutamate, Arginine make what important compounds?
Gly - Porphyrin, heme; Glut - GABA, glutathione; Arginine - Creatine, Urea, Nitric oxide
Overview of Phenylalanine/Tyrosine catabolism?
Phe -(phenylalanine hydroxylase, BH4)-> Tyr; PKU |_|Tyr -(tyr hydroxylase,BH4)-> DOPA -(DOPA decarboxylase, B6)-> dopamine-(r. VitC)-> NE -(r. SAM)-> Epi -> Metanephrine |_|
Dopamine -> homovanillic acid |_| NE -> Normetanephrine -> vanillylmandelic acid |_| DOPA -(tyrosinase)-> melanin; ALBINISM |_| Tyr ->-> homogentisic acid -(Homogentisate oxidase)-> Maleylacetoacetic acid -> TCA; 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)
Homocysteine in urine, ID, osteo, marfinoid, kyphosis, dislocated lens, atherosclerosis -> THROMBOEMBOLISM. Etios include cystathionine synthase deficiency (Cysteine becomes essential AA), homocysteine methyltransferase deficiency, dec. pyridoxal phosphate binding to cystationine synthase. Treatment with B6 helps a lot.
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. Adenylate cyclase pathway vs. Ca2+; Insulin inhibits glycogen phosphorylase via a phosphatase. And pushes glycogen synthase.
Glycogen phosphorylase removes branch down to 4 residues (Dextrins). 4-alpha-D-glucanotransferase moves 3 glucose-1P's, then alpha-1,6 glucosidase cleaves last one
Cleaves off glucose-1P -(glucose-6-phosphatase)-> Glucose-6-P
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 Metabolism: Von Gierke (most common), Pompe, Cori, McArdle (V)
Von Gierke disease (type I)
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.
Pompe disease (II)
LYSOSOMAL alpha-1,4-glucosidase (small amount of glycogen degraded via this method). Cardiomyopathy. AR. LYSE his head, he's so pompous.
Cori disease (III)
Alpha-1,6,glucosidase (last debranch). AR. Gluconeogenesis okay. Mild von Gierke.
McArdle disease (IV)
Skeletal muscle glycogen phosphorylase. AR. Increased Glycogen in MUSCLE but CAN'T break down-> cramps, MYOglobinuria with exercise, arrhythmias, weakness.
alpha-galactosidase A. Ceramide trihexoside. XR. Peripheral neuropathy, angiokeratomas, cardio/renal. AGA - American GI association, cuz Dr. Fabry was a dermatologist.
Glucocerebrosidase (B-glucosidase). Glucocerebroside. AR. Hepatosplenomegaly, pancytopenia, GAUCHER cells (lipid-laden macrophages!). Recombinant glucocerebrosidase available tx. Gaucher is a Cerebral!
Hexosaminidase A. GM2 ganglioside. AR. CHERRY-Red spot on macula. No hepatosplenomegaly. A HEX on the people.
Galactocerebrosidase. Most Cerebral of the Galactosy. AR. Peripheral neuropathy, dvpt delay.
Arylsulfatase. Central and peripheral demyelination with ataxia, dementia. Many-colored Arya faces sulfur pits.
alpha-L-iduronidase. AR. Heparan sulfate. Dvpt delay, gargoylism, airway, corneal. iDuron duran is a hurler.