Lightbody Lecture 18 Flashcards Preview

Biochem Unit 2 > Lightbody Lecture 18 > Flashcards

Flashcards in Lightbody Lecture 18 Deck (31):


NH3 prod by all tissues; disposed of primarily by form of urea in liver and removal by kidneys; must be kept low in blood b/c toxic; major sources are AAs, Glu, bact urease in intestine and catab of purines and pyrimidines; symptom of disease, not disease itself; brain suscep-->tremors, slur speech, vomit, cerebral edema, blur vision, coma and death


hyperammonia is a result of...

excess alcohol, viral infec, injury, toxic cmpnds, genetic defects, cancer, UCD, Reye's syndrome


CNS suscep to high [ammonia] - GD

NH3 crosses BBB; as rises, shifts Glu dehydrog rxn twd Glu formation; in normal conds, brain converts Glu to Gln, transports to liver; in hyperammon, GD uses lg amts of a-KG, then not avail in TCA to make ATP (needed to synth Gln from Glu)


CNS suscep to high [ammonia] - Glu

high [Glu] --> neuronal dmg and death; as NH3 rises in brain, Glu dehydrog rxn driven twd Glu-->excess Glu, which can't convert to Gln b/c lack of ATP; GABA synth'd from Glu; major inhib nt in brain, assoc w/Cl chans; high concs of GABA inhib depol of neurons


treat hyperammonemia

hemodialysis; limit prot intake; add cmpnds that can combine w/N cmpnds and are excreted in urine; ARG also inc ornithine, esp imp in type III and IV (where citrulline and arginosuccinate lost in urine); replace w/EAA (as a-keto acids to limit N intake) which can be formed into AA thru transamination


Ala cycle

enables musc (in starv, f.e.) to use AAs as E and to elim N (amino gp) by transporting it to the liver as Ala, where it's converted back to pyruvate and amino gp retransaminated to a-KG to give Glu


glutamate dehydrogenase

Glu + NAD+ + H2O --> a-KG + NH3 + NADH


glutamate synthetase

Glu + NH3 --> Gln



Gln + H2O --> Glu + NH3


relationship b/w Glu, Gln, a-KG

interconvertable; a-KG --> Glu --> Gln (add NH3 each time; if remove NH3, move from right to left)


Glu-Gln transition (cycle

transport NH3 from various tissues to the liver; raise pH in kidneys during acidosis; transport Gln into neurons where conv to Glu (Glu can't x BBB, but Gln can; after firing, Glu transported into glial cells, becomes Gln again (Gln synthetase), then retransported to neuron)


ketogenic AAs

Leu, Lys, Phe, Trp, Tyr, Ile, Thr; form acetoacetate or acetyl-CoA; provide lipids or E


glucogenic AAs

Arg, Gln, His, Pro, Ile, Met, Thr, Val, Phe, Tyr (GQHPIMTVFY); form pyruvate, OAA, fumarate, a-KG, or succinyl-CoA; provide lipids, E, glucose


both ketogenic and glucogenic AAs

Ala, Cys, Gly, Ser, Thr, Trp (ACGSTW); tyrosine


essential AAs



Met, homoCys, cysteine metab related

SAM donates methyl gps to RNA, DNA, prots, lipids, carb and nts; Coenz B12 nec for methionine synthase



no codon for Hcy, so not normally in prots, but occur by post-transl8 mod of Met; missing/impaired cystathione synthase-->homocysteinuria (assoc w/retardation, disorders of CT, mm, CNS, cardio); incidence of <3 attack and stroke inc w/high conc of Hcy in blood


cystathione synthase

converts serine and Hcy to cystathione; missing or defective in homocysteinuria


convert Phe to Tyr

PAH (Phe hydroxylase) catalyzes; def in this enz-->PKU (auto recessive) - retardation, don't thrive, can't walk/talk, seizures, hyperactivity, tremors, can't grow, light skin pigment; diet low in Phe and high in Tyr ctrls; diff to detect in infants b/c mom can clear excess from fetus thru placenta



req for oxygenase to convert Phe to Tyr; defect in enz that synths this results in PKU; severe mental retardation begins right after birth if Phe not reduced; py, lact, acetate compete w/AAs for receptor sites on chans that allow AAs to enter-->no prot formation-->retardation


maple syrup disease

branched chain AA metab defect; Val, Leu, Ile (brainched chain AAs) use same mech to decarbox as pyruvate decarboxylase; defect in branched chain AAs; auto recessive, defect in a-ketoacid dehydrogenase (2nd enz in degrad path in mito)


maple syrup disease symps

onset in 1st week; odor in urine; feeding diffs/vomit; hypertonic; suppressed tendon reflexes; freq convulsions; severe retardation and motor devel retardation; die in 1st month if untreated


maple syrup disease biochem and genetics

auto recessive, brkdn of endog prot resp for high levels of AAs; branched chain AAs and keto acids accum in organs, plasma, urine; severe neuro dmg and retardation appear b/c high concs of Leu in brain; odor b/c sotolon


Tyr biol products

DA (nt in brain, ANS; PD assoc w/DA in brain thru loss of neurons in basal ganglia); NE (nt in brain and ANS; horm, effects carb and lipid metab); epi (adrenaline - reg of carb and lipid metab); 25% of Phe goes to prot, 75% to Tyr


cmpnds derived from Trp

niacin; also serotonin formed in brain (nt), platelets, SMCs; drugs affecting serotonin treat depression, migraine, schizophrenia, OCD; serotonin --> melatonin


histamine from histidine

release CO2 w/decarboxylase to make histamine; synth in, rel by mast cells; med of allergic response (vasodil, bronchoconstric - H1 receps)


H1 blockers

diphenhydramine, loratidine



stim secretion of gastric acid


H2 blockers

cimetidine, ranitidine


synth of NO from Arg

Arg -*-> citrulline + NO (* = NOS)



signaling molec in humans and pollutant from engines; reacts w/O2 to prod nitric acid (acid rain); gas, prod by endothel of BVs; short t1/2; signals relaxation, dilates arteries, increase flow; induces cGMP formation; Viagra inhib cGMP degradation; nitroglycerin converts to NO; activate macs in infection; prevents platelet aggreg, nt in brain