Lightbody Lecture 18

Question 1

hyperammonemia

Answer 1

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

Question 2

hyperammonia is a result of…

Answer 2

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

Question 3

CNS suscep to high [ammonia] - GD

Answer 3

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)

Question 4

CNS suscep to high [ammonia] - Glu

Answer 4

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

Question 5

treat hyperammonemia

Answer 5

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

Question 6

Ala cycle

Answer 6

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

Question 7

glutamate dehydrogenase

Answer 7

Glu + NAD+ + H2O –> a-KG + NH3 + NADH

Question 8

glutamate synthetase

Answer 8

Glu + NH3 –> Gln

Question 9

glutaminase

Answer 9

Gln + H2O –> Glu + NH3

Question 10

relationship b/w Glu, Gln, a-KG

Answer 10

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

Question 11

Glu-Gln transition (cycle

Answer 11

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)

Question 12

ketogenic AAs

Answer 12

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

Question 13

glucogenic AAs

Answer 13

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

Question 14

both ketogenic and glucogenic AAs

Answer 14

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

Question 15

essential AAs

Answer 15

MILK TV FHW

Question 16

Met, homoCys, cysteine metab related

Answer 16

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

Question 17

homocysteinuria

Answer 17

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

Question 18

cystathione synthase

Answer 18

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

Question 19

convert Phe to Tyr

Answer 19

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

Question 20

BH4

Answer 20

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

Question 21

maple syrup disease

Answer 21

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)

Question 22

maple syrup disease symps

Answer 22

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

Question 23

maple syrup disease biochem and genetics

Answer 23

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

Question 24

Tyr biol products

Answer 24

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

Question 25

cmpnds derived from Trp

Answer 25

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

Question 26

histamine from histidine

Answer 26

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

Question 27

H1 blockers

Answer 27

diphenhydramine, loratidine

Question 28

H2

Answer 28

stim secretion of gastric acid

Question 29

H2 blockers

Answer 29

cimetidine, ranitidine

Question 30

synth of NO from Arg

Answer 30

Arg --> citrulline + NO ( = NOS)

Question 31

NO

Answer 31

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