Lightbody Lecture 17

Question 1

AAs

Answer 1

dietary, hydrol tissue prots, or de novo synth; const AA pool of 30g; not stored, but E source when prot catab in starvation; constant need for dietary AAs b/c 25% of AAs metab’d or serve as precursors for other cmpds; prots synth and degrad const (300-400g/d); 11 are nonessential

Question 2

AAs as precursors to…

Answer 2

prots, purines, primidine, HA, nicotinamide, AA Gly + acetate; nts; hormones; Glu, Asp, Gly are all nts by selves

Question 3

Glu and Gln synth

Answer 3

a-KG from TCA w/NH4+–> Glu w/NH4+ –>Gln

Question 4

Asp and Asn synth

Answer 4

OAA (TCA) w/ NH4+ –> Asp w/NH4+ –> Asn

Question 5

Ser and Gly synth

Answer 5

3P glycerate (glycol) w/NH4+ –> Ser w/release of MeTHF –> Gly

Question 6

Ser and Cys synth

Answer 6

3P glycerate (glycol) w/NH4+ –> Ser w/Met, supplies sulfur –> Cys

Question 7

Gly synth

Answer 7

NH4+ + HCO3- w/methylene THF –> Gly

Question 8

Ala synth

Answer 8

pyruvate (glyc) w/ NH4+ –> Ala

Question 9

Pro synth

Answer 9

Glu –> glutamate semialdehyde –> Pro

Question 10

Arg synth

Answer 10

NH3 + CO2 + ATP –> carbamoyl P –> urea cycle –> Arg (intermed in urea cycle, used up there, so semi-essential in adults, completely essential in kids)

Question 11

Tyr synth

Answer 11

Phe (essential) –> Tyr

Question 12

AA catabolism

Answer 12

presence of N in a-amino gp of AA prevents catabolism; dispose of a-amino gp thru transamination, deamination

Question 13

transamination rxns

Answer 13

remove a-amino gp in all AAs except Ser, Thr, Pro (STP); 1st step in catab of AAs; remove amino gp by funneling to a-KG to give Glu and form new a keto acid; all aminotransferases req pyridoxal phosphate (vit B6) - reversible (catab or ana) and spec for one amino gp donor; PLP forms Schiff base w/amino gp of Lys

Question 14

deamination rxns

Answer 14

remove a-amino gp thru oxidative (Glu dehydrog) or hydrolytic (Ser and Thr dehydratase)

Question 15

Ala aminotransferase (ALT/SPGT)

Answer 15

high [] in liver, smaller in <3 and musc; in musc, transfers amino gps from Glu to pyruvate to form Ala, which transports them to the liver; screens liver problems like hepatitis, mononucleosis, cirrhosis, drug tox like excess acetaminophen; ALt levels inc 20-50x in plasma when liver dmg

Question 16

Asp aminotransferase (AST/SGOT)

Answer 16

main fxn is to transfer amino gp from Glu to OAA–>Asp, which enters urea cycle (liver, heart, musc, kidney, brain)

Question 17

oxidative deamination

Answer 17

to Glu; results in liber of amino gp as free NH3; Glu acts as sink for amino gps of AAs thru transamin; amino gp converted to NH4+ by Glu dehydrogenase, regenerating a-KG to accept another amino gp; Glu transported from cyto to mito matrix (where this takes place)

Question 18

Glu dehydrogenase

Answer 18

converts amino gp of Glu to NH4+; also helps to release urea; reversible rxn dep on [] of Glu, aKG, and NH3; + by ADP, - by ATP

Question 19

Thr, Ser, Pro do NOT undergo transamination

Answer 19

Thr–>Gly + aCoA; Ser–>pyruvate + NH4+ +H2O; Pro–>Glu; a-amino of Lys undergoes transam, but other amino gp does not

Question 20

urea cycle

Answer 20

removes toxic ammonia, allowing AAs to be used as E; 90% of all N is removed via urea cycle; liver is major site (only tissue cont all 5 enz); other tisues have some enz’s, but only to make Arg and NO

Question 21

carbamoyl phosphate synthetase I (CPS I)

Answer 21

NH3 enters cycle as carbamoyl P in liver mito; NAG activates CPSI - required!;

Question 22

NAG

Answer 22

synth fr aCoA and Glu (N-acetylglutamine synthase) and + by Arg; as Arg levels inc, NAG inc and CPS I inc too

Question 23

CPS II

Answer 23

in cyto, req for pyrimidine biosynth; blocked OTCase results in excess of carbamoyl P, leaving mito and flooding pyrimidine path–>high conc of orotic acid in urine

Question 24

Ns in urea come from…

Answer 24

L-Arg

Question 25

argininosuccinate synthase

Answer 25

L-Asp to argininosuccinate; req ATP

Question 26

rel b/w TCA and urea cycle

Answer 26

argininosuccinate –> fumarate in cytosol, which becomes malate (which forms OAA) and enters mito matrix

Question 27

urea cycle disorders

Answer 27

1/30,000 live births; usu auto recessive, OTC X-linked; heteros asymp; less severe (partial deficiencies)–>fewer side effects, manifested in later childhood/adulthood

Question 28

severe illness–first week of UCD

Answer 28

usu normal first 24h; symps of hyperammonia in 1-3d; include feeding intolerance, vomit, lethargy, irritability, resp distress (hypervent), seizures, coma; 75% retardation, seizures, visual deficits, prot intolerance

Question 29

type I hyperammonia

Answer 29

CPSI deficiency; NH4 and GLN inc’d (defect in NAG synthase has same effect); visual deficits bad b/c high NH4; b/w carb P materials and carb P

Question 30

type II hyperammonia

Answer 30

OTC, X-linked, most common, high pyrimidine, metabolite (orotic acid); b/w carb phosphate/L ornithine and citrulline

Question 31

citrullinuria

Answer 31

arginosuccinate synthase leads to this; citrulline inc; b/w L-citrulline and L-argininosuccinate

Question 32

arginiosuccinic acidemia

Answer 32

b/w L-argininosuccinate and lyase/fumarate (no argininosuccinate breakdown)

Question 33

arginase deficiency

Answer 33

b/w L-Arg and L-ornithine; no urea