Lipid metabolism and urea cycle

Question 1

conjugation

Answer 1

addition of glucuronic acid -> bilirubin diglucuronide

catalyzed by UDPGT

Question 2

urobilin

Answer 2

yellow

in urine

Question 3

sterobilin

Answer 3

brown in feces

Question 4

catabolism of hemoglobin

Answer 4

heme -> biliverdin via heme oxygenase uses O2 produces CO2
biliverdin -> bilirubin (insoluble) via biliverdin reductase needed NADPH
conjugated in liver

Question 5

bacterial beta glucuronidases

Answer 5

hydrolyze conjugated bilirubin back to unconjugated

Question 6

urobilinogens

Answer 6

stercobilinogen -> stercobilin
mesobilinogen -> mesobilin
urobiliogen -> urobilin
about 20% reabsorbed into entero-hepatic ciculation

Question 7

jaundice

Answer 7

bilirubin exceeds 2-3mg/dL
infants get kernicterus when exceeds 15-20mg/dL
can lead to brain damage

Question 8

hemolytic anemia

Answer 8

excess hemolysis
large increase in unconjugated bilirubin
increase in conjugated bilirubin

Question 9

hepatitis

Answer 9

large increase in both conjugated and unconjugated

Question 10

biliary stone

Answer 10

large increase in conjugated

small increase in unconjugated

Question 11

pre-hepatic jaundice

Answer 11

aka hemolytic jaundice
excessive bilirubin presented to licer
increased total 
large increase in unconjugated
negative urine bilirubin
urinary urobilinogen high

Question 12

intra-hepatic jaundice

Answer 12

can be caused by:

• gilberts syndrome
• crigler-najjar type I syndrome
• dubin-johnson sundrome
• hepatitis

Question 13

gilberts syndrome

Answer 13

enzyme mutation: UDP-glucuronyltransferase gene 
impaired hepatocellular uptake
total <3mg/dL, mostly unconjugated
increased urinary urobilinogen
mild jaundice

Question 14

crigler-najjar type I syndrome

Answer 14

incomplete absence of UDP-glucuronyltransferase 
defective conjugation
serum unconjugated >25mg/dL
increased urninary urobilinogen
fatal w/in 1 yr w/o liver transplant

Question 15

dubin-johnson syndrome

Answer 15

defective secretion by hepatocytes
increased conjugated
liver has characteristic green-black color

Question 16

hepatitis

Answer 16

increased both

total 5-10 mg/dL

Question 17

post hepatic jaundice

Answer 17

mechanical obstruction of flow
increased serum and urine conjugated bilirubin
decreased urobilin/stercobilin in stool (clay colored stool)
negative urinary urobilinogen

Question 18

high conjugated

Answer 18

dubin-johnson
rotor
post-hepatic

Question 19

high unconjugated

Answer 19

gilberts 25
ciglner-najjar II -5-20 mg/dL
lucey-driscoll- transiently around 5 mg/dL

Question 20

ciglner-najjar II

Answer 20

partial deficiency of UDP-glucuronyltransferase
unconjugated 5-20
responds to phenobarbital
normal life

Question 21

rotors syndrome

Answer 21

similar to dubin-johnson w/o pigementation of liver
high conjugated
moderate jaundice

Question 22

amino acid oxidation

Answer 22

leftover AA from normal protein turnover degraded
dietary AA that exceed bodys needs degraded
proteins in body are broken down to supply AA for catabolism when carbs are in short supply

Question 23

nitrogen elimination

Answer 23

transamination or aminotransferase rxns

release of N from glutamate and its conversion to urea by urea cycle in liver

Question 24

enzymatic transamination

Answer 24

all aminotransferases rely on pyridoxal phosphate cofactor
typically alpha-ketoglutarate accepts amino groups
L-glutamine acts as temporary storage of N
L-glutamine can donate the amino groip when needed for amino acid biosynthesis

Question 25

glutamate dehydrogenase

Answer 25

uses NADH to combine alpha-ketoglutarate and amino group to form glutamate

Question 26

glutamine synthetase

Answer 26

uses NH3 + ATP to convert glutamate to glutamine

Question 27

step 1 urea cycle

Answer 27

carbamoyl phosphate + ornithine -> citrulline via ornithine transcarbamoylase in matrix, passes into cytosol

Question 28

step 2 urea cycle

Answer 28

citrulline converted to argininosuccinate | via argininsuccinate synthetase

Question 29

step 3 urea cycle

Answer 29

arginocuccinate cleaved -> fumarate and arginine via argininosuccinase these enter TCA cyle

Question 30

step 4 urea cycle

Answer 30

arginine converted to urea and ornithine via arginase

Question 31

urea cycle

Answer 31

primarily in liver, some in kidney L-glutamie can be used to synthesize new AA or it can dispose of excess N as ammonia nitrogen added to urea cycle via carbamoyl phosphate and aspartate

Question 32

urea cycle enzymes in mito

Answer 32

carbamoyal phosphate synthetase | ornithine transcarbamylase

Question 33

urea cycle enzymes in cytosol

Answer 33

argino-succinate synthase agrino-succinase arginase

Question 34

PKU

Answer 34

autosomal recessive deficiency in PAH increase in phenylalanine and phenylpyruvate, both toxic to CNS

Question 35

PAH

Answer 35

metabolizes phenylalanine to tyrosine and epiephrine | w/o PAH phenlyalanine -> phenylpyruvate

Question 36

released w/liver damage and levels elevated

Answer 36

ALT (alanine transaminase) , AST (aspartate transaminase) , ALP (alkaline phosphate), GGT (gamma-glutamyltransferase), LDH (L-lactated dehydrogenase)