Liver Metabolism: Urea Cycle Flashcards
formation of bilirubin
Hg - to heme and globin
heme > biliverdin > bilirubin (direct)
carried to liver on albumin
UDPGT
uridyldiphosphate glucuronyl transferase
-conjugates bilirubin in liver at SER
adds glucuronide x2
heme oxygenase
heme > biliverdin
van den berg test
measure conjugated and unconjugated bilirubin levels
urobilinogen
converted in intestine (terminal ileum and colon)
colorless
20% reabsorbed
collection of sterco, meso, urobilinogen
normal range bilirubin
0.2-1
less than 0.2 conjugated
kernicterus
jaundice in infant - bilirubin > 15-20
-brain damage
aka brain encephalopathy
due to polycythemia, Rh incompatibility
pre-hepatic jaundice
excess hemolysis
hepatic jaundice
infection, drugs, alcohol, cirrhosis, pregnancy
post-hepatic jaundice
blockage of duct
cancer of bile duct, pancreas head
excess hemolysis
increased unconjugated and urinary urobilinogen
dark urine
total usually not > 5
biliverdin reductase
biliverdin > biliverdin
stercobilin
stool pigment
urobilin
in urine
causes of jaundice
excess bilirubin production
reduced hepatocyte uptake
impaired conjugation
impaired bile flow
gilberts syndrome
mild unconjugated hyperbilirubinemia
1.5-3
worse with stress
often misdiagnosed - chronic hepatitis
low activity of UDPGT (UGT 1A1 mutation)
crigler-najjar type I
absence of UDPGT
-very high unconjugated bilirubin
autosomal recessive
most patients die of kernicterus
Tx: early liver transplant
crigler najjar type II
autosomal dominant
partial deficiency UDPGT
unconjugated bilirubin elevated 5-20
responds to phenobarbitol
phenobarbitol
Tx for crigler najjar type II
dubin johnson syndrome
autosomal recessive
elevated conjugated
defective canalicular excretion
liver biopsy - black**
rotor syndrome
elevated conjugated
liver biopsy - normal
pepsin
stomach
trypsin
small intestine
aminopeptidase
carboxypeptidase
small intestine
excess AA sources
leftover
dietary
body protein breakdown
transamination
take away amino group (NH2)
glutamate
carries nitrogen 1
glutamine
carries nitrogen 2
pyridoxal phosphate cofactor
PLP
all aminotransferases use this cofactor
alpha-ketoglutarate
to glutamate
-by aminotransferase
takes NH2 from amino acid
L-glutamine
storage of NH2 x2
transport in blood to kidney
glutamine liberates NH2 groups in liver
glutamate dehydrogenase
alpha-ketoglutarate > glutamate
glutamine synthetase
glutamate > glutamine
carbamoyl phosphate synthetase I
glutamine > carbamoyl phosphate
deficiency leads to ammonia in blood
ornithine transcarbamoylase
carbamoyl phosphate + ornithine > cirtulline
deficiency - cant make urea
argininsuccinate synthetase
cirtulline > argininosuccinate
argininosuccinate
to fumarate and arginine
fumarate to citric acid cycle (makes ATP)
arginine to urea + ornithine
ornithine
recycled component of urea cycle
urea cycle chemical equation
3ATP + HCO3 + NH4 + asp > 2ADP + AMP + 2P + PP + fumarate + urea
argininosuccinase deficiency
protein depleted diet
supplement high levels of L-arginine
brain swelling
glutamine and glutamate are osmolites in brain
hepatic encephalopathy
PKU
deficienct phenylalanine hydroxylase
no phenylalanine to tyrpsine/Epi
phenylalanine to phenylpyruvate (both toxic CNS)
mental retardation occurs
-common ADHD
tested in newborns
aspartame
nutrasweet
-has phenylalanine
phenylalanine conversion
> tyrosine > L-dopa > dopamine > NE > E
BUN
blood urea nitrogen
liver and kidney function
higher - CHF, GI bleed, hypovolemia, kidney disease, shock
lower - low protein diet, malnutrition, over hydration
ALT, AST, ALP
elevated - liver damage
albumin and total protein
decreased - liver damage
GGT
elevated - liver or bile duct damage
LDH
elevated - liver damage
PT
increased - liver damage
MRP2
transport of direct bilirbubin to bile canaliculus
phototherapy
trans to cis unconjugated bilirubin
cis in yo piss
post-hepatic jaundice
no urobilinogen in urine (bc conjugated didnt go to intestine to get converted before reabsorbed)
however, conjugated bilirubin will be in urine
hepatitis
hepatic jaundice
damage of hepatocytes
elevated serum direct and indirect bilirubin
total reaches 5-10 mg/dL
