Biochem CIS Flashcards
in bloodstream
single amino acids
then transpored into cells
amino acid metabolism
need to excrete nitrogen - urea
carbon as energy
urea
from urea cycle in liver
uric acid
from purine bases
creatinine
from creatine phosphate
ammonia
from glutamine in kidney
bilirubin
from heme
nitrogen to be excreted
urea uric acid creatinine ammonia bilirubin
fed state
amino acids brought in by digestion
- go to liver
- carbon to glucose of TAGs
to liver - hepatic portal - as single AAs in blood stream
fasting state
amino acids released from protein breakdown
release single AAs from proteins in body - major source muscle
shuttles in blood - carrier AAs - glutamine and alanine**
albumin
created by liver
-one of main uses of amino acid nitrogen in the liver
glutamine
transport of nitrogen to kidney
ammonia
alanine
transport of AAs to liver
for urea
case - 21yo M, loss of appetitive, N/V, joint pain, abdomen pain, ice tea colored urine, clay colored stool, caribbean travel recent, jaundice, enlarged and tender liver
ALT and AST very high
alk phos high
bilirubin high
positive IgM anti-HAV
sent home
6 weeks later, vomiting, jerking, grimacing, altered LOC, ALT, AST, alk phos, bilirubin increased - admitted to hosp
travel - hepatitis A - from food
sent home - no real tx for Hep A
avoid tylenol - acetaminophen hepatotoxic
at 6 weeks - see necrosis with acetaminophen and the hepatitis
-hyperammonemia
hyperammonemia
caused by liver failure - or hepatotoxicity due to inflammation
sx - brain swelling - osmotic imbalance
high ammonia in brain
alters osmotic balance - causes brain swelling
high ammonia and glutamate in astrocytes
initiates glutamine synthetase and inhibits glutaminase
astrocytes produce glutamine
glutamate
central to urea production
-provides nitrogens for urea cycle
one from ammonium ion
one from aspartate
transamination rxn
transfer of nitrogen in form
convert amino acid to its alpha-keto acid
is reversible
glutamate
produced from alpha-ketoglutarate + any other AA
steal N from AA
glutamate transfers N to other molecule via second transamination
-if to oxaloacetate - to make aspartate
alpha-keto acid of aspartate
oxaoacetate
glutamate
for transamination rxn
nitrogen carriers
alanine
glutamine
alanine
specific to muscle
-pyruvate** transaminated to alanine
alanine then to liver
glutamine
in liver, muscle, somatic cells
-from glutamate
glutamine
is one more nitrogen to glutamate
alpha-KG - 0 N
glutamate - 1 N
gultamine - 2 Ns
urea cycle
in liver
-nitrogen source - ammonium or aspartate
in mito - carbmoyl phosphate from free ammonium ion - react with ornithine
-produce cirtuline - crosses mito membrane to cytosol
in cytosol - aspartate plus citrulline to arginossuccinate - produce agrinine - release urea and regenerate ornithine
low blood cirtulline
defect in carbamoyl phosphate synthetase and ornithine transcarbamoylase
low blood arginine and high cirtulline
defect in arginosuccinate synthetase or arginosuccinate lyase
high blood arginine and high cirtulline
arginase defect
orotate
produced from excess carbamoyl phosphate
-with ornithine transcarbamoyl phosphate accumulation
carbamoyl phosphate
created in mito to allow ammonia to enter urea cycle
will build up - with ornithine transcarbamoyl deficiency
results in orotate increase**
orotate
defect in ornithine transcarbamoylase
Case - 12yo male sudden seizure, left side weakness, PMH special eduation group, surgery for downward lens dislocation of eyes
CAT scan - small infarction - right cerebral hemisphere
3 days - left sided weakness cleared
osteopenia, waddling gait, increased length of long bones and scoliosis
high methionine
no cystine
elevated homocystine and homocysteine
normal B12 and folate
24 hour urine homocystine elevated
probably congenital
defect in pathway to form cystine
homocystinuruia
homocystinuria
auto recessive
deficient in cystathione synthase
CV disease and developmental anomalies, mental retardation
marfanoid habitus - says not vit deficienct - probably not that chronic
no cystine, elevated methioneine, elevated homocysteine
homocystinuria
defect in cystathione synthase
methionine and cystine
has sulfur
methionine - essential AA
B12 and folate
for homocysteine methyltransferase - homocysteine** to methionine
defect - see low methionine and high homocysteine
PLP
pyrodoxal phosphate
-activated vit B6
cystathione beta-synthetase
requires PLP - vit B6
homocysteine** to cystathione
degradation of AAs
glucogenic - to glucose
- intermediates of TCA cycle
- all the non-essential AAs
ketogenic - to ketone bodies
-acetyl-CoA and acetoacetate
lysine and leucine
strictly ketogenic**
positive nitrogen balance
growth
incorporated exceeds excreted
negative nitrogen balance
malnutrition
excreted exceeds incorporated
Case 24 month old to clinic, Uganda, edema, distended abdomen, hypopigmented hair, dry skin
given oral rehydration for 12 hours
given infant formula and MTVs
malnutrition
kwashiorkor
marasmus
total calorie reduction
low weight, loss of body fat and muscle
kwashiorkor
protein malnutrition
adequate calorie - but protein deprivation
normal body weight
child has edema
arginine
only essential AA during period of growth
not in adults
non-essential AAs
from glucose
tyrosine from phenylalanine
tx of homocystinuria
PLP - vit B6
required for transamination rxns
methionine synthesis
vit B12 and folate
Case 47yo M to ED, alcoholic, binging without eating, slurred speech, sweating, HR 110, grand mal seizure
blood glucose - low
blood ethanol - elevated
alcoholic hypoglycemia
metabolism of alcohol - rapid to acetaldehyde - to acetate
-requires NAD+
NAD + is also required for gluconeogenesis - so this cannot occur with lots of ethanol
alcoholic hypoglycemia
metabolism of alcohol utilizes NAD+
no gluconeogenesis can occur - bc also requires NAD+
occurs with increased NADH/NAD+ ratio
maintenance of blood glucose levels
by liver
-glycogenolysis - fasting - 12 hours
-gluconeogenesis - starvation - only source after 24 hours of fasting
gluconeogenesis and glycolysis
most steps are reverse of one another
precursors lactate, alanine, glycerol 3 P
lactate
oxidized to pyruvate
from anaerobic glycolysis
alanine
converted to pyruvate
alanine aminotransferase
from breakdown of proteins
glycerol 3 P
oxidized to DHAP by glycerol 3 P DH
from FAs - adipose tissue
irreversible steps in glycolysis
4 rxns
PEP to pyruvate
- OAA reduced to malate
- requires NAD+
one more?
fructose 1,6 hisphosphatase
glucose 6 phosphatase
glucose 6 phosphatase
only in liver - so only place for gluconeogenesis
converts glucose to enter bloodstream
alpha 1, 6 bonds
branching of glycogen
