Urea cycle occurs in which two places
mitochondria
cytosol
cytoplasm
ECM
mito and cytoplasm
5 enzymes of the urea cycle
which 2 need ATP
CPS1 - carbomyl phosphate (2 ATP) OTC - ornithine trans-carbonmylase ASS - argino-succinate synthetase (1 ATP) ASL - argino-succinase lyase A - arginase
AA —-> transamination —-> a-keto acid (which will be used in all metabolic intermediates for energy)
what molecule is involved in this process - ultimately leading to glutamate?
a-KG
PLP enzyme - what does it do?
what are the 2 products of the reaction it’s in charge of?
COFACTOR: active Vit B6 - carbon and oxygen molecule swapping
alanine (AA) + a-KG (keto acid) —–AAT——> pyruvate + glutamate
AAT - alanine aminotransaminase (second reaction when the molecule is being broken down further (aspartate); the enzyme is ASPARTATE AT
glutamate DH - converts a-KG to?
glutamate
IN MUSCLE
glutamate + ATP + NH4 —> ______ + ADP
what enzyme?
glutamine
glutamine synthetase
IN LIVER - OXIDATIVE DEAMINATION
glutamine –> NH4 + glutamate via - which enzyme?
glutamate (now inside the liver) —> a-KG + NH4 - which enzyme? thus releasing what?
glutaminase
glutamate DH - releasing that ammonia
__ ATP per aspartate = _ATP/nitrogen
4
2
Which one of these activates CPS1?
arginine
glutamate semialdehyde
ornithinine
n-acetyl-glutamate
N-A Glutamate (sole purpose in life to activate CPS1)
Hemodialysis
means of decreasing ammonia in body and blood
Folic acid is key to what?
nucleotides - prevent neural tube defects
N5, N10 - METHLENE-TETRAHYDROFOLATE
wtf is this?
active form of folate
Cystathionine synthase - related to what condition?
homocystinuria
homocystine build up (cannot make cystine)
Phenylalanine hydroxylase and dihydrobiopterin reductase - related to what condition?
phenylketonuria
Phenylalanine hydroxylase also associated with what other AA’s catabolism?
tyrosine
polyphenol oxidase added to urine of patients with this condition - leading to black urine
alcaptonuria - related to melanin
Uric acid is formed from the breakdown of pyrimidines or purines?
purines
T or F: glutamate has no role in NT
F
When the body is infected - positive or negative N balance?
-ve
2 purine bases
3 pyrimidine bases
adenine - guanine
uracil, thymine, cytosine
What happens if you cannot methylate uracil?
death - cannot replicate DNA
Ribose + 5-P + ATP –> AMP + _______? via what enzyme?
PRPP
PRPP synthetase
de novo purine synthesis
what is the key controlling enyzme?
glutamine phosphoribosyl amidotransfrase
When making _MP = ATP is the energy source and glutamine is the nitrogen donor
When making _MP = GTP is the energy source and aspartic acid is the nitrogen donor
ATP Cost
Costs __ GTP to form AMP
Costs __ ATP to form GMP
GMP
AMP
1
2
What enzyme aids in the production of deoxyribonucleotide (removes hydroxyl group from hte sugar)
ribonucleotide reductase
____ will shut the enzyme down, a nucleotide will encourage other deoxyribonucleotides to be produced
dATP
Purine Metabolism (Diseases)
SCID (Severe Combined Immunodeficiency) - what enzyme is dysfunctional?
SCID (Severe Combined Immunodeficiency)
o Adenosine deaminase is nonfunctional
o Can’t remove amino group from adenosine and convert adenosine to inosine o Deoxyadenosine and derivatives build up
o Loss of immune function – No T and B cells
o Cells can’t divide because we can’t replicate DNA
Purine Metabolism (Diseases)
Lesch-Nyan Syndrome - what enzyme is dysfunctional?
• Lesch-Nyan Syndrome o Hypoxanthine guanine phosphoribosyltransferase is nonfunctional o Increased levels of PRPP o Decreased levels of GMP and IMP o Increased de novo purine synthesis o Purines and uric acid build up o Potential for gout o Mental retardation o Self mutilation
Purine Metabolism (Diseases)
Primary Gout - what enzyme is dysfunctional?
Primary Gout
o PRPP insensitive to feedback control
o HGPRT reduced (salvage pathway)
o Uric acid build up
o Pain in the joints - Often times severe pain in the big toe
o It often happens after a person has been partying – rich meals with lots of protein (DNA) and they go to bed and get
this terrible pain in the middle of the night in their big toe
o
Purine Metabolism (Diseases)
Von Gierke’s Disease - what enzyme is dysfunctional?
Von Gierke’s Disease
§ Glucose 6 phosphatase and the transporter protein that allows G6P to enter the ER are not functioning
§ G6P builds up, encouraging the hexose monophosphate shunt which gives ribose 5 phosphate
§ Build up of Ribose 5P that leads to an excess of PRPP, which can override the controls for purine synthesis
and produce more IMP and GTP than necessary
§ The resultant nucleotides are not needed so they must be degraded which increases uric acid
Purine Metabolism (Diseases)
Secondary gout - what enzyme is dysfunctional?
• Secondary Gout
o Diet and lifestyle play a role
o The kidney is not able to excrete uric acid as sufficiently as it should
o Initially it can give pain in the big toe
o Pain is so severe that the individual cannot sleep
o Genetic propensity for a build-up of uric acid
o If someone is overweight, circulation is not as good as it used to be
o Alcohol has a negative effect
o Can lead to dehydration
o Decrease in excretion of uric acid by the kidney
o Caviar can lead to increased risk of gout
o Gout attack can occur as they are lying down
o King’s were susceptible
o Lots of good food without any physical activity
o Kidney disease can also have an effect on gout
o Lifestyle changes are the best way to deal with gout
o Pharmaceuticals can be used
o Can also occur as a result of:
o Leukemia
o Chemotherapy
o Multiple myeloma
o Lead poisoning
o Kidney disease
Tx for 2ndary gout = allopurinol; blocks what enzyme
xanthene oxidase
T or F: folic acid is not involved in pyrimidine base
T
T or F: carbamoylphospate synthetase I is one of the enzymes involved in pyrimidine formation
F - this is solely related to urea synthesis
Build up of urea in the blood?
kidney failure
build up of ammonia in the blood
liver failure