Amino Acid Metabolism 2 Flashcards
Urea cycle produes urea to detoxify _____
NH4+ (Ammonia)
Where does the urea cycle begin?
Mitochondria
In addition to urea, what other important product is generated via the urea cycle?
Arginine
___ ATP molecules are used in the mitochondria to produce carbamoyl phosphate
___ ATP molecules are used in the cytosol to produce argininosuccinate from citrulline.
2
1
____ is required to activate carbamoyl phosphate synthetase 1 and links the TCA cycle and amino acid metabolism.
Acetylglutamate
What do high levels of glutamate indicate?
What impact does this have on TCA cycle?
Considering this, explain how the TCA cycle and Urea cycle are linked.
High levels of amino acid metabolism for energy use that is outpacing the pace of the urea cycle
In order to deal with the nitrogen in AAs, AKG is converted to glutamate, so there is a decrease in AKG which will result in decreased flux through TCA.
Urea cycle decreases [glutamate] and in glutmate metabolism AKG is produced, so the urea cycle can restore the balance of TCA cycle intermediates by increasing [AKG] and allowing TCA to continue
Acetyl coA levels will _____ if AKG is converted to Glu.
Increase
What is the major presentation of urea cycle defects?
Hyperammonemia
Ornithine transcarbamylase deficiency is inherited via ______ inheritance
Deficiencies in other urea cycle enzymes are inherited via ______ inheritance
X-linked
Autosomal recessive
Ammonia is highly toxic to the ______ system
Nervous
Defects in urea cycle enzymes are noticed at what stage of life?
1 - 2 days after birth (poor feeding, vomiting, coma, seizure)
Ornithine transcarbamylase deficiency leads to production of ______
Orotic acid
How does OTC deficiency impact pyrimidine synthesis?
When OTC is deficient, carbamoyl phosphate builds up and can leak from the mitochondria and impact pyrimidine biosynthesis
How can hyerammonemia be treated using conjugates that are administered to a patient (2)?
1) In the body: ammonia can be added to glycolytic intermediate to make glycine
Drug: benzoate given –> combines with glycine to be excreted safely
2) In the body: ammonia can be added to glutamate to make glutamine
Drug: Pehnylacetate given –> combines with glutamine to be excreted safely
The kidney can take up glutamine from the blood and convert it to glutamate producing NH4+. Why does it do this?
Removal of NH3 from glutamine allows the kidney to combine NH3 with H+ to produce NH4+ and thus excrete excess H+ ions in times of high [H+] in blood. Thus, the kidney produces urea directly in order to maintain pH balance.
Describe the reason why the kidney performs gluconeogenesis.
Glutamate produced from glutamine degradation in kidney is converted to AKG by glutamate dehydrogenase in kidney. AKG feeds into gluconeogenesis pathway in kidney (kidney has enzymes for Gluconeogenesis). Thus, kidney is CONSTITUTIVELY performing gluconeogenesis because it is always maintaining pH balance so it is always generating AKG.
____ is used to synthesize tyrosine.
Phe
Tyrosine is non-essential as long as ___ is in excess.
Phe
Degradation of tyrosine releases ___ and results in production of ___.
Fumarate
Acetyl-coA
PKU is a defect in which enzyme?
Phenylalanine hydroxylase, which is needed to make tyrosine from Phe
Untreated PKU is associated with ______
Intellectual disability
PKU Defects
- Patients with this defect present with ___?
- What is the treatment for PKU?
- What is a clinical sign of PKU?
- Hyperphenylalaninemia and phenylketonuria
- Phe restricted diet
- Musty smelling urine
Alkaptonuria is a defect in the breakdown of ______. The result is a build up of ______.
Tyrosine
Homogenistic acid
What happens to the urine and bones in alkoptonuria?
- Urine turns black upon standing
- Build up of homogentisate results in polymerization and formation of dark pigment that is deposited in cartilage and turns joints black
What 2 compounds is tyrosine a precursor for?
Catecholamines and melanin
