Nitrogen Metabolism II (Week 13)

Nitrogen, NH3, NH4+

Metabolic targets from urea cycle

Liver

Urea is made in the…

Hyperammonemia, urea, neurological

__ (condition) is a defect in the __ cycle due to excess ammonia will cross blood brain barrier and lead to __ sx

Nitrogen, ammonia, urea, urine

Urea Cycle

• Most of the __ in converted to urea in the liver

• Toxic nitrogenous waste products such as __ (very toxic) is converted to __ (non-toxic, soluble)

  • Excreted in the __

Glutamine and alanine

2 AA groups carrying NH3 and NH4+ to liver for synthesis of new proteins

Transamination

An amino group from one amino acid becomes the amino group of a second amino acid; remove nitrogen

Glutamate dehydrogenase, alpha-ketoglutarate

Glutamate is oxidatively deaminated by reaction catalyzed by __ __ (enzyme), producing ammonium ion and __- __

Transaminases/aminotransferases

Enzymes for transamination are…(2 names)

Tissues, muscle

Glutamate is in the __ (blood/tissues) of the body

Alanine is primarily exported by the __

Glucose–alanine cycle

Cycle of moving carbons and nitrogen between muscle and liver

Ammonium, tissues, nitrogen, liver, nitrogen, ammonium, urea

• Glutamate captures __ ion in all the __ (tissues/blood)

• During increase amino acid degradation, formed glutamate accepts another __ molecule to form glutamine

• Glutamine goes in the __

• Glutamine then removes a __ and __ ion out in liver

• Now is able to enter __ cycle

Carbamoyl phosphate synthetase I (CSPI)

First urea cycle enzyme making carbamoyl phosphate

Severe hyperammonemia

Absence of CSPI enzyme leads to…

Ornithine transcarbamoylase (OTC)

Carbamoyl phosphate reacts with ornithine to form citrulline by this enzyme

Carbamoyl phosphate synthetase II (CSPII)

Carbamoyl phosphate in the cytoplasm is metabolized to form uracil, orotic acid, or uric acid

→ Leads to gout and elevated ammonia if missing

OTC deficiency

Leads to hyperammonemia and gout/orotic acid

Arginosuccinate synthetase

Enzyme condenses citrulline with aspartate to form arginosuccinate in cytosol

Arginosuccinate synthetase deficiency

Leads to hyperammonemia and high cirtrulline

Arginosuccinate lyase

Enzyme splits argininosuccinate into arginine and fumarate in cytosol

Arginosuccinate lyase deficiency

Leads to slight hyperammonemia and high arginosuccinate

Arginase

Cleaves arginine into one molecule of urea and ornithine in the cytosol

Arginase deficiency

Leads to slight hyperammonemia and high arginine

Ammonia, glutamate

Ammonia toxicity occurs by osmotic imbalance leading to increased __ and __ in the astrocytes of brain

Urease

Enzyme that catalyzes the hydrolysis of urea, forming ammonia and carbon dioxide

CPS I deficiency Sx

high ammonia levels, brain damage, coma, death

X-linked

OTC deficiency with neurological sequelae and gout is … (genetic inheritance)