Biochemistry - Urea Cycle

Front 1

Where does the urea cycle take place?

Back 1

The liver

Front 2

Liver damage can lead to ________

Back 2

toxic hyperammonemia

Front 3

What structure does hyperammonemia have the most severe effect on?

Back 3

the brain

Front 4

What is the purpose of the urea cycle?

Back 4

To detoxify ammonia and form urea. Urea contains two N's that can be released via the kidney into the urine

Front 5

Where in the cell does the urea cycle take place?

Back 5

mitochondria and cytosol

Front 6

Urea cycle regulation

Back 6

Enzyme induction after a meal or during starvation. Regulated enzyme: carbamoyl-P synthetase I which needs N-acetyle glutamate as an absolute activator. Arginine and glutamate are the main players in the activation of the cycle

Front 7

What is the regulated enzyme in the urea cycle?

Back 7

carbamoyl-P synthetase I

Front 8

What is the absolute activator of carbamoyl-P synthetase I?

Back 8

N-acetyl-glutamate

Front 9

Most tissues release which two amino acids into the blood?

Back 9

alanine and glutamine

Front 10

How is alanine formed?

Back 10

Transamination of pyruvate that is generated in glycolysis

Front 11

What are the advantages of glutamine?

Back 11

It transports two nitrogens in its structure and the synthesis of glutamine can be used to trap free ammonia into a harmless molecule (glutamine synthetase has a low Km, high affinity for free ammonia)

Front 12

What is needed for the formation of urea?

Back 12

free ammonia and aspartate in a 1:1 ratio. The carbon and oxygen are derived from carbon dioxide

Front 13

Uptake and deamination of what amino acid(s) generates free ammonia?

Back 13

glutamine and glutamate

Front 14

In most tissues, free ammonia is detoxified by what enzyme?

Back 14

glutamine synthetase

Front 15

After uptake of glutamine into the liver, what enzyme releases free ammonia?

Back 15

glutaminase

Front 16

The glutamate formed from the reaction of glutaminase can also be used to generate more ammonia using what enzyme?

Back 16

glutamate dehydrogenase

Front 17

Glutamate can also be used to form which amino acid for the urea cycle?

Back 17

aspartate

Front 18

What is the glucose-alanine cycle?

Back 18

Describes a cycle between liver and muscle. Liver releases glucose which can be used in muscle for glycolysis. Pyruvate can be transaminated to alanine using glutamate that was formed during the degradation of amino acids. Alanine is released from muscle into the blood and taken up by the liver. The carbon of alanine can be used after transamination for gluconeogenesis and the nitrogen is used for urea synthesis.

Front 19

What amino acid can be the product or the substrate in transamination?

Back 19

glutamate

Front 20

Oxidative deamination of ___________ catalyzed by glutamate dehydrogenase forms free ammonia and alpha keto glutarate.

Back 20

glutamate

Front 21

Oxidative deamination of glutamate by _____________ forms what?

Back 21

glutamate dehydrogenase, free ammonia and alpha ketoglutarate

Front 22

Enzyme induction can take place after what?

Back 22

high protein diet or during starvation. Otherwise the urea cycle is mainly regulated via availability of substrates

Front 23

What is the urea cycle mainly regulated by?

Back 23

availability of substrates

Front 24

High arginine levels stimulate __________ which forms urea and ornithine which enters liver mitochondria to continue the cyle

Back 24

arginase

Front 25

In the urea cycle, _________ enters the mitochondria

Back 25

L-ornithine

Front 26

High arginine levels in addition to high glutamate levels stimulate formation of _____________ which is the absolute necessary activator for ______________.

Back 26

N-acetyl-glutamate, carbamoyl-P synthetase I

Front 27

Glutamate has a central role in providing both ___________ (by transamination only using glutamate) and ____________ (which can also be provided by other amino acids)

Back 27

aspartate, free ammonia

Front 28

What is released in the urea cycle?

Back 28

fumarate

Front 29

The released fumarate can be used in liver cytosol to generate ___________ that is needed for the next round of the urea cycle

Back 29

aspartate

Front 30

What is hyperammonemia?

Back 30

blood ammonia levels above 1000 micromol/L, normal levels are 5 to 50

Front 31

What does ammonia intoxication include?

Back 31

tremors, slurring of speech, somnolence, vomiting, cerebral edema, and blurring vision

Front 32

What enzymes deplete the brain of glutamate and GABA?

Back 32

glutamate dehydrogenase and glutamine synthetase

Front 33

High glutamine levels in brain cells leads to what?

Back 33

cerebral edema

Front 34

Glutamate and GABA are what?

Back 34

neurotransmitters

Front 35

High concentration of ammonia in blood can cause what?

Back 35

lethargy, convulsions, coma and death

Front 36

Ammonia is also formed by intestinal bacteria using what enzyme?

Back 36

urease

Front 37

Some urea reaches the intestines, and the formed ammonia gets back into the liver via what?

Back 37

portal circulation

Front 38

If the liver cannot trap ammonia with ____________, then hyperammonemia can occur

Back 38

glutamate degydrogenase

Front 39

What can indicate a defect in the urea cycle?

Back 39

A combination of hyperammonemia, decreased blood urea nitrogen (BUN), and increased blood glutamine levels

Front 40

What is ornithine transcarbamoylase deficiency?

Back 40

X-linked genetic defect. Leads to high levels of carbamoyl-phosphate, which can leave into the cytosol. There it leads to uncontrolled, highly increased pyriidine synthesis that overwhelms the enzymes and the resulting high levels of orotic acid lead to orotic aciduria

Front 41

What symptoms do patients with ornithine transcarbaoylase deficiency (OTC deficiency) have?

Back 41

- Hyperammonemia
- Decreased BUN (blood urea nitrogen)
- High blood glutamine levels
- Orotic aciduria
- Cerebral edema, lethargy, convulsions, coma that can lead to death

Front 42

What is the treatment for hyperammonemia?

Back 42

- Low protein diet
- Treatment with compounds that bind to amino acids and are then excreted together int he urine

Front 43

What does benzoic acid do?

Back 43

Binds glycine and forms hippuric acid that is excreted in the urine

Front 44

What does phenylbutyrate do?

Back 44

Converted to phenylacetate (bad odor) inside the body. Phenylacetate then binds glutamine and phenylacetylglutamine and is excreted in the urine