Unit 4: The Urea Cycle and Ketogenic and Glucogenic Amino Acids

NH4 and Asp

in the urea cycle, 2 nitrogen atoms are excreted and they come from:

combines CO2 and H2O ot form H2CO3 which can be ionized to HCO3

what does the enzyme carbonic anhydrase do?

-enzyme: carbamoyl phosphate synthetase 1

-reactants: HCO3 and NH4

-product: carbamoyl phosphate

cost of 2 ATP; 2 ATP -> 2 ADP and 2Pi

describe step 1 of the urea cycle

amino acids and aminotransferase enzyme

where does the bicarbonate and ammonia come from for step 1 of the urea cycle?

-enzyme: carbamoylase

-reactants: ornithine (good LG) and carbamoyl phosphate (high energy bond)

-product: citrulline

describe step 2 of the urea cycle

-enzyme: synthetase (requires ATP)

-reactants: citrulline and aspartate

-product: argininosuccinate

2 high energy bonds are used ATP -> AMP + PPi

describe step 3 of the urea cycle

-enzyme: argininosuccinase

-reactants: argininosuccinate

-product: arginine and fumarate (can recycle into CAC)

describe step 4 of the urea cycle

-enzyme: arginase

-reactants: arginine

-product: ornithine (recycled back to step 2) and urea (eliminated)

describe step 5 of the urea cycle

steps 3 and 4

3: argininosuccinate

4: arginine

Carbamoyl phosphate and aspartate are part of which steps of urea cycle?

4 ATP

what is the total cost to make urea?

NH4

aspartate

what are the nitrogen sources for the urea cycle?

1.) fumarate is converted to malate to enter the matrix

2.) Asp comes out of the matrix

3.) an aminotransferase is required

what are the 3 key points for how the urea cycle is linked to the CAC?

connects urea cycle with the citric acid cycle

what is the purpose of the aspartate-arginino-succinate shunt shuttle?

-carbon skeletons will be used as fuel

-urea production will increase

-all 5 enzymes in the urea cycle will increase

explain the concepts of long-term regulation during prolonged periods of starvation or if dietary intake is primarily protein:

allosteric activation occurs with increasing concentrations of:

-acetyl CoA and Glutamate

-arginine

explain the concepts of short-term regulation:

there is an NH4+ that needs to be removed

what does it mean if there is an increase in arginine concentration?

N-acetylglutamate synthase (stimulates first step in urea cycle)

what does arginine (increased) activate?

alcaptonuria

benign condition where an individual passes black urine

the absence of homogentisate oxidase

what causes alcaptonuria?

problem: urea synthesis in liver is major route of NH4+ removal and there are no alternate pathways

leads to: hyperamonemia (then leads to coma and irreversible brain damage)

cause: increased conversion of alpha-ketoglutarate to glutamate/glutamine

what is the problem when enzymes in the urea cycle are blocked and what does it lead to and what is possible cause?

providing a surplus of arginine int he diet restricting protein intake

argininosuccinase deficiency can be partly bypassed by...

excess nitrogen accumulates in Gly and Gln

what is carbamoyl phosphate synthetase I deficiency or onithine transcarbamoylase deficiency?

use a natural conjugation pathway to eliminate durgs/biomolecules with a carboxylic acid

-supplement a protein-restricted diet with large amounts of Sodium phenylbutyrate (Buphenyl)

in carbamoyl phosphate synthetase I deficiency and onithine transcarbamoylase deficiency, the problem is to remove Gly and Gln by...

an orphan drug used to treat carbamoyl phosphate synthetase I deficiency or onithine transcarbamoylase deficiency by one round of beta oxidation

what is Sodium Phenylbutyrate (Buphenyl)?

lacks the unpleasant odor of phenylacetate (still has the same bad taste)

what is the advantage of Sodium Phenylbutyrate (Buphenyl)?

disagreeable body odor

What are the adverse effects of Sodium Phenylbutyrate (Buphenyl)?

genetic defect in phenylalanine metabolism, absence/deficiency of phenylalanine hydroxylase

what causes phenylketonuria (severe retardation)?

excess phenylalanine competing with other amino acids for transport across blood brain barrier

-BBB requires lipid solubility and amino acids are water soluble so a transporter is needed

what is the biochemical basis for retardation?

gluconeogenic amino acids

can funnel parts or all of their carbon skeleton to form glucose

-no net input of carbon

-13 amino acids are solely gluconeogenic

ketogenic amino acids

gives rise to ketone bodies and cannot form glucose

-lys and leu are solely this

Ile

Thr

Trp

Phe

Tyr

what amino acids are both keotgenic and glucogenic?

what step they enter

glucogenic amino acids can form less thant 10 ATP in the CAC depending on...

a-ketoglutarate

-gain 3 ATP

succinyl coA

-gain 0.5 ATP

fumarate

-cost 2 ATP

oxaloacetate

-cost 4.5 ATP

pyruvate

-cost 5.5 ATP

what are the five entry points of CAC for gluconeogenic amino acids and what is the gain/cost?

2

-they each contribute 3 carbon atoms

how many gluconeogenic amino acids are needed to form one molecule of glucose?