UREA CYCLE & Amino Acid Metabolism

Question 1

step 0

Answer 1

CO2 + NH4+ –> carbamoyl phosphate

Question 2

Step 1

Answer 2

carbamoyl phosphate + ornithine —> citrulline

citrulline passes into the cytosol

Question 3

Step 2

Answer 3

citrullyl-AMP intermediate (entry of second amino group) –> arginosuccinate

Question 4

Step 3

Answer 4

arginosuccinate —> arginine + fumarate (enters citric cycle)

Question 5

Step 4

Answer 5

arginine + H2O —> Urea + Ornithine

Hydrolysis produces urea, which regenerates ornithine

Question 6

Nitrate assimilation

Answer 6

Reduction of NO3- to NH4+ occurs in plants, fungi, and bacteria in a two-step process

Question 7

Nitrogen fixation

Answer 7

formation of NH4+ from N2 gas; exclusively a prokaryotic process.

Question 8

IN ANIMALS (Nitrogen)

Answer 8

No nitrogen fixation or assimilation; dependent on plants and microorganisms for the synthesis of organic nitrogenous compounds such as amino acids.

Question 9

Amino Acid Oxidation Occurs when…

Answer 9

• diet rich in proteins and/or ingested amino acids exceeds body’s need for synthesis
• Carnivores derive up to 90% of energy from amino acids
• During starvation, uncontrolled diabetes mellitus or when low carbohydrate diet.

Question 10

Overview of amino acid catabolism in mammals

Answer 10

• Need to deal with NH4+ because it is toxic in mammals
• The amino groups and the carbon skeleton take separate but interconnected pathways

Question 11

Part of the human gastrointenstinal tract

Answer 11

(a) protein cause the release of gastrin which causes parietal cells to secrete HCl and chief cells to secrete pepsinogen

(b) Low pH in intestine secretin released into the blood, which causes the pancreas to release HCO3- into the intestine.

• Exocrine cells release proteases like trypsin into pancreatic duct which leads to the small intestine.

(c) individual Amino Acids absorbed by transporters

Question 12

Acute Pancreatitis

Answer 12

Disease where pancreatic duct is blocked and the proteolytic zymogens are converted to active enzymes that degrade the lining of the pancreas.

Question 13

Where are amino acids metabolized?

Answer 13

The liver
- Amino groups are shuttled to liver in form of GLUTAMINE from most tissues but also as ALANINE from muscle

• Amino groups are converted to urea in mammals for excretion in urine

Question 14

Enzyme-catalyzed Transaminiations

Answer 14

• Alpha-ketoglutarate is the amino group acceptor.
• All aminotransferases have pyridoxal phosphate (PLP) as a cofactor.
• Reaction is readily reversible; happens in liver.
• Collect amino groups in liver from many amino acids as gultamate – a universal amino donor.

Question 15

Pyridoxal phosphate —> the prosthetic group of aminotransderases

Answer 15

• Coenzyme form of pyrido-xine vitamin B6

(a) PLP and its aminated form, pyradoxamine phosphate, tightly bound coenzymes of aminotransferases.

• bound to the enzyme through Schiff-base linkage to a Lys residue at the active site as well as non-covalent interactions

Question 16

How does Glutamate Dehydrogenase catalyze ammonium production (NH4+)?

Answer 16

Through oxidative deamination in mitochondria; glutamate dehydrogenase has the unusual capacity to use either NAD+ or NADP+ as cofactor.

Question 17

How is ammonia transported from other tissues to the liver?

Answer 17

• Form of glutamine, then converted back to glutamate
• Excess ammonia in tissues added to glutamate to form glutamine, process catalyzed by GLUTAMINE SYNTHETASE.
• After transport in bloodstream, glutamine enters the liver and NH4+ is liberated in mitochondria by the enzyme GLUTAMINASE.

Question 18

Glucose-Alanine Cycle

Answer 18

• Alanine serves as carrier of ammonia & carbon skeleton of pyruvate from SKELETAL MUSCLES TO LIVER.

Ammonia is excreted and pyruvate is used to produce GLUCOSE, RETURNED TO THE MUSCLE.

Question 19

Major amino group transfers: Glutamate

Answer 19

Glutamate dehydrogenase in liver mitochondria removes alpha-amino group from glutamate, releases ammonia and regenerates alpha-ketoglutarate

Question 20

Major amino group transfers: Glutamine

Answer 20

Glutamine will be degraded by glutaminase in the mitochondria of liver cell into glutamate and ammonia.

Question 21

Major amino group transfers: Alanine

Answer 21

Degraded in the liver through transamination reaction with alpha-ketoglutarate and this will regenerate pyruvate.

–>Pyruvate can be used to generate glucose which will enter the blood to supply muscle for glycolysis.

Question 22

Urea cycle and reactions that feed amino groups into the cycle

Answer 22

• Takes place in mitochondria and cytosol of liver
• One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix
• The other amino group enters as ASPARTATE, formed in the matrix by transamination of oxaloacetate by glutamate.

Question 23

Energetic Cost of Urea Synthesis

Answer 23

• Four high energy bonds since ATP is converted to AMP
• 4 ATP bonds but get 2.5 ATPs back so about 1.5 ATP/Urea