Nitrogen Balance, Urea Cycle, and Amino Acid Metabolism

Question 1

Metabolic Relationships of Amino Acids

Answer 1

Question 2

solely ketogenic AAs

Answer 2

Lysine and leucine

Question 3

Factors that affect Nitrogen Balance

• Positive N balance :
• Negative N balance:

Answer 3

• Positive N Balance
  
  • Intake > breakdown
  • growth, pregnancy, recovery from trauma, infection or under-nutrition, insulin and androgen
• Negative N Balance
  
  • Breakdown > intake
  • inadequate protein intake, starvation, a response to trauma or infection, fever, corticosteroid hormones

Question 4

Amino groups are redistributed amoung amino acids by _________

Answer 4

Aminotransferases (also called transaminases).

Aminotransferases catalyze the removal of the amino group from most amino acids (therefore, FIRST step in their catabolic process)

Question 5

Two amino acids that do not uses aminotransferases to catalzye the removal of its amino group

Answer 5

Threonine and lysine lose their amino groups via deamination.

Question 6

Amine groups are transported to the liver on ________

Answer 6

neutral amino acids (primarily glutamine (because it is neutral, easy to pass through cell membranes into the blood stream for transport), and alanine)

These amino acids rearrange in the liver to form glutamate, aspartate, NH3 for Urea cycle

Question 8

__________ is involved in all transamination reactions

Answer 8

Glutamate

Question 9

Transfer of an amino group from an AA to an α-ketoacid for_______, or to an α-ketoacid to form ________. The original AA then becomes an α-ketoacid, while the α-ketoacid becomes an AA.

Answer 9

breakdown; a nonessential AA

Question 10

Aminotransferases require _________as a prosthetic group/cofactor. Reaction involves a ________intermediate

Answer 10

Pyridoxal Phosphate (PLP; functional form of Vit B6); Schiff’s base

Question 11

Aminotransferase Location

Answer 11

in most cells of the body, but predominantly in the liver and heart

Liver damage causes an increase of transaminases released into the bloodstream (diagnostic)

Common examples: SGOT/SGPT

Question 12

Glutamate must be converted to ___________ to be transferred from tissues to liver

Answer 12

Glutamine (Glutamine Synthetase)

Question 13

Glutamine is also a precursor for __________

Answer 13

Asparagine (transferring the amide from glutamine to aspartate by Asparagine Synthetase)

the g-carboxyl group of aspartate must be activated by ATP before the amide group can be transferred (transamidation)

Question 14

Glutamine carries ________ from peripheral tissues to the kidneys

Hydrolytic enzymes remove the amino groups from both glutamine and asparagine

Answer 14

ammonia

*Liver contains both glutamine synthetase and glutaminase but the enzymes are localized in different cellular compartments.

Question 15

In liver both Glutamate and Glutamine enter _______ in liver cells

Answer 15

mitochondria

In liver mitochondria, Glutamate Dehydrogenase releases amino group of glutamate as ammonia (oxidative deamination)

* Ammonia is toxic, this reaction occurs in mitochondria and thereby restricts amm. toxicity

Question 16

In muscle the glucose-alanine cycle: during _________, transport of ammonia as an amine group on alanine to the liver

Answer 16

during heavy exercise

ALT transaminates pyruvate in muscle to alanine

Alanine passes through the blood to liver

Alanine is transformed back to pyruvate in the liver via ALT

Question 17

Answer 17

Question 18

Possible problems when an enzyme is defective

Answer 18

• lack of product
• accumulation of substrate
• conversion of substrate to toxic substances by other enzymes
• gain of function - protein does something it shouldn’t

In an enzymatic defect of the urea cycle, levels of the immediate substrate of the deficient enzyme are elevated in blood and urine.

Question 19

How can one dispose of excess nitrogen (ammonia)?

Answer 19

• Reduction of production of ammonia by gut microflora
  
  • Use antibiotics
  • Acidification of gut e.g. by lactulose. This is only poorly absorbed from the colon, and mostly metabolized by intestinal flora to an acid. The lowered pH converts NH3 to NH4+. Ammonium ion is more readily excreted than ammonia..
• Dialysis
• Give a detoxifying compound……
  
  • (a) benzoate + glycine -> hippurate (benzolglycine) (or Sodium Butyrate)
  • (b)phenylacetate + glutamine -> phenylacetylglutamine
• Strict management of dietary protein intake
• Arginine Supplement: allosteric activation of NAGS will lead to high CPS1 activity resulting in enhanced incorporation of ammonia into the less toxic intermediate, carbamoyl phosphate