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26 Cards in this Set

  • Front
  • Back

Recognize the importance of glutamine and alanine as carriers of amino nitrogen.

a. During overnight fast, muscle proteins are degraded to create free amino acids to maintain “amino acid pool”



  • No storage form for AAs, so pool is constantly being turned over ii.
  • AAs sourced from biosynthesis, diet, and body proteins
b. Glutamine and alanine i. both non essential AAs (can be synthesized de novo)

ii. Used as carriers for nitrogen between the liver and kidneys for gluconeogenesis iii. Alanine major gluconeogenic AA

Explain the general rules of biosynthesis for non-essential amino acids.

a. Synthesized from glucose and ammoniab. 2 of the 11 (cysteine and tyrosine) require an essential for synthesis (methionine and phenylalanine respectively)


i. During times of malnutrition (inadequate dietary AA intake) body is most affected by lack of the 9 essential AAs, and inability to synthesize cysteine and tyrosine


ii. Cysteine requires Methionine and Tyrosine requires Phenylalanine

List the amino acids that are essential/non-essential and glucogenic/ketogenic.

a. Essential:


i. phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, leucine, lysine


b. Non-essential:


i. alanine, arginine*, aspartate, asparagine, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine All A’s, All G’s P.S. CysTyr (like sister) ii. Arginine can be synthesized de novo, but called essential because infant synthesis is too slow


c. Ketogenic (produce acetyl CoA, acetoacetate, and/or B-hydroxybutyrate): i. leucine and lysine (LEUCy LYS)


d. Both keto/glucogenic: i. tyrosine, phenylalanine, isoleucine, tryptophan, threonine [ISO (I saw) THREe PHat TYRes on my TRYP to RehoBOTH beach] or [ISO (I’m so) tyred of trying to phart thrillers]


e. Glucogenic (AAs that are converted to TCA intermediates):


i. alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, valine, histidine, methionine From SMD17: AAAAGGG! Can Someone Please Verify His Marriage?


ii. either feed into TCA, or generate glucose

Explain the importance of the enzymatic reaction in amino acid metabolism.

Enzymatic reactions must occur to AAs before they can be used for energy (because they contain N (2 reactions occur to remove the N (Aminotransferase/transaminase rxn, glutamate deH rxn)

For aminotransferase reactions explain: their biochemical importance.


  • Amino acids cannot directly participate in energy metabolism because they contain nitrogen - aminotransferase reactions are the first step in removing nitrogen from amino acids
  • Aminotransferase reactions results in amino groups being transferred to alpha-ketoglutarate forming glutamate
  • The resulting carbon skeletons participate in metabolism by entering TCA or forming ketone bodies

For the oxidative deamination reaction, relate that: 1) glutamate is the only amino acid that undergoes rapid oxidative deamination, 2) the glutamate dehydrogenase enzyme has allosteric activators and inhibitors, and 3) the clinical ramifications of mutations in the glutamate dehydrogenase enzyme.

Genetic mutations in the glutamate dehydrogenase enzyme can cause hyperinsulinism and hyperammonemia

Genetic mutations in the glutamate dehydrogenase enzyme can cause hyperinsulinism and hyperammonemia

Explain the glutamate dehydrogenase cycle and understand the importance of regenerating a-ketoglutarate.

Purpose - take amino group from one amino acid and transfer it to another carbon skeleton, in order to:
Eliminate the amino group and generate energy create a different amino acid

Purpose - take amino group from one amino acid and transfer it to another carbon skeleton, in order to:


Eliminate the amino group and generate energy create a different amino acid

List the reasons why ammonia is neurologically and biochemically toxic.

Free ammonia in the blood is toxic at concentrations greater than 70 μM (20-50 μM normal)


Ammonia has depressant effects on the CNS (similar to barbituates)


Ammonia alters activity of GABA (inhibitory neurotransmitter)


Ammonia decreases activity of TCA cycleAmmonia in the blood results in high levels of glutamine, which is directly toxic to the brain


A failure to generate urea leads to an accumulation of ammonia in the blood (hyperammonemia)


Ammonia is normally rapidly removed from the blood by the liver (glutamine and alanine carry amino nitrogen to the liver)


In the liver, ammonia is removed by the generation of urea

Describe the two ways to eliminate ammonia: 1) through the liver,

Elimination of ammonia through the liver – Urea Cycle


Primary mode of elimination:


Carried out within the cytosol and mitochondrion of liver cells Glutamate dehydrogenase (GDH) converts glutamate to alpha-ketoglutarate and NH4NH4 is converted to urea, which is excreted in urine


Elimination of ammonia through the kidney


Secondary mode of elimination:


In the kidney, glutamine is hydrolyzed by renal glutaminase releasing ammonia to the urineThe excretion of am

Identify the importance of alanine and glutamine in amino nitrogen transport.

Alanine transports 1 Nitrogen and glutamine transports 2.

Amino group from Glutamate + pyruvate = Ala


Glutamine synthase makes glutamine from glutamate.

Diagram the urea cycle including enzymes.

During metabolic acidosis, explain: How the urea cycle is regulated

Explain how the inhibitor of purine catabolism, allopurinol, is used to diagnose carriers of OTCD.


  • Use a single dose of Allopurinol to diagnoseAccumulation of carbamoyl phosphate results in increased de novo synthesis of pyrimidines
  • Allopurinol (normally used to inhibit purine catabolism) inhibits orotate decarboxylase (part of pyrimidine synthesis) which results in increased orotic acid excreted in the urine.
  • Measure levels to see if pyrimidines (orotic acid is a pyrimidine base) are being overproduced in the body due to carbamoyl phosphate accumulation

Explain why the body does not use the kidney for excretion of ammonium ion under normal metabolic conditions.


  • Why doesn’t the body use the kidney for NH4+ excretion under normal conditions?
  • The liver performs functions that are not possible in kidney. The liver regulates the fate of both the ammonium ion and the carbon skeletons produced in AA metabolism.
  • The liver......is responsible for maintaining nitrogen balance...determines the fate of AA (catabolism or anabolism)...is responsible for the synthesis of nitrogen-containing special products

Describe elimination of ammonia through the kidney

Elimination of ammonia through the kidney:





  • Secondary mode of eliminationIn the kidney, glutamine is hydrolyzed by renal glutaminase releasing ammonia to the urine
  • The excretion of ammonia via the kidney is most important during metabolic acidosis to help maintain blood pH

For aminotransferase reactions explain the amino acids that undergo the reaction

Amino Acids that undergo aminotransferase reactions18 out of 20 amino acids undergo transamination reactionsLysine and threonine are exceptionsThe aminotransferase is named from the original acid donor

For aminotransferase reactions explain the requirement for PLP

Requirement for PLP (Vitamin B6)All aminotransferases require PLP coenzymePLP acts as the intermediate by forming Schiff bases

For aminotransferase reactions explain the reason ALT and AST are two of the most important transaminases.

ALT and AST are two of the most important aminotransferasesALT = alanine aminotransferasePresent in almost all tissuesRequires PLPreversible reaction, but during catabolism this enzyme functions to generate glutamate and pyruvateAlanine is the major gluconeogenic amino acidAST = Aspartate aminotransferasePresent in the liver and kidneyRequires PLPReversible reactionAspartate levels are important in liver because aspartate donates one of the two nitrogen atoms in the formation of urea

Diagram all intersections of Glycolysis/TCA cycle and amino acid metabolism

Diagram the rate limiting step of the urea cycle.

Ketogenicvs. Glucogenic amino Acids.



Urea cycle disorders


Effects of Deficient Urea cycle



What are the clinical symptoms of Ammonia accumulation in the brain?



What is the treatment for hyperammonemia?



Name as many UCDs as possible.