OVERVIEW OF AMINO ACID METABOLISM

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OVERVIEW OF AMINO ACID METABOLISM
ENVIRONMENT
ORGANISM
Bio- synthesis
Protein
Ingested protein
2
3
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a
AMINO ACIDS
b
Degradation (required)
c
c
Purines Pyrimidines Porphyrins
Nitrogen
Carbon skeletons
Urea
pyruvate a-ketoglutarate succinyl-CoA fumarate o
xaloacetate
(glucogenic)
(ketogenic)
Used for energy
acetoacetate acetyl CoA
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NITROGEN BALANCE
Nitrogen balance nitrogen ingested -
nitrogen excreted
(primarily as protein) (primarily as urea)
Nitrogen balance 0 (nitrogen equilibrium)
protein synthesis
protein degradation
Positive nitrogen balance
protein synthesis gt protein
degradation
Negative nitrogen balance
protein synthesis lt protein
degradation
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TRANSAMINATION
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UREA CYCLE
mitochondria
cytosol
Function detoxification of ammonia (prevents
hyperammonemia)
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FATE OF THE CARBON SKELETONS
Carbon skeletons are used for energy.
Glucogenic TCA cycle intermediates
or pyruvate (gluconeogensis)
Ketogenic acetyl CoA, acetoacetyl CoA,
or acetoacetate
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Purine and Pyrimidine Metabolism
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Major Bases
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Source of each atom in the purine ring
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Summary and Regulation
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Inhibition of Purine Biosynthesis by the
Antitumor Agent, 6-Mercaptopurine

1. 6-Mercaptopurine is converted to a nucleotide.
2. The nucleotide inhibits purine biosynthesis at
   steps 2, 12a, 12b, and 13a.

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Major Bases
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Sources of the atoms of the pyrimidine ring
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DNA and RNA Degradation
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Salvage Pathway for Purines (90)
Lesch-Nyhan Syndrome
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Degradation of Purines (10)
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Allopurinol Inhibits xanthine oxidase
X
X
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Heme
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Structure
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Porphyrias
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hemoglobin
globin
heme
Fe (reutilized)
degraded (bilirubin)
free amino acids
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HYPERBILIRUBINEMIA
-- elevated bilirubin in serum (above 1 mg/dL)
-- can be conjugated or unconjugated or both
depending on the situation
-- elevated bilirubin can diffuse into tissues,
making them appear yellow (jaundice)
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HYPERBILIRUBINEMIA Clinical Consequences
-- Conjugated hyperbilirubinemia benign
-- Unconjugated hyperbilirubinemia benign at
concentrations lt 25 mg/dL (albumin capacity)
-- At concentrations gt25 mg/dL, unconjugated
bilirubin is free (uncomplexed) and can enter
the brain.
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Causes of JAUNDICE

• Hemolytic anemia
• -- ? destruction of erythrocytes

• Hepatitis or cirrhosis
• -- ? conjugation and excretion of bilirubin

• Bile duct obstruction
• -- conjugated bilirubin not delivered to
  intestine
• it backs up, spills over into the
  blood

• Neonatal physiological jaundice
• -- immature hepatic system of the newborn
• ? uptake, conjugation, excretion of
  bilirubin