Please confirm topic selection

Are you sure you want to trigger topic in your Anconeus AI algorithm?

Updated: Mar 30 2021

Amino Acid Catabolism

4.7

  • star icon star icon star icon
  • star icon star icon star icon
  • star icon star icon star icon
  • star icon star icon star icon
  • star icon star icon star icon

(21)

  • Overview
    • Three possible fates
      • enter citric acid cycle
      • form ketone bodies
      • substrates for gluconeogenesis
    • Urea cycle
      • function
        • degrade excess amino acids and safely remove nitrogen
          • surplus amino acids cannot be stored
        • produce urea
      • pathway
        • aspartate and carbamoyl phosphate provide nitrogens
          • carbamoyl phosphate synthesized from NH4+ + HCO3- + 2 ATP via carbamoyl phosphate synthetase I
            • rate determining step of pathway
            • requires N-acetylglutamate which regulates the cycle
              • only produced when excess amino acids are present
        • nitrogen added from systemic pool via alanine cycle
        • one turn of the cycle:
          • aspartate + NH3 + CO2 + 3 ATP → urea (containing 2N)+ fumarate + 2 ADP + Pi + AMP + PPi + 3 H20
        • connected to citric acid cycle
          • via aspartate-argininosuccinate shunt
            • fumarate of urea cycle → malate of citric acid cycle
            • oxaloacetate of citric acid cycle → aspartate of urea cycle
      • location
        • cellularly
          • formation of carbamoyl phosphate occurs in the mitochondrial matrix
          • addition of aspartate and removal of fumarate and urea occurs in the cytoplasm
        • systemic
          • liver and kidney
      • deficiencies
        • common presentation
          • hyperammonemia + ↑ [glutamine]blood + ↓ blood urea nitrogen (BUN)
          • onset shortly after birth (< 1-3 day)
          • hyperammonemia intoxication presents with
            • cerebral edema, vomiting, hyperventilation, lethargy, blurring vision
            • α-ketoglutarate consumed
              • stops TCA cycle
        • carbamoyl phosphate synthase I creates carbamoyl phosphate
          • AR inheritance pattern
          • orotic aciduria absent
        • ornithine transcarbamoylase forms citrulline from carbamoyl phosphate
          • XR inheritance pattern
          • most common urea cycle disorder
          • orotic aciduria because excess carbamoyl phosphate is shunted into the UMP synthetic pathway in which orotic acid is an intermediate.
        • treatment
          • low protein diet
          • benzoate or phenylbutyrate
            • chelate nitrogen by becoming aminated
    • Ammonia transport
      • function
        • safely move nitrogenous wastes from tissues to kidney and intestine in the form of glutamine
      • pathway
        • ammonia loaded via glutamine synthetase
          • NH3 + glutamate → glutamine
          • occurs in nearly all tissues
        • ammonia unloaded via glutaminase
          • glutamine → NH3 + glutamate
          • specific to kidneys and intestine (and low concentration in liver)
            • induced by acidosis
    • Glucose-alanine cycle
      • function
        • transport pyruvate from muscle to liver for gluconeogenesis
      • pathway
        • involves reversible aminotransferase reactions
          • alanine aminotransferase (ALT)
            • glutamate + pyruvate → α-ketoglutarate + alanine
              • in muscle
            • α-ketoglutarate + alanine → glutamate + pyruvate
              • in liver
            • requires vitamin B6
          • aspartate aminotransferase (AST)
            • glutamate + oxaloacetate → α-ketoglutarate + aspartate
              • in liver
      • relationship between amino acids andα-keto acids
        • alanine - NH3 = pyruvate
        • aspartate - NH3 = oxaloacetate
        • glutamate - NH3 = α-ketoglutarate
    • Defects in specific amino acid catabolism
      • all are part of newborn screening program
      • phenylketonuria (PKU)
        • inability to break down phenylalanine
          • deficient in phenylalanine hydroxylase
          • ↓ tetrahydrobiopterin cofactor
        • presentation
          • ↑ phenylalanine, ↓ tyrosine
            • requires tyrosine supplementation
          • mental retardation
          • microcephaly
          • musty/mousy odor to sweat and urine
        • restriction of phenylalanine in the diet
          • though cannot eliminate as it essential for protein synthesis
          • very strict adherence to diet during pregnancy for a mother with PKU
          • avoid aspartame
      • maple syrup urine disease
        • inability to breakdown branched-chain amino acids (Val, Leu, Ile)
          • deficient in branched-chain ketoacid dehydrogenase
        • presentation
          • infantile onset
            • normal for first week
            • progressive onset of symptoms
          • lethargy
          • weight loss
          • hyper/hypotonia
          • mental retardation
          • urine smells of maple syrup
          • death if dietary intake of Val, Leu, Ile is not restricted
      • alkaptonuria
        • inability to breakdown homogentisic acid (breakdown product of tyrosine and phenylalanine)
          • deficient in homogentisate oxidase
        • presentation
          • arthritis
            • accumulates over years in the cartilage (ochronosis)
            • onset prior to third decade
          • urine that darkens upon sitting in air
          • dark coloration of the sclera
      • Hartnup's disease
        • deficiency of neutral amino acid transporter
          • leads to ↓ tryptophan absorption
        • presentation
          • pellagra
          • result of niacin deficiency (niacin produced from tryptophan)
      • homocystinuria
        • inability to breakdown homocystinuria (methionine degradation pathway)
          • causes
            • cystathionine synthase deficiency
            • ↓ affinity of cystathionine synthase for pyridoxal phosphate (B6)
            • homocysteine methyltransferase deficiency
            • deficiency in folate, B6 or B12 in the diet can produce elevated levels of homocysteine
        • presentation
          • vessel damage
            • DVT
            • atherosclerosis
            • MI before 2nd decade of life
          • similar to Marfan's
            • mental retardation
            • lens dislocations
              • downward
              • as opposed to upward in Marfan syndrome
            • tall with long extremities
          • ↑ homocysteine in the urine
        • treatment varies by cause
          • cystathionine synthase deficiency
            • ↓ intake of Met, ↑ intake of Cys, B12 and folate
          • ↓ affinity of cystathionine synthase for pyridoxal phosphate
            • ↑ intake of B6
      • propionyl-CoA carboxylase/methylmalonyl-CoA deficiency
        • inability to handle Val, Met, Ile, Thr
        • part of propionic acid pathway
        • presentation
          • ketoacidosis
          • propionyl-CoA carboxylase deficiency has ↑ propionic acid, methyl citrate, hydroxypropionic acid
          • methylmalonyl-CoA mutase deficiency has ↑ methylmalonic acid
        • treat by restricting Val, Met, Ile, Thr in the diet
Card
1 of 0
Question
1 of 15
Private Note

Attach Treatment Poll
Treatment poll is required to gain more useful feedback from members.
Please enter Question Text
Please enter at least 2 unique options
Please enter at least 2 unique options
Please enter at least 2 unique options