Entry of Aspartate into the Urea Cycle
• This is the second nitrogen-acquiring reaction
Nitrogen-acquiring reactions in the synthesis of urea. In the reaction catalyzed by argininosuccinate synthetase, the second nitrogen enters from aspartate. Activation of
the ureido oxygen of citrulline in step 1 sets up the addition of aspartate in step 2.
Aspartate –Arginosuccinate Shunt Links Urea Cycle and Citric Acid Cycle
Not All Amino Acids can be Synthesized in Humans
• These amino acids must be obtained as dietary protein
• Consumption of a variety of foods (including vegetarian only diets) well supplies all the essential amino acids
Fate of Individual Amino Acids• Seven to acetyl-CoA
– Leu, Ile, Thr, Lys, Phe, Tyr, Trp
• Six to pyruvate– Ala, Cys, Gly, Ser, Thr, Trp
• Five to -ketoglutarate– Arg, Glu, Gln, His, Pro
• Four to succinyl-CoA– Ile, Met, Thr, Val
• Two to fumarate– Phe, Tyr
• Two to oxaloacetate – Asp, Asn
Summary of Amino Acid Catabolism
Some enzyme cofactors important in one-carbon transfer reactions
Conversions of one-carbon units on tetrahydrofolate
Synthesis of methionine and S-adenosylmethionine in an activated-methyl cycle
Catabolic pathways for alanine, glycine, serine, cysteine,
tryptophan, and threonine
Interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism
Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine.
Tryptophan as precursor
Catabolic pathways for phenylalanine and tyrosine. In humans these amino acids are normally converted to acetoacetyl-CoA and fumarate. Genetic defects in many of
these enzymes cause inheritable human diseases.
Role of tetrahydrobiopterin in the phenylalanine hydroxylase reaction. The H atom shaded pink is transferred directly from C-4 to C-3 in the reaction. This feature,
discovered at the National Institutes of Health, is called the NIH shift.
In PKU, phenylpyruvate accumulates in the
tissues, blood, and urine. The urine may also
contain phenylacetate and phenyllactate.
Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline
Catabolic pathways for methionine,
isoleucine, threonine, and valine.
Catabolic pathways for the three branchedchain amino acids: valine, isoleucine, and leucine. All three pathways occur in extrahepatic tissues and share the first two enzymes, as
shown here. The branched-chain α-keto acid dehydrogenase complex is analogous to the pyruvate and α-ketoglutarate dehydrogenase complexes.This enzyme is defective in people with
maple syrup urine disease.
Catabolic pathway for asparagine and aspartate
Chapter 18: Summary
• Amino acids from protein are an important energy source
in carnivorous animals
• Catabolism of amino acids involves transfer of the amino
group via PLP-dependent aminotransferase to a donor
such as -ketoglutarate to yield L-glutamine
• L-glutamine can be used to synthesize new amino acids,
or it can dispose of excess nitrogen as ammonia
• In most mammals, toxic ammonia is quickly recaptured
into carbamoyl phosphate and passed into the urea cycle
In this chapter, we learned that: