Entry of Aspartate into the Urea Cycle This is the second nitrogen-acquiring reaction.

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: