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Amino Acid Metabolism


Amino Acid Metabolism

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									•     C       H        A       P       T         E       R    •       16       •

                  AMINO ACID
Nonessential Amino Acid Synthesis
Essential Amino Acids
Amino Acid Degradation
Generalities of Amino Acid Catabolism
Products of Amino Acid Degradation

•         •   •    •       •       •         •       •   •        •    •       •


    AMINO ACID                         SYNTHETIC ROUTE

    Ala           From Pyruvate by transamination
    Glu           From -Ketoglutarate by transamination
    Asp           From Oxaloacetate by transamination
    Gln           Glu NH 4 ATP           Gln
    Asn           Asp Gln ATP           Asn AMP PPi Glu
    Ser           Glucose    hydroxypyruvate      Ser
                  Glucose    phosphohydroxypyruvate       Ser
    Gly           Ser THfolate      Gly CH2-THfolate
    Arg           Glu    Glu-semialdehyde     ornithine    Arg
    Pro           Glu    Glu-semialdehyde     Pro
    Tyr           Phe    Tyr (phenylalanine hydroxylase, biopterin cofactor)
    Cys           Met    homoCys Ser         cystathionine    Cys

16   Amino Acid Metabolism                                            •   187   •

     The other nine amino acids are essential and must be taken from the
diet. Notice that some of the amino acids require other amino acids for
their synthesis. Exam questions usually center on whether or not an
amino acid is essential and the metabolites that serve as precursors for
specific amino acids.

     His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val

                    Ketogenic: Leu, Lys
                                  Degraded to acetyl-CoA.
                                  Glucose cannot be made from
     Glucogenic and Ketogenic: Ile, Phe, Tyr, Trp
                                  Goes both ways.
                   Glucogenic: Everything else
                                  Degraded to pyruvate or a member
                                  of the TCA cycle
                                  Glucose can be made from these.

     The complete catabolic pathways of the individual amino acids are
a complex set of pathways that are probably not worth remembering in
detail (this is obviously opinion). This doesn’t mean they’re not impor-
tant. In fact, there are diseases that are caused by inherited defects in
most of the pathways. The preceding table is a general guide that shows
where the amino acids go and points out significant intermediates.

     If a vitamin or cofactor is involved in amino acid metabolism, it’s
          most likely pyridoxal phosphate (B6), unless it involves serine,
          and then it’s B6 and folic acid.
     Nitrogen is dumped into the urea cycle by transamination to make
          Asp or Glu or by deamination to make ammonia.
•   188   •                                       Basic Concepts in Biochemistry

     Ala to pyruvate by transamination
     Arg to urea and glutamate
     Asp to oxaloacetate by transamination or to fumarate via urea cycle
     Asn to Asp
     Cys carbon to pyruvate, sulfur to sulfate
     Glu to -ketoglutarate by transamination, then to glucose
     Gln to glutamate by hydrolysis
     Gly to glyoxylate or serine
     His to glutamate and one-carbon pool
     Met to propionyl-CoA via homocysteine        cystathionine
     Pro to glutamate
     Ser to glycine and CH2THfolate
     Thr to propionyl-CoA through ketobutyrate
     Val to propionyl-CoA through transamination, decarboxylation, and
           a bunch of rearrangements
     Leu to acetoacetate and acetyl-CoA through transamination, decar-
           boxylation, and a bunch of rearrangements
     Ile to propionyl-CoA through transamination, decarboxylation, and
           a bunch of rearrangements
     Phe to Tyr, then to acetoacetate and fumarate
     Tyr to acetoacetate and fumarate
     Try to acetyl-CoA via ring oxidation and cleavage to ketoadipate
     Lys to acetyl-CoA via transamination and deamination to ketoadi-

     The nitrogen contained in the amino acids is usually disposed of
through the urea cycle. One of the early, if not the first, steps in amino
acid catabolism involves a transamination using oxaloacetate or -
ketoglutarate as the amino-group acceptor. This converts the amino acid
into a 2-keto acid, which can then be metabolized further.

      R—CH(NH 3)CO 2        oxaloacetate ∆ R—(C“O)CO 2                Asp

     These enzymes invariably involve a cofactor, pyridoxal phosphate
(vitamin B6). In addition, pyridoxal phosphate is also required for most
decarboxylations, racemizations, or elimination reactions in which an
amino acid is a substrate. Pyridoxal phosphate is not involved in decar-
boxylations in which the substrate is not an amino acid. So if a question
16   Amino Acid Metabolism                                        •   189   •

asks something about an amino acid and a vitamin, the answer will most
likely be pyridoxal phosphate. There are a couple of exceptions in which
pyridoxal phosphate may not be the answer to a vitamins-amino acid
question. If the amino acid is serine, then the answer might also include
folic acid (the reaction here is the conversion of serine to glycine with
the formation of methylene tetrahydrofolic acid–see the section in Chap.
21 on one-carbon metabolism). The other place you might see a vitamin
other than pyridoxal phosphate is in the metabolism of propionyl-CoA,
a product of the catabolism of some amino acids. In this case, the vita-
min may be B12 (the conversion of methylmalonyl-CoA to succinyl-
CoA—see “ -Oxidation Odd-Chain-Fatty Acids” in Chap. 13).
     The nitrogen from the amino groups of most amino acids is transam-
inated into glutamate or aspartate at some point in the degradative
scheme. This nitrogen enters the urea cycle as glutamate, which is reduc-
tively deaminated by glutamate dehydrogenase to yield ammonia or by
the reaction of aspartate with citrulline to give argininosuccinate (urea

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