Amino Acid Metabolism Lectures

Amino Acid Degradation

David Nelson For Oct. 29, 2001 Last modified Oct. 26, 2001 3:30 PM Use Garret and Grisham for illustrations Biochemical pathways are all linked together. Fatty acids and cholesterol are made from acetyl CoA generated by the TCA cycle. These carbons are exported to the cytosol as citrate and reconverted to acetyl CoA by ATP citrate lyase. Nucleotides are made starting with amino acids and sugars. To see these interconnections look at Fig. 18.1 p. 567 2nd ed., Fig 17.1, p. 545 1st ed. and Fig. 18.2 p. 568 2nd ed., 17.2, p. 547. 1st ed. Notice the large number of lines in Fig. 17.2 that connect to pyruvate and acetyl CoA, just above the TCA cycle. The degradation of amino acids is also linked to pyruvate, Acetyl CoA and the TCA cycle. in fact: ALL TWENTY AMINO ACIDS ARE BROKEN DOWN INTO TCA CYCLE INTERMEDIATES. (see Fig. 26.41 p. 891 2nd ed., Fig. 26.39, p. 864 1st ed.)

REMOVAL OF AMINO NITROGEN


One of the key steps in amino acid degradation is removal of the alpha amino group.
There are two routes used to remove alpha amino groups.  These are transamination and 
deamination.  Transamination is the most common method.  Nearly all transaminases use 
pyridoxal 5' phosphate as a coenzyme to transfer the amino group.  For a review of 
pyridoxal phosphate and its numerous roles in enzymes see pp. 594-597 2nd ed. p. 480-485 1st 
ed.  For the specific involvment of pyridoxal phosphate in transaminations see Fig. 18.27 p. 
596 2nd ed., Fig. 14.24, p. 483 1st ed.

Before substrate is bound, pyridoxal phosphate exists as a Schiff base with an active site 
lysine.  This is an easily reversible condition and the substrate amino group can compete 
with the active site lysine amino group to form the Schiff base with the pyridoxal 
phosphate.  The Schiff base is hydrolyzed to release the alpha keto backbone of the amino 
acid without the amino group, which remains attached to the pyridoxal phosphate as 
pyridoxamine phosphate.  At this point, another alpha keto acid can react with the 
pyridoxamine to reform the Schiff base.  The enzyme active site lysine can then displace the 
substrate and reform the Schiff base with the pyridoxal phosphate.  The net result is 
transfer of the alpha amino group from an amino acid to an alpha keto acid.  This forms a 
new amino acid and a new alpha keto acid, as in glutamate and oxaloacetate reacting to 
form aspartate and alpha ketoglutarate.  

Transamination moves the amino acid from one carbon skeleton to another.  It does not 
eliminate the amino group as ammonia.  The elimination of the alpha amino group requires 
oxidative deamination.  One enzyme that does this reaction is glutamate dehydrogenase.
The main function of transamination is to funnel amino nitrogen into just a few amino acids 
so enzymes like glutamate dehydrogenase can deaminate them.  This is economical since 
the cell does not have to make 19 different dehydrogenases.  (Remember that proline is an 
imino acid, so it could not be handled in the same way in a deamination reaction).  

The glutamate dehydrogenase enzyme is reversible and it can act in both directions, in 
biosynthesis of glutamate and in the breakdown of glutamate.  (see fig. 26.9 and text on p. 
861-862 2nd ed., fig. 26.7 and text on pp. 832-833 1st ed.)  The oxidative deamination reaction 
uses NAD+, while the synthetic reaction uses NADPH.

In the deamination mode, glutamate is oxidized by a hydride transfer of two electrons and 
one proton to NAD+ (a two electron acceptor) to form NADH.  Ammonia is released when 
a lysine amino group on the enzyme displaces the alpha nitrogen to form a temporary 
covalent adduct with the alpha carbon.  This is hydrolyzed to release alpha ketoglutarate.  

The product, alpha ketoglutarate, can be used in further transamination reactions to feed 
alpha amino groups into this pathway for elimination as ammonia.

What happens to the ammonia?  Ammonia is toxic and must be excreted.  It takes a lot of 
water to eliminate ammonia and keep its concentration relatively low.  This is no problem 
for microorganisms and animals that live in water.  They can eliminate ammonia by 
diffusion.  It is a problem for land animals that need to conserve water.  One solution used 
in many animals including humans is conversion of ammonia to urea.  Urea is a more 
concentrated form of nitrogen, with two nitrogens per molecule and it is less toxic and 
highly water soluble.  Birds are even more water conservative and they excrete uric acid.  
Uric acid is a more concentrated form of nitrogen with four nitrogens per molecule.  It is a 
purine.  Uric acid is not very soluble and in birds, it is excreted as crystals.

THE UREA CYCLE

 (fig 26.23 p. 871 2nd ed., fig. 26.21, p. 844 1st ed)

Urea is formed in the urea cycle.  The last step is cleavage of arginine to form urea and 
ornithine.  If this last step is not taken, then the urea cycle enzymes catalyze the last three 
steps in the synthesis of arginine.  There are only four enzymes in the urea cycle, but in 
mammals, they are located in two different compartments, the cytosol and the mitochondria, 
so two intermediates, ornithine and citrulline, need to be transported back and forth across 
the mitochondrial inner membrane for the cycle to work.  This is done by an ornithine 
mitochondrial carrier and a citrulline mitochondrial carrier, from the same family as the 
ADP/ATP carrier and the phosphate carrier.  The human ornithine carrier called ORNT1 was just 
shown to cause the HHH syndrome (hyperornthinaemia, hyperammonaemia, homocitrullinuria) when 
mutated (Nature Genetics 22, 151-158 1999).  Ammonia and ornithine are elevated because the 
ornithine cannot be transported into the mitochondria, thus ammonia cannot be properly removed.  
The homocitrulline probably comes from carbamylphosphate condensoing with lysine in the absence 
of ornithine in the mitochondria.

In yeast, all the enzymes of the urea cycle are cytosolic. However, ornithine, which is 
needed for the first step in the cycle, is made by a five enzyme pathway in the 
mitochondria, so ornithine must be exchanged across the mitochondrial inner membrane to 
make arginine in the cytosol.  In mammals, ornithine biosynthesis is cytosolic.  Though 
yeast and mammals have some of their enzymes in different compartments, ornithine still 
has to move back and forth across the inner membrane.  

The urea cycle is a means to convert ammonia into urea.  The first reaction in this process is 
not part of the urea cycle, but it produces carbamoyl phosphate that is needed in the first 
step.  The urea cycle cannot go forward without carbamoyl phosphate.  This is made from 
bicarbonate and ammonia by an enzyme called carbamoyl phosphate synthase I.  

In mammals, there are two carbamoyl phosphate synthase genes, CPS I and CPS II.  
CPS I is mitochondrial and is committed to biosynthesis of arginine and the urea cycle.  It 
is the most abundant protein in the mitochondrial matrix, making up 15-26% of the matrix 
protein.  CPS II is cytosolic and committed to the de novo pyrimidine biosynthesis 
pathway.  CPS II is a mulifunctional enzyme with three enzymes coded in one polypeptide 
chain.  These are CPS, aspartate transcarbamoylase (ATCase) and dihydroorotase.  The 
intermediates channel from one enzyme active site to the next without exchanging with the 
cytosolic pool.  

The situation is similar in yeast.  There are still two CPS enzymes, one is committed to the 
urea cycle and arginine biosynthesis, The other is part of a multifunctional enzyme complex 
found in the nucleus called URA2.  URA2 has three enzymatic activities and a non-
functional domain from the fourth enzyme in this pathway.  These are glutamine 
amidotransferase, glutamine dependent carbamoyl phosphate synthetase, aspartate 
transcarbamoylase (ATCase) and a part of dihydroorotase.  This last enzyme is encoded in 
an active form by the URA4 gene.  

The CPS II and the yeast URA2 (for pyrimidine biosynthesis) both get their amino group from 
glutamine rather than ammonia.  

Let us concentrate now on the CPS I that is tied to the urea cycle and arginine biosynthesis.
This enzyme requires bicarbonate, ammonia and 2 ATP to form carbamoyl phosphate (fig. 26.22 p. 
870 2nd ed., fig 26.20, p. 843 1st ed).  The first ATP reacts with bicarbonate to form carbonyl 
phosphate and ADP.  The carbonyl phosphate reacts with ammonia to release phosphate and form 
carbamate.  The carbamate reacts with the second ATP to form carbamoyl phosphate and 
another ADP.  It is expensive to make this compound.  However, a portion of this energy 
is used in the first step of the cycle, when ornithine reacts with carbamoyl phosphate to 
form citrulline catalyzed by ornithine transcarbamylase.  On Sept. 17, 1999 an 18 year old 
patient with a defect in OTCase died as a result of a gene therapy experiment with an 
adenovirus vector delivering OTCase to his liver.  You need to keep in mind when you study 
these pathways that they are not just details to memorize, but they have human consequences.

Citrulline then must be exported from the mitochondrion.  The citrulline molecule has one 
nitrogen that came from ammonia generated by oxidative deamination.  In the next step of 
the cycle, a second nitrogen is donated by aspartate.  Citrulline is activated by addition of 
an AMP group to the oxygen that came from carbamoyl phosphate.  This costs two high 
energy phosphate bonds, since the pyrophosphate PPi is hydrolyzed.  The AMP group is 
displaced by the alpha amino group of aspartate to form agininosuccinate.  This is then 
cleaved by agininosuccinate lyase (or argininiosuccinase) to make arginine and fumarate, a 
TCA cycle intermediate.  Notice that the fumarate cleavage was not done by hydrolysis, 
since that would have given citrulline again and wasted two high energy phosphate 
bonds.  The fumarate can move through the TCA cycle to oxaloacetate where it can be 
transaminated back to aspartate.  This pathway in conjunction with the urea cycle is 
sometimes called the Krebs bicycle. 

The last step in the pathway is cleavage of the arginine by arginase to make urea and 
ornithine.  Notice that ornithine is an amino acid that is like lysine, but it is one methylene 
group shorter.  

There are two arginase genes in humans.  ARG1 codes for a protein in the cytosol and 
accounts for about 98% of liver arginase activity.  The other, ARG2 codes for a protein in 
mitochondria, as outlined in OMIM.  These are expressed in different tissues.  It was 
noticed that researchers working on the Shope papilloma virus had low arginine levels.  
Patients that are defective in arginase have high arginine levels.  Experimental infection of 
fibroblast cell lines of arginase defective patients showed that arginase levels were restored.  
This suggested that patients with this disorder might benefit from infection with this virus.  
This observation was made in 1973, but OMIM does not say that this method was actually 
used on patients.

The urea cycle is mainly located in the liver.  Therefore, ammonia made in other tissues 
must be transported to the liver to be converted to urea.  Ammonia is not transported in the 
blood, rather it is converted to glutamine by glutamine synthase.  Glutamic acid reacts with 
ammonia and ATP to form glutamine.  Once in the liver, glutamine is converted back to 
glutamic acid and ammonia by glutaminase.  

An alternative method to transport amino groups is on alanine.  This can be formed by 
transamination of pyruvate.  Once in the liver, alanine can transaminate alpha ketoglutarate 
to make glutamate and pyruvate.  The glutamate can be oxidatively deaminated by glutamate 
dehydrogenase to form ammonia.  

AMINO ACID DEGRADATION PATHWAYS


There are twenty amino acids from proteins that have to be degraded when they are in 
excess.  Therefore, there are 20 pathways for this degradation.  Do not panic!  All twenty 
amino acids break down into pyruvate, acetyl CoA or four other compounds of the TCA 
cycle.  (see fig. 26.41 p. 891 2nd ed., fig. 26.39, p. 864 1st ed.)  If they go to pyruvate (3 
carbons) or TCA cycle intermediates(4 or 5 carbons), they can be used to make glucose and they 
are called glucogenic.  If they go directly to acetyl CoA they cannot be made into glucose.  
These can be made into ketone bodies, so they are called ketogenic.  Some amino acids are 
broken down into different fragments that are independently ketogenic or glucogenic.  The 
pathways converge to some common routes and they will be considered in groups.

I WILL TEACH THIS MATERIAL AT A MORE DETAILED LEVEL THAN IS 
COVERED IN THE BOOK.  YOU WILL ONLY BE TESTED ON AMINO ACID 
DEGRADATION PATHWAYS COVERED ON PAGES 891-897 2nd ed., Pp.864-869 1st ed.  

THE C3 FAMILY OF AMINO ACIDS


Several amino acids are broken down into pyruvate.  Some only have one part of the 
molecule that is made into pyruvate, like trp.  The other part of trp is converted to alpha 
ketoadipate and this is degraded like a fatty acid.

The simplest member of the C3 amino acids to degrade is alanine.  Transamination between 
alanine and alpha ketoglutarate give pyruvate and glutamate.  Serine and Cysteine are also 
converted to pyruvate.  Serine is converted in one step by serine dehydratase releasing 
pyruvate, ammonia and water. 

Glycine has only two carbon atoms, so in its degradation, it is actually built up to a three 
carbon serine molecule by donation of a hydroxymethyl group by N5 N10 methylene 
tetrahydrofolate.  

Threonine is broken in half, with one half becoming glycine, and the other half reacting 
with CoA to form acetyl CoA.  

Cysteine is modified by different pathways in different 
organisms.  In bacteria H2S can be made.  In mammals the SH group is oxidized by a 
dioxygenase, then the amino group is transaminated to form glutamate and the SO2 group 
is removed to form pyruvate.  The first intermediate is converted to taurine, a component of 
bile acids.

Dioxygenases are frequently used in amino acid degradation.  They incorporate two atoms 
of oxygen into product, as opposed to a monooxygenase that puts one oxygen atom into 
water.  These are often used to break aromatic rings, which is hard to do.  

Trp has a long pathway for degradation.  I will show it to you, but do not memorize it.  
The first step is a dioxygenase reaction to break the five membered ring.  The enzyme is 
called tryptophan dioxygenase.  Defects in this enzyme lead to abnormal levels of serotonin 
which is a neurotransmitter made from trp.  This is thought to be involved in several 
behavioral disorders such as alcoholism, depression and Tourette syndrome.

The third enzyme of trp breakdown is a monooxygenase that oxidizes the remaining 
aromatic ring.  The fourth step releases alanine that goes on to pyruvate.  This make trp a 
member of the C3 amino acids.  The fifth step is another dioxygenase reaction that breaks 
the aromatic ring.  This forms an intermediate in nicotinamide synthesis.  Three more steps 
result in alpha ketoadipate.  The pathway of lysine breakdown also leads to this compound.
We will talk about the futher processing of this compound when we talk about lysine 
degradation.

THE C4 FAMILY OF AMINO ACIDS


The C4 family of amino acids is very small.  It consists of only two amino acids, aspartate 
and asparagine.  As you may suspect, aspartate can be transaminated to form oxaloacetate, 
a four carbon intermediate of the TCA cycle.  Asparagine can be converted to aspartic acid 
by asparaginase.  Aspartate can also be degraded to fumarate in the urea cycle or the purine 
nucleotide cycle, as we saw earlier.  

THE C5 FAMILY OF AMINO ACIDS


All of these amino acids are converted to glutamate and then to alpha ketoglutarate by 
glutamate dehydrogenase.  These include glutamine that can be converted to glutamate by 
glutaminase.  

The glutamate side chain is an acid.  The side chain can also exist as an aldehyde.  The 
compound is then called glutamate gamma semialdehyde.  This is an intermediate in the 
biosynthesis of proline and the degradation of arginine and proline.  Remember arginine is 
cleaved to from ornithine and urea.  Oxidative removal of the delta amino group from 
ornithine to form the aldehyde leads to glutamate gamma semialdehyde.

Proline is converted to the same intermediate by proline oxidase forming a double bond in 
the five membered ring.  The double bond is then hydrolyzed spontaneously to form 
glutamate gamma semialdehyde.

Histidine is converted to glutamate in four steps.  Defects in the first two enzymes in this 
pathway, histidase and urocanase cause histidinemia that leads to mental retardation.

That leaves only seven amino acids.

METHIONINE, ISOLEUCINE, VALINE AND LEUCINE


Three of these: methionine, valine and isoleucine are all converted to propionyl CoA and 
this is made into succinyl CoA (fig. 26.44 p. 895 2nd ed., fig. 26.42, p. 867 1st ed.)  I will 
show you the individual reactions, but you will not be held responsible for these on an exam.  

Isoleucine and valine are branched chain amino acids with the branch on the beta carbon.  
Leucine has the branch on the gamma carbon, so it is handled in a slightly different 
manner.  However, the first three enzymes are the same in all three branched chain amino 
acid degradation pathways.

Isoleucine and valine are first transaminated to form the alpha keto acids.  The next step is 
exactly analogous to pyruvate dehydrogenase conversion of pyruvate to acetyl CoA.  A 
similar enzyme complex does this job and some of the subunits are identical in the pyruvate 
dehydrogenase (PDH) complex and the branch chain keto acid dehydrogenase (BCKDH) 
complex.  A defect in this enzyme causes maple syrup urine disease, where the alpha keto 
acids of the three branch chain amino acids build up in the blood.  The urine smells like 
maple syrup from the alpha keto acid of isoleucine.  (Smell the vial of isoleucine that I pass 
around the classroom.)  One form of this disease is due to a lower affinity of the complex 
for thiamine pyrophosphate, and it can be treated by giving patients thiamine. The two CoA
products are oxidized to form a double bond between the alpha and beta carbons.  Water is 
added across this double bond and then the two pathways diverge slightly.  The isoleucine 
pathway oxidizes the new hydroxyl from the hydration reaction to make a ketone.  The 
valine pathway cannot do this since there is no methyl group attached to the beta carbon.  
Instead, CoA is released.  In the final step, the CoA is added back on the opposite side of 
the molecule to the aldehyde and the carboxyl is released as CO2 to form the propionyl 
CoA.  The isoleucine pathway is simpler, there is just a transfer of the acetyl group to CoA 
to form acetyl CoA and propionyl CoA as the two products.  

The propionyl CoA is converted to succinyl CoA, exactly as seen in beta oxidation of odd 
chain fatty acids, (see fig. 24.19 p. 791 and text on pp. 791-792 2nd ed., see fig. 23.19, p. 
747, text pp. 747-748 1st ed.)  This is a three carbon compound being made into a four carbon 
compound.  The extra carbon is added on as a carboxyl group in a reaction that requires biotin.  
Biotin is usually involved in carboxylation reactions.  The product of the reaction has to 
undergo an unusual carbon skeleton rearrangement that is done by two enzymes, methylmalonyl CoA 
racemase and methylmalonyl CoA mutase.  The mutase enzyme uses coenzyme B12, (5' deoxyadenosyl 
cobalamin).  The cobalamin part is a heme-like corrin ring with cobalt in the center.  The 
sixth ligand to this cobalt is the deoxyadenosyl group, that is covalently bound to the 
cobalt.  This is the only known example of a cobalt carbon bond in biology.  

In the reaction, a proton is abstracted from the methyl group.  Then the carboxyl-CoA 
group migrates to the methyl group.  This results in converting the branched methymalonyl 
CoA into the linear succinyl CoA.

EXCERPT FROM OMIM ON A MURDER MYSTERY


Hoffman (1991) recounted the story of Patricia Stallings who was sentenced to life in 
prison for the presumed murder of her infant son with ethylene glycol, an ingredient of 
antifreeze.[THIS CAUSES ACIDOSIS THAT CAN BE FATAL] While in prison, the 
woman gave birth to a second son, who was found to have methylmalonicacidemia. 
William Sly and James Shoemaker at St. Louis University performed analyses of the first 
son's blood and did not detect ethylene glycol; Piero Rinaldo at Yale University 
demonstrated the biochemical features of methylmalonicacidemia and found no evidence of 
ethylene glycol in the body fluids. All charges against Patricia Stallings were dropped. 
[THIS WAS PROBABLY DUE TO A METHYMALONYL CoA MUTASE DEFECT]
Shoemaker et al. (1992) determined that the gas chromatographic peak that had been 
identified as ethylene glycol by a clinical laboratory was actually due to propionic acid. 
[BREAKDOWN PRODUCT OF PROPIONYL CoA]  Woolf et al. (1992) indicated that 
the opposite situation can obtain: intentional infantile ethylene glycol poisoning being 
misinterpreted as an inborn error of metabolism leading to recurrent infantile metabolic 
acidosis. 
Hoffman, M. : Scientific sleuths solve a murder mystery. Science 254, 931 (1991).

The methionine pathway is notable for its first step that couples methionine to an adenosyl 
group of ATP, releasing PPi and S-adenosylmethionine.  This is used as a methyl donor in 
many reactions.  Once the methyl group is donated, the S-adenosylmethionine cannot be 
directly remade.  Instead it is hydrolyzed to produce homocysteine and adenosine.  The 
homocysteine reacts with serine to form cystathionine, which is deaminated and cleaved to 
form cysteine and alpha ketobutyrate.  This compound is processed by another enzyme 
complex (alpha keto acid dehydrogenase) similar to pyruvate dehydrogenase to make 
propionyl CoA.  

Leucine as was mentioned earlier has a branch at the gamma carbon.  This changes its fate 
from the isoleucine and valine pathways.  The five carbon CoA compound is carboxylated 
to make it a six carbon CoA.  Then water is added across a double bond as was seen for the 
other branched chain amino acids.  Then the six carbon unit is cleaved to make acetyl CoA 
and acetoacetate.  

Now we have lysine, phenylalanine and tyrosine to consider.  

LYSINE


Lysine is degraded in 11 steps.  One important thing to remember is that lysine and 
tryptophan degradation converge at alpha ketoadipate.  A Point of interest is the conversion 
of alpha keto adipate to glutaryl CoA that is done by the same enzyme that acted on alpha 
keto butyrate in the methionine pathway.  This is alpha keto acid dehydrogenase, similar to 
pyruvate dehydrogenase.  Several of the steps downstream from this are just beta oxidation 
of fatty acids.  The last intermediate before production of the final products is HMG CoA 
(hydroxy methylglutaryl CoA).  This was the same in the leucine degradation pathway, and 
the products are the same acetoacetate and acetyl CoA.  

PHENYLALANINE AND TYROSINE


Phenylalanine and tyrosine are very similar in structure and they are both degraded by the 
same pathway.  Phenylalanine is converted to tyrosine by oxidation of the aromatic ring.  
This is not the usual way for tyrosine to be synthesized, but it keeps tyrosine from being an 
essential amino acid in humans.  The oxidation of an aromatic ring is tough chemistry and it 
requires a special coenzyme tetrahydrobiopterin.  The enzyme is called phenylalanine 
hydroxylase.  Deficiency of this enzyme causes phenylketonuria(PKU).  Every baby born 
in the US is tested for PKU, since it leads to mental retardation if a low phenylalanine diet 
is not followed immediately.  Soft drinks that use Aspartame have warnings on the labels 
that the drinks contain phenylalanine.  The result of a lack of the phenyalanine hydroxylase 
is a buildup of phenylpyruvate in the blood.  This is the transaminated product of 
phenylalanine.  Phenylpyruvate is an inhibitor of the brain pyruvate dehydrogenase 
complex, but it is not very effective against the liver PDH.  There is a possibility that 
inhibition of PDH in the brain causes the mental retardation seen in untreated PKU.

The breakdown of tyrosine still requires breakage of the aromatic ring.  This is done by 
two successive dioxygenase reactions.  The first requires ascorbate (vitamin C).  The second 
cleaves the ring of homogentisate to make a product that is isomerized and cleaved to form 
fumarate and acetoacetate.  The enzyme is called homogentisate 1,2 dioxygenase (HGO). 
Failure to cleave homogentisate causes alkaptonuria(AKU).  The Sept. 1996 issue of 
Nature Genetics(available in my lab)  has a two page summary of the history of this 
disease, and an article that shows finally that AKU, the disease, is caused by mutations in 
HGO, the enzyme.  

The story is summarized here.  Homogentisic acid (HGA) causes urine to turn black on 
standing in patients with black urine disease.  This was discovered in 1898 by Archibald 
Garrod.  In 1902 he wrote a paper that showed this disease was an autosomal recessive 
genetic trait, only two years after Mendel's laws of genetic inheritance were rediscovered.  
They had been published in 1859 and lay unknown for 40 years.  In 1908 Garrod 
proposed this disease was an inborn error of metabolism.  It then took 50 years before a 
lowered level of HGO activity could be shown.  Another 36 years went by before the AKU 
trait in humans was mapped to chromosome 3q2.  Workers next cloned an HGO gene from 
a fungus and blast searched the human EST database to find the human homolog.  Then 
they used fluorescence in situ hybridization (FISH) to map the human gene to 3q21-q23, 
the same site as the AKU trait.  Patients with the disease were shown to have mutations in 
the gene and these when expressed in E. coli had no activity, so the genotype matched the 
phenotype and AKU was proven to be caused by mutations in HGO.  It only took 98 years.

Tyrosine is also the direct precursor of dopa, used in making dopamine.  Dopa can also go 
on to form melanin, the pigment in human skin.  The tyrosinase (tyrosine hydroxylase) 
enzymes used in tryosine degradation and dopamine biosynthesis are different enzymes and 
they are found in different tissues.  This is an example of the same product (dopa) being 
used for different purposes in different compartments.  Lack of tyrosinase in melanocytes 
causes albinism, due to the inability to synthesize melanin.

Tyrosine is used in yeast to make a tough polymer found in the cell wall.  Tyrosines are 
linked to form ditryrosine by a cytochrome P450 enzyme.  These dityrosines then get 
incorporated into the cell wall.