Metabolism

PW Emery, King’s College London, London, UK

r 2013 Elsevier Ltd. All rights reserved.

Introduction Amino Acid Biosynthesis

The essential (indispensable) amino acids must be supplied in
Amino acids are generated within the body from three dif-
the diet because their carbon skeletons cannot be synthesized
ferent sources. They enter the body from protein in the diet
in the human body, whereas the nonessential amino acids can
and nonessential (dispensable) amino acids are synthesized
be synthesized from common intermediates of the central
from other metabolic intermediates, but by far the largest
metabolic pathways within the cell, i.e., glycolysis, the pentose
quantities of free amino acids arise from the breakdown of
phosphate pathway and the tricarboxylic acid cycle (TCA
tissue proteins. Similarly there are three metabolic fates for
cycle). So long as the keto-analogues are present almost
amino acids. Amino acid disposal is dominated by protein
all amino acids can be generated by the process of transami-
synthesis, but amino acids are also oxidized to carbon dioxide,
nation. The exceptions are threonine and lysine. Threonine
water, and urea or they may be metabolized to other small
is a poor substrate for mammalian transaminase enzymes,
molecules. The pathways involved in each of these processes
whereas the keto-analogue of lysine, a-oxo-e-aminocaproate,
will be considered and this will be followed by a discussion
is unstable and cyclizes spontaneously to pipecolic acid.
of the movement of amino acids between different compart-
ments within the body (Figure 1).
Glutamic Acid, Glutamine, Proline, and Arginine
Glutamic acid is synthesized by transamination of 2-oxoglu-
Amino Acid Supply tarate, a TCA cycle intermediate. This reaction represents the
first stage in the catabolism of many other amino acids, par-
Dietary Intake ticularly the branched chain amino acids. Vitamin B6 is a
cofactor for all transamination (aminotransferase) reactions.
Protein is digested in the stomach by pepsins and in the
Glutamine is made from glutamic acid and ammonium in
small intestine by proteolytic enzymes from the pancreas.
an energy-requiring reaction catalyzed by glutamine synthe-
The products of digestion are mainly small peptides, which
tase. The synthesis of glutamine plays an important role in the
are then taken up by the intestinal epithelium and hydrolyzed
removal of the ammonium formed in peripheral tissues by
to free amino acids. The portal circulation transports these
deamination of amino acids, as it is transported to the liver
amino acids to the liver, where approximately 75% of the
and used for urea synthesis.
amino acids are metabolized. The remaining 25% then enter
Glutamic acid can be phosphorylated to g-glutamyl
the systemic circulation for transport to other tissues.
phosphate by ATP, and this can then be dephosphorylated
to glutamic-g-semialdehyde. This undergoes nonenzymatic
Oxidation cyclization to D1-pyrroline-5-carboxylate, which can then be
to urea
reduced to proline (see Figure 2).
Arginine is made from ornithine via the reactions of the
urea cycle (see Figure 10). Ornithine can theoretically be made
Dietary Amino Tissue by transamination of glutamic-g-semialdehyde, but as men-
Peptides tioned in the previous paragraph this cyclizes spontaneously
protein acids protein
to pyrroline-5-carboxylate. Thus in practice glutamate is first
acetylated by acetyl CoA to N-acetyl glutamate, so that when
this is converted to N-acetyl glutamic-g-semialdehyde the
Conversion to amino group is blocked and cannot cyclize. The N-acetyl
others compounds
glutamic-g-semialdehyde is then transaminated to N-acetyl
Figure 1 Overview of amino acid metabolism. ornithine and this is deacetylated to ornithine (see Figure 2).

Glutamate -Glutamyl Glutamic--semialdehyde Δ1-Pyrroline-5-carboxylate Proline

phosphate

N-Acetyl N-Acetyl N-Acetyl N-Acetyl

-glutamyl phosphate Ornithine
glutamate glutamic--semialdehyde ornithine

Arginine
Figure 2 Synthesis and catabolism of proline and arginine. Solid lines indicate biosynthetic pathways; broken lines indicate catabolic pathways.

72 Encyclopedia of Human Nutrition, Volume 1 http://dx.doi.org/10.1016/B978-0-12-375083-9.00010-6

 Amino Acids: Metabolism 73

Aspartic Acid and Asparagine Phosphoribosylpyrophosphate

Aspartic acid is derived from transamination of oxaloacetic
acid, a TCA cycle intermediate. As with glutamic acid synthesis,
Phosphoribosyl-ATP
this represents a common mechanism for removing amino
groups from many other amino acids. Asparagine is made
from aspartic acid by transfer of the amide group from Phosphoribosyl-AMP
glutamine.

Alanine Phosphoribosylformimino-AIC-RP
Alanine is made by transamination of pyruvic acid, which is
generated by glycolysis.
Phosphoribulosylformimino-AIC-RP

Serine and Glycine

Serine and glycine are readily interconvertible via methylene Imidazole glycerol-phosphate
tetrahydrofolate, which either condenses with a glycine mol-
ecule to yield serine or is cleaved to yield glycine and tetra-
hydrofolate (see Figure 3). However, there are also separate Imidazole acetol-phosphate
biosynthetic pathways for both molecules. Glycine can be
synthesized by transamination of glyoxylate, which arises Histidinol-phosphate
from the pentose phosphate pathway. Serine can be made by
dephosphorylation of 3-phosphoserine, which is made by
sequential dehydrogenation and transamination of 3-phos- Histidinol
phoglycerate, a glycolytic intermediate (see Figure 3).
Histidine
Histidine
Histidine is synthesized by a relatively long pathway, which has
no branch points and does not lead to the formation of any Urocanic acid
other important intermediates. The main precursors are phos-
phoribosyl pyrophosphate and ATP, with the a-amino group
4-Imidazolone-5-propionic acid
arising by transamination from glutamate (see Figure 4).

Cysteine Formiminoglutamic acid

In man and other animals cysteine can only be synthesized
from the essential amino acid methionine. Methionine
reacts with ATP to form S-adenosylmethionine, an important Glutamic acid
methylating agent within the cell. Transfer of the methyl group Figure 4 Synthesis and catabolism of histidine. Solid lines indicate
results in the formation of S-adenosylhomocysteine, which is biosynthetic pathways; broken lines indicate catabolic pathways.
then converted to homocysteine. Homocysteine can condense
with serine to form cystathionine, which is then cleaved by
cystathionase to yield cysteine (see Figure 5).
Methylation
3-Phosphoglycerate S-Adenosylmethionine S-Adenosylhomocysteine

Glyoxylate 3-Hydroxyphosphoglycerate Methionine Homocysteine

THF Glycine THF Methyl-THF

Glycine Methylene THF Serine Methyl Cystathionine

thio--oxobutyrate

Amino-acetone Pyruvate Cysteine

Methyl thiopropionate Methylene THF

2-Oxopropanol 2-Amino-3-oxobutyrate Thiopyruvate

Pyruvate Threonine Pyruvate

Figure 3 Synthesis and catabolism of glycine, serine, and threonine. Figure 5 Synthesis and catabolism of methionine and cysteine.
Solid lines indicate biosynthetic pathways; broken lines indicate Solid lines indicate biosynthetic pathways; broken lines indicate
catabolic pathways. THF, tetrahydrofolate. catabolic pathways. THF, tetrahydrofolate.
74 Amino Acids: Metabolism

An alternative fate for homocysteine is remethylation to oxidation of the amino acid. It is therefore convenient to
methionine. The methyl donor for this reaction can be either consider these metabolic fates together.
methyltetrahydrofolate, in a reaction for which vitamin B12
is a cofactor, or betaine. Remethylation seems to be quite Glycine, Serine, and Threonine
sensitive to folate status, and plasma homocysteine is be- The interconversion of glycine and serine has already been
coming accepted as a biomarker of nutritional status with mentioned (see Figure 3), and this can act as a mechanism for
respect to folate. Homocystinuria is an important inborn error disposal of either amino acid. In quantitative terms, however,
of metabolism that is caused by impaired activity of cysta- the main tendency is for both to be converted to the common
thionine synthetase, the enzyme that catalyzes the conden- intermediate methylene tetrahydrofolate, which acts as a me-
sation of homocysteine with serine. One of the consequences thyl donor in many important biosynthetic reactions in-
of homocystinuria is premature cardiovascular disease. There cluding the conversion of dUMP to dTMP for DNA synthesis.
is now considerable evidence that milder elevations of plasma An alternative pathway for serine catabolism is deamina-
homocysteine, caused by poorly active variants of the methy- tion to pyruvate. However, the Km of this enzyme is relatively
lenetetrahydrofolate reductase enzyme (which is required to high, so the pathway would only operate at high serine con-
make the methyl donor methyltetrahydrofolate) or by low centrations (see Figure 3).
folic acid status may be an important risk factor for cardio- Another pathway of glycine catabolism is by condensation
vascular disease throughout the population. with acetyl CoA to form amino-acetone. This is then transa-
minated and dehydrogenated to yield carbon dioxide and
Tyrosine pyruvate. Amino-acetone is also formed by the NAD-linked
In mammals, including man, tyrosine can only be formed by dehydrogenation of threonine, followed by the spontaneous
hydroxylation of the essential amino acid phenylalanine in a decarboxylation of the unstable intermediate 2-amino-3-oxo-
reaction that utilizes tetrahydrobiopterin as a cofactor. The butyrate, and this appears to be the main pathway of catab-
inborn error of metabolism phenylketonuria is caused by a olism of threonine in mammals (see Figure 3).
failure of the enzyme phenylalanine hydroxylase. Glycine is also an important precursor for several import-
ant larger molecules. Purines are synthesized by a pathway
which begins with the condensation of glycine and phos-
Protein Breakdown phoribosylamine. Porphyrins, including heme, are synthesized
Amino acids are continuously released by the hydrolysis of from glycine and succinyl CoA via d-aminolaevulinic acid.
proteins. This occurs by several different mechanisms. Much Creatine synthesis involves the addition of the guanidino ni-
intracellular proteolysis occurs within lysosomes, which pro- trogen from arginine to glycine. Glycine is also used to con-
vide the acidic environment within which enzymes such as jugate many foreign compounds, allowing them to be excreted
cathepsins operate. However, there are also cytosolic proteo- in the urine. Glycine also conjugates with cholic acid to form
lytic enzymes, which operate at neutral or alkaline pH. These the major bile acid glycocholic acid.
include the enzymes, which hydrolyze proteins bound to
ubiquitin. There are also extracellular proteinases which de- Glutamic Acid, Glutamine, Proline, and Arginine
grade extracellular proteins such as collagen. Glutamic acid can be transaminated to 2-oxoglutarate, which
can enter the TCA cycle. The amino group would be trans-
ferred to aspartate, which would then enter the urea cycle.
Disposal of Amino Acids Alternatively, glutamate can be deaminated by glutamate
dehydrogenase, with the resulting ammonium entering the
Protein Synthesis urea cycle as carbamoyl phosphate. Decarboxylation of glu-
tamate yields g-aminobutyric acid, an important inhibitory
Protein synthesis represents the major route of disposal of neurotransmitter.
amino acids. Amino acids are activated by binding to specific Glutamine is deamidated to glutamic acid in the kidney,
molecules of transfer RNA and assembled by ribosomes into a this process being central to the maintenance of acid–base
sequence that has been specified by messenger RNA, which in balance and the control of urine pH. Glutamine also acts as a
turn has been transcribed from the DNA template. Peptide nitrogen donor in the synthesis of purines and pyrimidines.
bonds are then formed between adjacent amino acids. Once Proline is metabolized by oxidation to glutamic acid,
the polypeptide chain has been completed the subsequent although the enzymes involved are not the same as those
folding, post-translational amino acid modifications and which are responsible for the synthesis of proline from glu-
protein packaging are all determined by the primary sequence tamic acid (see Figure 2).
of amino acids. The rate of protein synthesis is controlled by Arginine is an intermediate of the urea cycle, and is me-
the rate of transcription of specific genes, by the number and tabolized by hydrolysis to ornithine. Ornithine can transfer
state of aggregation of ribosomes and by modulation of the its d-amino group to 2-oxoglutarate, forming glutamic-
rate of initiation of peptide synthesis. g-semialdehyde, which can then be metabolized to glutamate
(see Figure 2). Ornithine can also be decarboxylated to
putrescine, which in turn can be converted to other poly-
Amino Acid Catabolism
amines such as spermidine and spermine.
Many amino acids can be converted to other useful molecules Arginine can also be oxidized to nitric oxide and citrulline.
within the cell and the same pathways may also lead to Nitric oxide appears to be an important cellular signalling
 Amino Acids: Metabolism 75

molecule which has been implicated in numerous functions (see Figure 5). This pathway appears to act mainly as a bio-
including relaxation of the vascular endothelium and cell synthetic pathway for the synthesis of cysteine. There is an
killing by macrophages. In the vascular endothelium nitric alternative pathway for methionine catabolism that involves
oxide is made by two different nitric oxide synthase isozymes, transamination to methyl thio-a-oxobutyrate and thence to
one of which is inducible whereas the other acts constitutively. methyl thiopropionate.
Both require tetrahydrobiopterin as a cofactor. Cysteine can be transaminated to thiopyruvate, which then
undergoes desulphuration to pyruvate and hydrogen sulphide
Aspartic Acid and Asparagine (see Figure 5). Cysteine can also be oxidized to cysteine sul-
Aspartic acid can be transaminated to oxaloacetic acid, a TCA phinic acid, which can then be decarboxylated to hypotaurine,
cycle intermediate. Alternatively, when aspartic acid feeds its which is then oxidized to taurine. High concentrations of
amino group directly into the urea cycle the resulting keto acid taurine are found within most cells of the body, although its
is fumarate, another TCA cycle intermediate. Aspartic acid is role is far from clear. In the liver the main fate of taurine is the
also the starting point for pyrimidine synthesis. Asparagine is production of taurocholic acid, which acts as an emulsifier in
metabolized by deamidation to aspartic acid. the bile.
Another key role for cysteine is in the synthesis of the tri-
peptide glutathione, which is an important intracellular
Lysine
antioxidant.
In mammals lysine is catabolized by condensing with 2-oxo-
glutarate to form saccharopine, which is then converted to
a-aminoadipic acid and glutamate. The a-aminoadipic acid is Leucine, Isoleucine, and Valine
ultimately converted to acetyl CoA. In the brain some lysine The branched chain amino acids are unusual in that the first
is metabolized via a different pathway to pipecolic acid step in their metabolism occurs in muscle rather than liver.
(see Figure 6). Lysine is also the precursor for the synthesis of This step is transamination, producing a-oxoisocaproic acid,
carnitine, which carries long chain fatty acids into the mito- a-oxo-b-methyl valeric acid and a-oxoisovaleric acid. These
chondrion for oxidation. In mammals this process starts with ketoacids are then transported to the liver for decarboxylation
three successive methylations of a lysine residue in a protein. and dehydrogenation. Subsequent catabolism yields acetyl
The trimethyllysine is then released by proteolysis before CoA and acetoacetate in the case of leucine, acetyl CoA, and
undergoing further reactions to form carnitine. propionyl CoA from isoleucine and succinyl CoA from valine
(see Figure 7).
Methionine and Cysteine
The conversion of methionine to cysteine via the so-called
trans-sulphuration pathway has already been mentioned Histidine
The first step in histidine metabolism is deamination to
urocanic acid. Subsequent metabolism of this compound can
Lysine follow several different pathways, but the major pathway is the
2-Oxoglutarate
one which involves formiminoglutamic acid (FIGLU), which
Saccharopine is demethylated by a tetrahydrofolic acid dependent reaction
Glutamate
to glutamic acid (see Figure 4). This forms the basis of the
FIGLU test for folate status. Another physiologically important
2-Aminoadipic semialdehyde
pathway of histidine metabolism is decarboxylation to his-
tamine, for which vitamin B6 is a cofactor.
Pipecolic acid
2-Aminoadipic acid

Phenylalanine and Tyrosine

2-Oxoadipic acid Because mammalian enzymes cannot break open the ben-
zene ring of phenylalanine, the only important pathway for
Glutaryl CoA catabolism of this amino acid is through hydroxylation to
tyrosine. If the phenylalanine hydroxylase enzyme is lacking,
as in phenylketonuria, a high concentration of phenylalanine
Glutaconyl CoA accumulates and it is converted to phenylpyruvate, phenyl-
lactate, and phenylacetate, which are toxic.
Crotonyl CoA Tyrosine is transaminated to p-hydroxyphenylpyruvate,
which is then decarboxylated to homogentisic acid. This is
subsequently metabolized to acetoacetic acid and fumaric acid
3-Hydroxybutyryl CoA (see Figure 8). Small amounts of tyrosine are hydroxylated to
3,4 dihydroxyphenylalanine (DOPA), which is then dec-
Acetoacetyl CoA arboxylated to the catecholamines dopamine, noradrenaline
and adrenaline. DOPA can also be converted to the pigment
melanin. In the thyroid gland protein bound tyrosine is
Acetyl CoA iodinated to the thyroid hormones tri-iodothyronine and
Figure 6 Metabolism of lysine. thyroxine.
76 Amino Acids: Metabolism

Leucine Isoleucine Valine

-Oxoisocaproate -Oxo--methyl valerate -Oxoisovalerate

Isovaleryl CoA -Methylbutyryl CoA Isobutyryl CoA

-Methyl valeryl CoA Tiglyl CoA Methacrylyl CoA

-Methyl crotonyl CoA -Methyl--hydroxybutyryl CoA -Hydroxyisobutyryl CoA

-Methyl glutaconyl CoA -Methylacetoacetyl CoA -Hydroxyisobutyrate

Propionyl CoA
-Hydroxy--methyl glutaryl CoA Acetyl CoA Methylmalonic
semialdehyde
Acetyl CoA
Acetoacetate
Methylmalonyl CoA

Succinyl CoA
Figure 7 Metabolism of the branched-chain amino acids.

Phenylalanine This is the basis of the tryptophan load test for vitamin B6
status.
Tyrosine DOPA A small amount of tryptophan undergoes hydroxylation
to 5-hydroxytryptophan, which is then decarboxylated to the
physiologically active amine 5-hydroxytryptamine (serotonin).
p-Hydroxyphenylpyruvic acid Dopamine

Alanine
Homogentisic acid Noradrenaline Alanine is metabolized by transamination to pyruvate.

Maleyl acetoacetic acid Adrenaline

Acetoacetic acid Urea Cycle

Fumaric acid From the above it can be seen that the metabolism of most
amino acids involves removal of the amino groups by trans-
Figure 8 Metabolism of phenylalanine and tyrosine.
amination. 2-Oxoglutarate is the main acceptor of these
amino groups, being converted to glutamate, which can then
Tryptophan be deaminated to release ammonium. However, ammonium
Tryptophan is oxidized by the hormone-sensitive enzyme is highly toxic and cannot be allowed to accumulate, so it is
tryptophan oxygenase to N-formyl kynurenine, which then converted to urea, which is the form in which most of the
follows a series of steps to yield amino-carboxymuconic nitrogen derived from protein is excreted from the body. Urea
semialdehyde. Most of this undergoes enzymic decarboxyla- is formed in the liver by the cyclic series of reactions shown in
tion, leading ultimately to acetyl CoA. However, a small pro- Figure 10. It can be seen that only one of the nitrogen atoms
portion undergoes nonenzymatic cyclization to quinolic acid, in the urea molecule is actually derived from ammonium, via
which leads to the formation of NAD. This is why excess carbamyl phosphate. The other nitrogen atom comes from
dietary tryptophan can meet the requirement for the vitamin aspartic acid, which is formed by transamination of oxaloa-
niacin (see Figure 9). cetic acid.
One of the steps in the catabolism of tryptophan is The rate of production of urea by the liver is normally
catalyzed by the vitamin B6-dependent enzyme kynureninase. greater than the rate of urea excretion in the urine. This is
If vitamin B6 status is inadequate and a large dose of because some of the urea diffuses into the colon, where it
tryptophan is administered much of the tryptophan will is hydrolyzed to ammonia by bacteria. The ammonia can
be metabolized by an alternative pathway to kynurenic be absorbed and taken up by the liver where it can be re-
and xanthurenic acids, which will be excreted in the urine. incorporated into amino acids, thereby augmenting the net
 Amino Acids: Metabolism 77

Tryptophan Table 1 Amino acid transport systems

System Sodium Preferred amino acids

N-Formyl kynurenine dependence

A Yes Alanine, serine, glycine,

Kynurenine methionine, proline
L No Leucine, isoleucine, valine,
3-Hydroxykynurenine methionine, phenylalanine,
tyrosine, tryptophan, histidine
ASCP Yes Alanine, serine, cysteine, proline
3-Hydroxyanthranilic acid Ly Yes Lysine, histidine, arginine,
ornithine
x
A Yes Aspartate
Amino carboxymuconic x Yes Glutamate
Quinolinic acid G
semialdehyde x No Aspartate, glutamate, cystine
C
yþ Yes Lysine, arginine, histidine
Quinolinic acid b Yes b-Alanine, taurine
2-Aminomuconic
semialdehyde ribonucleotide b0, þ No Lysine, leucine
Gly Yes Glycine, sarcosine
N Yes Histidine, glutamine, asparagine
2-Aminomuconic acid Nicotinic acid Imino Yes Proline
ribonucleotide
-Oxoadipic acid
Glucogenic and Ketogenic Amino Acids
NAD
The carbon skeletons that are left after the amino acids have
been transaminated are converted to common intermediates
Acetyl CoA
of the central metabolic pathways of the cell, so are ultimately
Figure 9 Metabolism of tryptophan. used to provide energy. Clearly, for an adult in energy and
nitrogen balance, energy will be derived from amino acids in
the same proportion as protein is present in the diet. For most
human diets this is in the range 10–15% of energy.
NH4+ CO2 Under certain circumstances, such as starvation, diabetes,
2 × ATP or a high fat diet, the body may need to synthesize glucose
from amino acids rather than oxidizing them directly. Ex-
2 × ADP+Pi periments with diabetic dogs fed on single amino acids have
Carbamyl phosphate shown that most of the amino acids can be converted to
glucose. They are therefore classified as glucogenic. However,
Pi leucine and lysine cannot be converted to glucose, so under
these circumstances they give rise to acetoacetic acid and are
thus classified as ketogenic. This classification can be related to
the catabolic pathways outlined above. The ketogenic amino
Ornithine Citrulline acids are those which are metabolized only to acetyl CoA,
ATP whereas those that are metabolized to pyruvate or TCA cycle
Urea Aspartate intermediates are glucogenic. Tryptophan, phenylalanine,
H2O AMP + PPi tyrosine, isoleucine, methionine, and cysteine are both glu-
cogenic and ketogenic.
Arginine Argininosuccinate

Interorgan Exchange of Amino Acids

Amino Acid Pools

Fumarate
Figure 10 The urea cycle. Free amino acids make up only approximately 2% of the total
amino acid content of the body, the rest being present as
protein. The concentrations of free amino acids are regulated
supply of nonessential amino acids. The colonic bacteria can largely by modulation of their catabolic pathways, though in
also use ammonia to synthesize essential amino acids. There is the case of nonessential amino acids there is also some regu-
evidence that some of these essential amino acids can also lation of the rate at which they are synthesized. There is some
be absorbed and utilized by the human body. However, the evidence that the rates of protein synthesis and degradation
rate at which this happens is clearly not sufficient to meet the are regulated by amino acid supply and that this is another
body’s requirements for essential amino acids. homeostatic mechanism acting to maintain free amino acid
78 Amino Acids: Metabolism

Glucose

Glucose-6-P
Glucose-6-P

Pyruvate
Pyruvate
Amino acids

Urea NH4+ Oxo-acids

Alanine
Alanine

Alanine
Liver Muscle
Figure 11 The glucose–alanine cycle.

concentrations within safe limits. Protein degradation is sup- amino groups from the branched chain amino acids. Muscle
pressed following a meal containing protein, and the rate of also takes up glucose, which is metabolized to supply the
protein synthesis may be increased, so that there is net storage carbon skeletons for alanine and glutamine. Thus there is a
of amino acids as protein. Subsequently, in the postabsorbtive well-recognized glucose–alanine cycle between muscle and
state these changes in the rates of protein synthesis and liver (see Figure 11).
breakdown are reversed, so that there is net release of amino The kidney is a prime site of glutamine deamidation,
acids from protein. In nongrowing adults these changes bal- producing ammonium to maintain acid–base balance and
ance out over a 24-h period, so that there is no net change in regulate the pH of the urine. Glutamine also serves as a sub-
body protein content. The amplitude of these diurnal changes strate for gluconeogenesis in the kidney.
in the rates of protein synthesis and degradation appears to Glutamine is the major energy source for the small intes-
vary in direct proportion to the amount of protein which an tine, and at least part of the glutamine is derived from the
individual habitually consumes. lumen of the gut. Much of the glutamine is metabolized to
Free amino acids are found in all cells of the body and in pyruvate, which is then transaminated and exported to the
extracellular fluid. They are transported between tissues in the liver as alanine. Some glutamine is also converted by the gut to
plasma and transported into cells by a variety of transport citrulline, which then circulates to the kidney to be converted
mechanisms which are relatively specific for particular groups to arginine. Glutamine is also a major energy source for
of amino acids (see Table 1). Amino acids are also present in lymphocytes and monocytes when the immune system is
red blood cells, but their role in interorgan transport appears activated.
to differ from that of plasma. For example, the plasma amino
acid concentration increases as blood traverses the gastro-
intestinal tract after a meal whereas the amino acid content of See also: Amino Acid: Chemistry and Classification. Folic Acid.
blood cells actually decreases. Inborn Errors of Metaboilism: Classification and Biochemical
Aspects; Nutritional Management of Phenylketonuria. Niacin and
Metabolism in Different Organs Pellagra. Protein Digestion and Bioavailability. Protein:
Synthesis and Turnover. Vitamin B6: Physiology
The liver is responsible for most of the deamination of amino
acids, except for the branched chain amino acids, which are
transaminated in muscle. Oxidation of amino acids is one of
the main sources of energy for the liver. The liver is also
Further Reading
the main site of gluconeogenesis, extracting large amounts of
Bender DA (1985) Amino Acid Metabolism, 2nd edn. Chichester: John Wiley and
glutamine and alanine from the plasma for this purpose. The Sons.
liver is the only site of urea synthesis. Finkelstein JD (1990) Methionine metabolism in mammals. Journal of Nutritional
Skeletal and cardiac muscle and adipose tissue are the Biochemistry 1: 228–237.
main sites for transamination of the branched chain amino McCully KS (1996) Homocysteine and vascular disease. Nature Medicine 2:
386–389.
acids, and the resulting ketoacids are transported to the liver Millward DJ (2003) An adaptive metabolic demand model for protein and amino
for oxidation. However, in fasting and diabetes the capacity of acid requirements. British Journal of Nutrition 90: 249–260.
muscle to oxidize branched chain ketoacids increases mark- Waterlow JC and Stephen JML (1981) Nitrogen Metabolism in Man. London:
edly. In the postabsorbtive state there is a net loss of amino Applied Science.
WHO/FAO/UNU (2007) Joint WHO/FAO/UNU expert consultation on protein and
acids from muscle, whereas in the fed state there is net
amino acid requirements in human nutrition. Technical Report Series 935.
uptake, reflecting the changes in net protein deposition and Geneva, Switzerland: WHO.
loss. However, at all times there is net output of alanine and
glutamine from muscle, representing the disposal of the