Amino acids metabolism

‫ المرحلة االولى‬/ ‫ أيه محمد موجر‬: ‫الطالبة‬

Amino acids are produced by digestion of dietary proteins in
the intestines, absorbed through the intestinal epithelial cells, and
enter the blood. Various cells take up these amino acids, which
enter the cellular amino acid pools. Amino acids are used for the
synthesis of proteins and other nitrogen-containing compounds, or
their carbon skeletons are oxidized for energy or used for the
synthesis of glucose during hypoglycemia. The body maintains a
relatively large free amino acid pool in the blood (approximately
35-65 mg/deci Liter), even during fasting; tissues have continuous
access to individual amino acids for the synthesis of proteins and
essential amino acid derivatives, such as neurotransmitters. The
amino acid pool also provides the liver with substrates for
gluconeogenesis and ketogenesis. The free amino acid pool is
derived from dietary amino acids and the proteolysis of body
proteins. All useful nitrogen in the body is derived from amino
acids. All nitrogen-containing compounds of the body are
synthesized from amino acids - cellular proteins, hormones (e.g.,
thyroxine, epinephrine, insulin), neurotransmitters, creatine
phosphate, heme in hemoglobin and cytochromes, melanin, purine
and pyrimidine bases.

Proteolytic enzymes (proteases) degrade dietary proteins into

their constituent amino acids in the stomach and intestine. In the
stomach, pepsin begins the digestion of dietary proteins by
hydrolyzing them to smaller polypeptides. In the intestine,
bicarbonate neutralizes stomach acid, and the pancreas secretes
several inactive proenzymes (zymogens), which, when activated,
collectively digest peptides to single amino acids. Amino acids are
absorbed by intestinal epithelial cells and released into the blood

Amino acids enter cells from the blood principally by Na +-

dependent cotransporters and, to a lesser extent, by facilitated
transporters. The Na+-dependent transport in liver, muscle, and
other tissues allows these cells to concentrate amino acids from
blood. These transport proteins are encoded by different genes and
have different specificities than those encoded by the genes
specifying the luminal membrane amino acid transporters of the
intestinal epithelia. They also differ somewhat between tissues
 A Partial Roadmap For Amino Acid Metabolism
 

SYNTHESIS & DEGRADATION OF AMINO ACIDS

Nonessential Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine

Essential Arginine*, Histidine, Isoleucine, Leucine, Lysine, Methionine*, Phenylalanine*, Threonine, Tryptophan, Valine
  Synthesis of Non-Essential Amino Acids

Arginine is essential in children and adolescents but not in adults who

have completed growth. The sulfer of cysteine is supplied by methionine;
if methionine is limiting, cysteine becomes essential. Tyrosine is
synthesized from phenylalanine; if phenylalanine is limiting, tyrosine
becomes essential.

The liver is the only tissue that has all the pathways of amino acid
synthesis and degradation. During fasting, the carbon skeletons of amino
acids produce glucose, ketone bodies, and CO2; in the fed state the liver
can convert intermediates of amino acid metabolism to triacylglycerols;
the fate of amino acid carbon skeletons, thus, parallels that of glucose and
fatty acids

 Synthesis of the non-essential amino acids:

 Except for the synthesis of tyrosine from phenylalanine,

carbon skeletons of the non-essential amino acids are
produced from intermediates of glycolysis and the TCA
cycle; four (serine, cysteine, glycine, alanine) from
glycolytic intermediates, five (aspartate, asparagine,
 glutamic acid, glutamine, proline) from TCA cycle
intermediates. Histidine is derived from glucose via the
pentose phosphate pathway. Arginine is produced from
ornithine by the urea cycle.

 Nitrogen is supplied as ammonia via transamination, using

glutamic acid as the ammonia donor or, in the case of
glutamic acid synthesis, by the reaction catalyzed by
glutamate dehydrogenase.

 Amino Acid Degradation

Amino acid degradation:

 Most amino acids are deaminated to produce α-keto acids. In

the fed state these α-keto acids can be used to synthesize
triacylglycerols. In the fasted state they produce glucose,
ketone bodies and CO2.

 In the fasted state, amino acids become a major source of

energy. Muscle protein degradation supplies these amino
acids, which the liver uses to synthesize the glucose and
ketone bodies required to sustain life.
  Amino acids are considered to be glucogenic if their carbon
skeletons can be converted, in net amounts, to glucose, and
ketogenic if their carbon skeletons are converted directly to
acetyl CoA or acetoacetate. Some amino acids are both
glucogenic and ketogenic.

 13 amino acids are exclusively glucogenic — alanine,

arginine, aspartic acid, asparagine, cysteine, glutamic
acid, glutamine, glycine, histidine, methionine,
proline, serine, valine

 Two amino acids, leucine and lysine, are exclusively

ketogenic

 Isoleucine, threonine and the aromatic amino acids —

phenylalanine, tryptophan, tyrosine — are both
glucogenic and ketogenic

Hereditary enzyme defects in amino acid metabolism

Since there are so many different pathways for the degradation of
the various amino acids, it is understandable that many of the known
inborn errors of metabolism are related to amino acid metabolism. We
will consider a few examples that affect the pathways discussed here.
Phenylketonuria (PKU)
 homozygous defect of phenylalanine hydroxylase
 affects one in 10,000 newborns among Caucasians; frequency differs
with race
 excess of phenylalanine causes symptoms only after birth;
intrauterine development normal
 cognitive and neurological deficits, probably due to cerebral
serotonin deficit
 treatment with phenylalanine-restricted diet
 some cases are due to reduced affinity of enzyme for cofactor THB,
can be treated with high dosages of THB
As with most genetic enzyme defects, the clinical disease is manifest
only in homozygous individuals. Dietary phenylalanine that is not used
for protein synthesis accumulates and causes toxicity. It appears that the
excess phenylalanine crowds out tryptophan at the L-aromatic amino acid
transporter in brain capillaries. This transporter keeps the brain supplied
with all aromatic amino acids. Since tryptophan is the precursor of the
neurotransmitter serotonin, the competitive inhibition of its transport to
the brain results in a lack of cerebral serotonin , which is believed to
cause the observed deficits in brain function and development.
In addition to phenylalanine itself, some aberrant metabolites
derived from it also occur at increased levels, and the appearance of
ketone derivatives such as phenylpyruvic acid in the urine has given the
disease its name. These metabolites have no proven connection to the
pathogenesis of the disease. The treatment of phenylketonuria is
pretty straightforward: Limitation of dietary phenylalanine. Tyrosine is
sufficiently available in a reasonably protein-rich diet, so that the lack of
its endogenous formation won’t be a problem. The challenge, then, is to
diagnose the disease in newborn kids, before any damage is done.
References
1.  Voet D, Pratt CW, Voet JG (2013) [2012]. Fundamentals of
biochemistry : life at the molecular level (4th ed.). Hoboken, NJ:
John Wiley & Sons. pp. 712–765. 
2. Berg JM, Tymoczko JL, Stryer L (2002). Biochemistry (5th ed.).
New York: W.H. Freeman.
3. Taylor A (February 1993). "Aminopeptidases: structure and
function". FASEB Journal. 7(2): 290–8.
4. William J. Marshall, in Clinical Biochemistry: Metabolic and
Clinical Aspects (Third Edition), 2014