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Dr. Walaa AL-Jedda – 2016/2017
Decarboxylation reaction and biogenic amines
Decarboxylation is the reaction by which CO2 is removed from the COOH group of an
amino acid as a result an amine is formed.
The reaction is catalyzed by the enzyme decarboxylase, which requires pyridoxal-P
(B6-PO4) as coenzyme.
Tissues like liver, kidney, brain possess the enzyme decarboxylase and also by
microorganisms of intestinal tract. The enzyme removes CO2 from COOH group and
convert the amino acid to corresponding amine. This is mostly a process confined to
putrefaction in intestines and produces amines. Biogenic amines formed from various
amino acids and their biologic importance are listed in table (27.1).
Some of the important biogenic amines:
1-Tyramine: Decarboxylation of tyrosine forms tyramine. This occurs in the gut
as a result of bacterial action. Also this reaction takes place in kidney. The reaction is
favoured by O2-deficiency. In the presence of sufficient O2, tissue deaminates
tyrosine. Tyramine elevated blood pressure.
2-Tryptamine: Mammalian kidney, liver and bacteria of gut can decarboxylate
the amino acid, tryptophan to form the amine " tryptamine". Tryptamine also elevate
blood pressure. Hydroxylation at 5-position produces 5-OH tryptamine-5-HT
3- Decarboxylation of amino acids Lysine and Arginine:
Lysine and Arginine may undergo decarboxylation to corresponding "diamines" called
"cadaverine" and "putrescine" respectively, which are largely excreted in feces, but are
essentially non-toxic in amounts ordinarily formed.
4-Histamine: Histamine is formed by decarboxylation of amino acid "Histidine"
by the enzyme Histidine decarboxylase or aromatic L-amino acid decarboxylase in
presence of (B6-PO4).
Site of formation:
-Mast cells are the chief source of histamine in the tissues and its about 10% of the
weight of mast cell granules.
-Also produced by gastric mucosa cells and histaminergic neurones of the central
nervous system.
-Basophiles are the chief source of histamine in the circulating cells.
-Also produced in the gut by bacterial decarboxylation of Histidine.
Mechanisms of action and effects: Histamine acts as neurotransmitter,
particularly in the hypothalamus. It acts as an anaphylactic and inflammatory agent on
being released from mast cells in response to antigens.
Histamine markedly depresses blood pressure
vascular collapse.
and large doses may cause extreme
5-γ- Amino butyric acid (GABA):
Formation: Decarboxylation of glutamic acid produces γ- Amino butyric acid
-glutamate α- decarboxylase is the enzyme which catalyzes the reaction,
- it requires(B6-PO4) as coenzyme and Mg++ as cofactor.
Function of GABA:
-GABA is known to serve as a normal regulator of neuronal activity being active as an
inhibitor (pre-synaptic inhibition).
- It is released at the axon terminals of neurons in grey matter and acts as inhibitory
neurotransmitter by enhancing K+ permeability of postsynaptic membrane.
Clinical Aspect:
Vit. B6 deficiency in children may be responsible for some of the cases of infantile
convulsions. B6 – deficiency causes less formation of GABA leading to neuronal
hyper excitability and convulsions.
GABA Shunt:
GABA by its conversion to succinic acid can form a" by-pass" in TCA cycle.
6- Polyamines:
Polyamines are: - Spermidine
- Spermine
Ornithine in addition to its role in urea cycle, serves as the precursor of ubiquitous
mammalian and bacterial polyamines, Spermidine and Spermine. It requires active
methionine. Normal human can synthesize about 0.5 nmol of Spermine /day.
Clinical significance:
1-Increased polyamines excretion has been claimed to characteristic of malignant
disease. Thus excretion has been reported to be increased in leukemia, and in
carcinoma of ovaries, lungs, colon, rectum, prostate, GI tract, kidney, bladder
and testes.
2-The urinary excretion is increased (5 to 10 times) but the excretion fluctuates with the
clinical state and response to treatment. Good correlation has been found between
urinary excretion and clinical course.
3-However, not all patients with malignant diseases exhibit increased excretion of
4-Spermidine is the best" marker" of tumor cell destruction, whereas putrescine is the
best" marker " for cell proliferation.
Amino acid synthesis and degradation:
Unlike fats and carbohydrates, amino acids are not stored by the body, that is, no
protein exist whose sole function it is to maintain a supply of amino acids for future
use. Therefore, amino acids must be obtained from the diet, synthesized denovo, or
produced from normal protein degradation.
- The catabolism of the amino acids found in proteins involves the removal of α-amino
groups, followed by the breakdown of the resulting carbon skeletons.
-These pathways converge to form seven intermediate products: pyruvate,
intermediates of the TCA cycle (oxaloacetate, α-ketoglutarate, fumarate, succinyl
CoA), acetyl CoA and acetoacetyl CoA.
-These products directly enter the pathway of intermediary metabolism, resulting either
in the synthesis of glucose or lipid, or in the production of energy through their
oxidation to CO2 and water by the citric acid cycle.
-Of the 20 amino acids commonly found in proteins, 11 are not essential in the adult diet,
because they can be synthesized in sufficient amounts in the body, from the intermediates
of metabolism or, as in the case of cysteine and tyrosine, from essential amino acids.
-The essential amino acids cannot be synthesized or produced in sufficient amounts by
the body and therefore, must be obtained from the diet in order for normal protein
synthesis to occur.
-Amino acids also can be classified as Glucogenic or Ketogenic based on which of the
seven intermediates are produced during their catabolism.
a. Glucogenic amino acids
-Amino acids whose catabolism's yield pyruvate or one of the intermediates of the
TCA cycle.
-These intermediates are substrates for gluconeogenesis, and therefore, can give rise to
the net formation of glucose or glycogen in the liver and glycogen in the muscle.
b. Ketogenic amino acids
-Amino acids whose catabolism's yield either acetoacetate or one of its precursors
(Acetyl CoA or acetoacetyl CoA).
-Leucine and lysine are the only exclusively ketogenic amino acids.
-These cannot give rise to the net formation of glucose or glycogen in the liver or
glycogen in the muscle.
Synthesis of amino acids
1-Amino acids derived from intermediates of glycolysis
-Glycolytic intermediates 3- phosphpglycerate serves as precursor for serine, glycine,
cysteine, and alanine.
2-Amino acids derived from TCA cycle
a. Oxaloacetate serves as precursor for aspartate and asparagine.
b. α-ketoglutarate serves as precursor for glutamate, glutamine, proline and arginine
3-Tyrosine: the 11th non-essential amino acid is synthesized from the essential amino
acid phenylalanine
Degradation of amino acids
-When the carbon skeletons of amino acids are degraded, the major products are
pyruvate, intermediates of TCA cycle, acetyl-CoA, and acetoacetate.
1.Amino acids that are converted to pyruvate are serine, glycine, cysteine, and alanine.
2.Amino acids that are converted to intermediates of TCA cycle
a- Amino acids that formed α-ketoglutarate are glutamate, glutamine, proline
arginine and histidine.
b- Amino acids that formed succinyl –CoA are threonine, methionine, valine and
c- Amino acids that formed fumarate are phenylalanine, tyrosine and aspartate.
d- Amino acids that formed oxaloacetate are aspartate and asparagines
3.Four amino acids (lysine, threonine, isoleucine and tryptophan) can form acetylCoA.
Phenylalanine and tyrosine form acetoacetate.
Leucine is degraded to form both acetyl-CoA and acetoacetate.