D-Aminolevulinic acid
Encyclopedia
δ-Aminolevulinic acid is the first compound in the porphyrin
synthesis pathway, the pathway that leads to heme
in mammals and chlorophyll in plants.
In plants, production of δ-ALA is the step on which the speed of synthesis of chlorophyll
is regulated. Plants that are fed by external δ-ALA accumulate toxic amounts of chlorophyll precursor, protochlorophyllide
, indicating that the synthesis of this intermediate is not suppressed anywhere downwards in the chain of reaction. Protochlorophyllide is a strong photosensitizer in plants.
, as well as the α-proteobacteria group of bacteria, it is produced by the enzyme
ALA synthase, from glycine
and succinyl CoA. This reaction is known as the Shemin pathway.
In plants, algae
, bacteria
(except for the α-proteobacteria group) and archaea
, it is produced from glutamic acid
via glutamyl-tRNA and glutamate-1-semialdehyde
. The enzymes involved in this pathway are glutamyl-tRNA synthetase, glutamyl-tRNA reductase
, and glutamate-1-semialdehyde aminotransferase. This pathway is known as the C5 or Beale pathway.
s (protoporphyrin IX) in epithelia
and neoplastic tissue
s, among them malignant glioma
s. It is used to visualise tumorous tissue in neurosurgical
procedures. Studies have shown that the intraoperative use of this guiding method may reduce the tumour residual volume and prolong progression-free survival in patients suffering from this disease.
Aminolevulinic acid is also a photosensitizer for photodynamic therapy
.
(SCC), Bowen's disease
, and other types of cancer.
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
synthesis pathway, the pathway that leads to heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
in mammals and chlorophyll in plants.
In plants, production of δ-ALA is the step on which the speed of synthesis of chlorophyll
Chlorophyll
Chlorophyll is a green pigment found in almost all plants, algae, and cyanobacteria. Its name is derived from the Greek words χλωρος, chloros and φύλλον, phyllon . Chlorophyll is an extremely important biomolecule, critical in photosynthesis, which allows plants to obtain energy from light...
is regulated. Plants that are fed by external δ-ALA accumulate toxic amounts of chlorophyll precursor, protochlorophyllide
Protochlorophyllide
Protochlorophyllide, or monovinyl protochlorophyllide, is an immediate precursor of chlorophyll a that lacks the phytol side-chain of chlorophyll. Unlike chlorophyll, protochlorophyllide is highly fluorescent; mutants that accumulate it glow red if irradiated with blue light...
, indicating that the synthesis of this intermediate is not suppressed anywhere downwards in the chain of reaction. Protochlorophyllide is a strong photosensitizer in plants.
Production
In non-photosynthetic eukaryotes such as animals, insects, fungi, and protozoaProtozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
, as well as the α-proteobacteria group of bacteria, it is produced by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
ALA synthase, from glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
and succinyl CoA. This reaction is known as the Shemin pathway.
In plants, algae
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...
, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
(except for the α-proteobacteria group) and archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
, it is produced from glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
via glutamyl-tRNA and glutamate-1-semialdehyde
Glutamate-1-semialdehyde
This file may be error. The precursor to ornithine and proline is thought to be glutamate-5-semialdehyde. See, for instance, Thomas M. Devlin, Textbook of Biochemistry with Clinical Correlations, Sixth Edition, p. 755 and p. 756 .Glutamate-1-semialdehyde is a molecule formed from...
. The enzymes involved in this pathway are glutamyl-tRNA synthetase, glutamyl-tRNA reductase
Glutamyl-tRNA reductase
A glutamyl-tRNA reductase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are L-glutamate 1-semialdehyde, NADP+, and tRNA, whereas its 3 products are L-glutamyl-tRNA, NADPH, and H+....
, and glutamate-1-semialdehyde aminotransferase. This pathway is known as the C5 or Beale pathway.
Clinical significance
It elicits synthesis and accumulation of fluorescent porphyrinPorphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
s (protoporphyrin IX) in epithelia
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
and neoplastic tissue
Biological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
s, among them malignant glioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
s. It is used to visualise tumorous tissue in neurosurgical
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
procedures. Studies have shown that the intraoperative use of this guiding method may reduce the tumour residual volume and prolong progression-free survival in patients suffering from this disease.
Aminolevulinic acid is also a photosensitizer for photodynamic therapy
Photodynamic therapy
Photodynamic therapy is used clinically to treat a wide range of medical conditions, including malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic...
.
Cancer diagnosis
Photodynamic detection (PDT) is the use of photosensitive drugs with a light source of the right wavelength for the detection of cancer, using fluorescence of the drug. PDT treatment possibilities include those for cancer of the prostate, breast, giant BCC (skin), cervix, recurrent bladder, vulvar, brain (human glioblastoma cells), HPV, lung, stomach, head and neck, penis, and colon, as well as those for leukemia, Barrett's oesophagus, squamous cell carcinomaSquamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
(SCC), Bowen's disease
Bowen's disease
Bowen's disease is a neoplastic skin disease, it can be considered as an early stage or intraepidermal form of squamous cell carcinoma. It was named after Mark Bowen...
, and other types of cancer.
See also
- PorphyrinPorphyrinPorphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...