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δ-Aminolevulinic acid (dALA or δ-ALA or 5ala or 5-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.

Biosynthesis

In non-photosynthetic eukaryotes such as animals, insects, fungi, and protozoa, as well as the Alphaproteobacteria class of bacteria, it is produced by the enzyme ALA synthase, from glycine and succinyl CoA. This reaction is known as the Shemin pathway, which occurs in mitochondria.^[1]

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 2,1-aminomutase. This pathway is known as the C5 or Beale pathway.^[2]^[3] In most plastid-containing species, glutamyl-tRNA is encoded by a plastid gene, and the transcription, as well as the following steps of C5 pathway, take place in plastids.^[4]

Clinical significance

It elicits synthesis and accumulation of fluorescent porphyrins (protoporphyrin IX) in epithelia and neoplastic tissues, among them malignant gliomas. It is used to visualise tumorous tissue in neurosurgical procedures.^[5] 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.^[6]^[7]

Being a precursor of photosensitizer, aminolevulinic acid is also a used as an agent for photodynamic therapy.

Cancer diagnosis

Photodynamic detection is the use of photosensitive drugs with a light source of the right wavelength for the detection of cancer, using fluorescence of the drug.^{[citation needed]}

5-Aminolevulinic acid can be used to visualize bladder cancer.^[8]

Cancer treatment

Photodynamic therapy (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 esophagus, squamous cell carcinoma (SCC), Bowen's disease, and other types of cancer.

References

^ Ajioka, James; Soldati, Dominique, eds. (September 13, 2007). "22". Toxoplasma: Molecular and Cellular Biology (1 ed.). Taylor & Francis. p. 415. ISBN 9781904933342.
^ Beale SI (August 1990). "Biosynthesis of the Tetrapyrrole Pigment Precursor, delta-Aminolevulinic Acid, from Glutamate". Plant Physiol. 93 (4): 1273–9. doi:10.1104/pp.93.4.1273. PMC 1062668. PMID 16667613.
^ Willows, R.D. (2004). "Chlorophylls". In Goodman, Robert M. Encyclopaedia of Plant and Crop Science. Marcel Dekker. pp. 258–262. ISBN 0-8247-4268-0.
^ Biswal, Basanti; Krupinska, Karin; Biswal, Udaya, eds. (2013). "22". Plastid Development in Leaves during Growth and Senescence (Advances in Photosynthesis and Respiration). Dordrecht: Springer. p. 508. ISBN 9789400757233.
^ Eyüpoglu, Ilker Y.; Buchfelder, Michael; Savaskan, Nic E. (2013). "Surgical resection of malignant gliomas—role in optimizing patient outcome". Nature Reviews Neurology 9 (3): 141–51. doi:10.1038/nrneurol.2012.279. PMID 23358480.
^ Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006). "Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial". Lancet Oncol. 7 (5): 392–401. doi:10.1016/S1470-2045(06)70665-9. PMID 16648043.
^ Eyüpoglu, Ilker Y.; Hore, Nirjhar; Savaskan, Nic E.; Grummich, Peter; Roessler, Karl; Buchfelder, Michael; Ganslandt, Oliver (2012). Berger, Mitch, ed. "Improving the Extent of Malignant Glioma Resection by Dual Intraoperative Visualization Approach". PLoS ONE 7 (9): e44885. doi:10.1371/journal.pone.0044885. PMC 3458892. PMID 23049761.
^ "Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer Overview of BCG Immunotherapy".

UpToDate Contents

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1. 先天性および後天性鉄芽球性貧血の原因 causes of congenital and acquired sideroblastic anemias
2. 光線角化症の治療 treatment of actinic keratosis
3. Treatment and prognosis of basal cell carcinoma at low risk of recurrence
4. 鉄芽球性貧血の病態生理 pathophysiology of the sideroblastic anemias
5. ポルフィリン症：概要 porphyrias an overview

English Journal

Effects of sub-lethal and chronic lead concentrations on blood and liver ALA-D activity and hematological parameters in Nile tilapia.

Dos Santos CR1, Cavalcante AL2, Hauser-Davis RA3, Lopes RM4, Da Costa Mattos Rde C2.
Ecotoxicology and environmental safety.Ecotoxicol Environ Saf.2016 Jul;129:250-6. doi: 10.1016/j.ecoenv.2016.03.028. Epub 2016 Apr 4.
Liver and blood δ-aminolevulinic acid dehydratase (ALA-D) inhibition by exposure to sub-lethal lead concentrations over time in Nile tilapia (Oreochromis niloticus) were investigated. All three lead concentrations (1mgkg(-1), 10mgkg(-1) and 100mgkg(-1)) significantly inhibited ALA-D activity in blo
PMID 27054706

Performance, 5-aminolevulinic acid (ALA) yield and microbial population dynamics in a photobioreactor system treating soybean wastewater: Effect of hydraulic retention time (HRT) and organic loading rate (OLR).

Liu S1, Zhang G2, Zhang J1, Li X1, Li J1.
Bioresource technology.Bioresour Technol.2016 Jun;210:146-52. doi: 10.1016/j.biortech.2016.01.030. Epub 2016 Jan 19.
Effects of hydraulic retention time (HRT) and influent organic loading rate (OLR) were investigated in a photobioreactor containing PNSB (Rhodobacter sphaeroides)-chemoheterotrophic bacteria to treat soybean wastewater. Pollutants removal, biomass production and ALA yield in different phases were in
PMID 26818577

Metabolic engineering of Corynebacterium glutamicum for efficient production of 5-aminolevulinic acid.

Feng L1,2,3, Zhang Y1,2,3, Fu J1,2,3, Mao Y1,2,3, Chen T1,2,3, Zhao X1,2,3, Wang Z4,5,6.
Biotechnology and bioengineering.Biotechnol Bioeng.2016 Jun;113(6):1284-93. doi: 10.1002/bit.25886. Epub 2015 Dec 9.
5-Aminolevulinic acid (5-ALA) has recently attracted attention for its potential applications in the fields of medicine and agriculture. In this study, Corynebacterium glutamicum was firstly engineered for 5-ALA production via the C4 pathway. HemA encoding 5-aminolevulinic acid synthase from Rhodoba
PMID 26616115

Japanese Journal

赤芽球特異的5-アミノレブリン酸合成酵素の遺伝子変異と疾患

岩手医学雑誌 67(1), 1-9, 2015-04-01
NAID 110009909093

1P-075 Streptomyces coeruleorbidus由来aminolevulinate aminotransferaseの精製およびキャラクタリゼーション、遺伝子クローニング(酵素学,酵素工学,一般講演)

日本生物工学会大会講演要旨集 66, 36, 2014-08-05
NAID 110009906156

赤芽球5-アミノレブリン酸合成酵素の異常とポルフィリン代謝

ALA-porphyrin science 2(1-2), 19-26, 2013
NAID 40020015163

Related Pictures

★リンクテーブル★

リンク元	「ヘム」「5-アミノレブリン酸」
拡張検索	「5-aminolevulinate dehydratase」「aminolevulinate dehydratase」

「ヘム」

δ-Aminolevulinic acid
Systematic (IUPAC) name
	5-amino-4-oxo-pentanoic acid
Clinical data
Pregnancy	C;
Legal status
Legal status	℞ (Prescription only);
Identifiers
CASRN	106-60-5
ATC code	L01XD04 (WHO)
PubChem	CID 137
IUPHAR/BPS	4784
DrugBank	DB00855
ChemSpider	134
UNII	88755TAZ87
KEGG	D07567
ChEBI	CHEBI:356416
ChEMBL	CHEMBL601
Chemical data
Formula	C5H9NO3
Molar mass	131.13 g/mol
	SMILES O=C(CN)CCC(=O)O ;
	InChI InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9) ; Key:ZGXJTSGNIOSYLO-UHFFFAOYSA-N ;
Physical data
Melting point	118 °C (244 °F)
(verify)

　　[★]

英: heme
同: プロトヘム protoheme、フェロプロトポルフィリンIX ferroprotoporphyrin IX
関: ヘマチン hematin

ポルフィリンと鉄イオンの錯体

生合成

→ポルフィリン

反応場所						酵素	補酵素	酵素阻害物質	酵素の障害による疾患
ミトコンドリア	サクシニルCoA succinyl-CoA	グリシン glycine	5-アミノレブリン酸 aminolevulinic acid aminolevulinate ALA	CoA	CO2	5-アミノレブリン酸シンターゼ ALA synthase	ビタミンB6
細胞質	5-アミノレブリン酸 aminolevulinic acid aminolevulinate ALA	←2分子	ポルホビリノゲン porphobilinogen PBG	2H2O		ALA dehydratase		Pb
細胞質	ポルホビリノゲン porphobilinogen PBG		ヒドロキシメチルビラン	4NH3		ウロポルフィリゲノンIシンターゼ uroporphyrinogen I synthase			急性間欠性ポルフィリン症 acute intermittent porphyria
細胞質	ヒドロキシメチルビラン		ウロポルフィリノゲンIII			ウロポルフィリゲノンIIIシンターゼ uroporphyrinogen III synthase
細胞質	ウロポルフィリノゲンIII		コプロポルフィリノゲンIII	4CO2		ウロポルフィリノゲンデカルボキシラーゼ			晩発性皮膚ポルフィリン症 porphyria cutanea tarda
ミトコンドリア	コプロポルフィリノゲンIII		プロトポルフィリノゲンIX	2CO2		コプロポルフィリノゲンオキシダーゼ
ミトコンドリア	プロトポルフィリノゲンIX		プロトポルフィリンIX			プロトポルフィリノゲンオキシダーゼ
ミトコンドリア	プロトポルフィリンIX	Fe2+	ヘム			フェロケラターゼ		Pb

生合成の場所

哺乳類細胞では、赤血球以外は何処でも行われる(ミトコンドリアを有するなら)
実際には、赤血球前駆細胞(erythroid precursor cell)で85%行われており、残りは肝細胞で行われている。

「5-アミノレブリン酸」

　　[★]

英: 5-aminolevulinate 5-aminolevulinic acid , δ-aminolevulinate δ-aminolevulinic acid δ-ALA, aminolevulinate aminolevulinic acid ALA
同: δ-アミノレブリン酸
関: ALA synthase、レブリン酸

構造式：H₂NCH₂COCH₂CH₂COOH

レブリン酸のδ酸素にアミノ基がついた形

概念

ヘム合成の中間体
ミトコンドリアでサクシニルCoAとグリシンからALA synthaseにより5-アミノレブリン酸が生成する。
ミトコンドリアで作成された5-アミノレブリン酸は細胞質に移動
細胞質の2分子の5-アミノレブリン酸はポルホビリノゲンシンターゼによりポルホビリノゲンを生成する。

「5-aminolevulinate dehydratase」

　　[★] アミノレブリン酸デヒドラターゼ

「aminolevulinate dehydratase」