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3'-phosphoadenosine 5'-phosphosulfate metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving 3'-phosphoadenosine 5'-phosphosulfate, a naturally occurring mixed anhydride. It is an intermediate in the formation of a variety of sulfo compounds in biological systems. [ISBN:0198506732]

3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is a key intermediate in the biosynthesis of sulfated molecules, such as glycosaminoglycans, steroids, and proteins. The PAPS metabolic process encompasses a series of enzymatic reactions that generate and utilize PAPS as a sulfur donor.

**1. Sulfate Activation:**
The process begins with the activation of inorganic sulfate (SO42-) to PAPS. This activation is catalyzed by the enzyme ATP sulfurylase, which uses ATP to convert sulfate to adenosine 5'-phosphosulfate (APS). Subsequently, APS kinase further phosphorylates APS, using another molecule of ATP, to produce PAPS.

**2. PAPS as a Sulfur Donor:**
PAPS serves as the universal sulfur donor in sulfation reactions. It is utilized by a variety of sulfotransferases, which are enzymes that catalyze the transfer of the sulfate group from PAPS to a wide range of acceptor molecules. These acceptor molecules include:

* **Glycosaminoglycans:** PAPS is involved in the sulfation of glycosaminoglycans, such as chondroitin sulfate, heparan sulfate, and dermatan sulfate. These sulfated glycosaminoglycans play critical roles in structural support, cell signaling, and tissue development.
* **Steroids:** PAPS is used in the sulfation of steroid hormones, such as estrogen and testosterone. Sulfation of steroids can modulate their activity and influence their metabolism.
* **Proteins:** PAPS is involved in the sulfation of proteins, a post-translational modification that can alter protein function, stability, and localization. Sulfated proteins are involved in diverse biological processes, including signal transduction, cell adhesion, and immune responses.

**3. PAPS Metabolism Regulation:**
The PAPS metabolic process is tightly regulated to maintain appropriate levels of sulfated molecules. The activity of enzymes involved in PAPS biosynthesis, such as ATP sulfurylase and APS kinase, can be modulated by factors such as substrate availability, cellular conditions, and hormonal signaling.

In summary, the 3'-phosphoadenosine 5'-phosphosulfate (PAPS) metabolic process is a crucial pathway for the biosynthesis of a wide range of sulfated molecules that play essential roles in various biological processes.'
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Proteins (4)

ProteinDefinitionTaxonomy
Sulfotransferase 2A1A sulfotransferase 2A1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q06520]Homo sapiens (human)
Sulfotransferase 1A1A sulfotransferase 1A1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P50225]Homo sapiens (human)
Sulfotransferase 1E1A sulfotransferase 1E1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49888]Homo sapiens (human)
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1An ectonucleotide pyrophosphatase/phosphodiesterase family member 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P22413]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
amoxapineamoxapine : A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position.

Amoxapine: The N-demethylated derivative of the antipsychotic agent LOXAPINE that works by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used for the treatment of depression.
dibenzooxazepineadrenergic uptake inhibitor;
antidepressant;
dopaminergic antagonist;
geroprotector;
serotonin uptake inhibitor
protriptylineProtriptyline: Tricyclic antidepressant similar in action and side effects to IMIPRAMINE. It may produce excitation.carbotricyclic compoundantidepressant
ethinyl estradiol17alpha-ethynylestradiol : A 3-hydroxy steroid that is estradiol substituted by a ethynyl group at position 17. It is a xenoestrogen synthesized from estradiol and has been shown to exhibit high estrogenic potency on oral administration.

Ethinyl Estradiol: A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.
17-hydroxy steroid;
3-hydroxy steroid;
terminal acetylenic compound
xenoestrogen
2-naphthol2-naphthol : A naphthol carrying a hydroxy group at position 2.

2-naphthol: RN given refers to parent cpd

naphthols : Any hydroxynaphthalene derivative that has a single hydroxy substituent.
naphtholantinematodal drug;
genotoxin;
human urinary metabolite;
human xenobiotic metabolite;
mouse metabolite;
radical scavenger
5-hydroxyindolehydroxyindoleshuman metabolite
alpha,beta-methyleneadenosine 5'-triphosphatealpha,beta-methyleneadenosine 5'-triphosphate: do not confuse with beta,gamma-methylene ATP; RN given refers to parent cpdnucleoside triphosphate analogue
adenosine 5'-methylenediphosphatenucleoside diphosphate analogue
3'-o-(4-benzoyl)benzoyladenosine 5'-triphosphate3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate: purinergic receptors agonist; structure given in first sourcepurine ribonucleoside triphosphate
methylthio-adp
6-hydroxybenzothiazole
6-hydroxyindole6-hydroxyindole: structure in first source
Reactive blue 2anthraquinone
4-hydroxytoremifene4-hydroxytoremifene: metabolite of toremifene; RN refers to (Z)-isomer; structure in first source
5-hydroxybenzimidazole5-hydroxybenzimidazole : A member of the class of benzimidazoles that is 1H-benzimidazole carrying a single hydroxy substituent at position 5.

5-hydroxybenzimidazole: only base detected in cobamide cpds from methanol-grown Methanosarcina barkeri
benzimidazoles;
phenols
bacterial metabolite;
human metabolite;
rat metabolite
2-methylthio-atp2-methylthio-ATP: purinergic receptors agonist; relaxes mammalian gut preparations; structure given in first source
adenosine 5'-diphosphate 2',3'-dialdehyde
arl-671566-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP: an inhibitor of ecto-ATPase
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole