Page last updated: 2024-10-24

NADPH regeneration

Definition

Target type: biologicalprocess

A metabolic process that generates a pool of NADPH by the reduction of NADP+. [GOC:mah]

NADPH regeneration is a crucial process in cellular metabolism, particularly for maintaining reducing power within cells. It's essential for various anabolic pathways like fatty acid biosynthesis, steroid hormone synthesis, and detoxification reactions. The process involves the production of NADPH, a reduced form of nicotinamide adenine dinucleotide phosphate, from its oxidized form, NADP+.

NADPH regeneration occurs through various metabolic pathways, with the most prominent being the **pentose phosphate pathway (PPP)**.

**Here's a step-by-step explanation of the PPP:**

1. **Glucose-6-phosphate (G6P)**, a key intermediate in glucose metabolism, enters the PPP.
2. **G6P dehydrogenase** catalyzes the oxidation of G6P to **6-phosphogluconate** while generating NADPH. This step is the primary source of NADPH in most cells.
3. **6-phosphogluconate dehydrogenase** further oxidizes 6-phosphogluconate to **ribulose-5-phosphate**, another NADPH molecule is produced in this reaction.
4. **Ribulose-5-phosphate** undergoes a series of rearrangements and isomerizations to produce **glyceraldehyde-3-phosphate** and **fructose-6-phosphate**.
5. These products can re-enter glycolysis or be used for biosynthesis pathways.

**Other pathways contribute to NADPH regeneration:**

* **Malic enzyme** catalyzes the oxidative decarboxylation of malate to pyruvate, generating NADPH.
* **Isocitrate dehydrogenase** in the citric acid cycle can use NADP+ as an electron acceptor, producing NADPH.

**The significance of NADPH regeneration lies in its role in:**

* **Reductive biosynthesis:** NADPH provides the reducing power for biosynthetic processes, enabling the formation of complex molecules from simpler precursors.
* **Detoxification:** NADPH fuels enzymes like cytochrome P450 reductase that detoxify harmful compounds like drugs, pollutants, and reactive oxygen species.
* **Protection against oxidative stress:** NADPH is a key component of the glutathione reductase system, which helps maintain the reduced form of glutathione, a critical antioxidant.

In summary, NADPH regeneration is a vital process for cellular function, ensuring the continuous supply of reducing equivalents essential for diverse metabolic reactions.'
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Proteins (1)

ProteinDefinitionTaxonomy
Glucose-6-phosphate 1-dehydrogenaseA glucose-6-phosphate 1-dehydrogenase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P11413]Homo sapiens (human)

Compounds (23)

CompoundDefinitionClassesRoles
furosemidefurosemide : A chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2-ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure.

Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.
chlorobenzoic acid;
furans;
sulfonamide
environmental contaminant;
loop diuretic;
xenobiotic
ketotifenketotifen : An organic heterotricyclic compound that is 4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one which is substituted at position 4 by a 1-methylpiperidin-4-ylidene group. A blocker of histamine H1 receptors with a stabilising action on mast cells, it is used (usually as its hydrogen fumarate salt) for the treatment of asthma, where it may take several weeks to exert its full effect.

Ketotifen: A cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis.
cyclic ketone;
olefinic compound;
organic heterotricyclic compound;
organosulfur heterocyclic compound;
piperidines;
tertiary amino compound
anti-asthmatic drug;
H1-receptor antagonist
thymidinepyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
metabolite;
mouse metabolite
methylprednisolone acetatemethylprednisolone acetate : An acetate ester resulting from the formal condensation of the 21-hydroxy function of 6alpha-methylprednisolone compound with acetic acid.

Methylprednisolone Acetate: Methylprednisolone derivative that is used as an anti-inflammatory agent for the treatment of ALLERGY and ALLERGIC RHINITIS; ASTHMA; and BURSITIS; and for the treatment of ADRENAL INSUFFICIENCY.
11beta-hydroxy steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
3-oxo-Delta(1),Delta(4)-steroid;
acetate ester;
glucocorticoid;
steroid ester;
tertiary alpha-hydroxy ketone
anti-inflammatory drug
androsterone17-oxo steroid;
3alpha-hydroxy steroid;
androstanoid;
C19-steroid
androgen;
anticonvulsant;
human blood serum metabolite;
human metabolite;
human urinary metabolite;
mouse metabolite;
pheromone
dehydroepiandrosteronedehydroepiandrosterone : An androstanoid that is androst-5-ene substituted by a beta-hydroxy group at position 3 and an oxo group at position 17. It is a naturally occurring steroid hormone produced by the adrenal glands.

Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.
17-oxo steroid;
3beta-hydroxy-Delta(5)-steroid;
androstanoid
androgen;
human metabolite;
mouse metabolite
pregnenolone20-oxo steroid;
3beta-hydroxy-Delta(5)-steroid;
C21-steroid
human metabolite;
mouse metabolite
16-bromoepiandrosterone16alpha-bromo-3beta-hydroxy-5alpha-androstan-17-one: a synthetic adrenal hormone that reduced the incidence of tuberculosis and other opportunistic infections in AIDS patients
brexanolonebrexanolone : A 3-hydroxy-5alpha-pregnan-20-one in which the hydroxy group at position 3 has alpha-configuration. It is a metabolite of the sex hormone progesterone and used for the treatment of postpartum depression in women.

brexanolone: a mixture of allopregnanolone and sulfobutylether‐beta‐cyclodextrin for treatment of postpartum depression
3-hydroxy-5alpha-pregnan-20-oneantidepressant;
GABA modulator;
human metabolite;
intravenous anaesthetic;
sedative
tetrahydrodeoxycorticosteronetetrahydrodeoxycorticosterone: RN given refers to (3alpha,5beta)-isomer21-hydroxy steroid
16-hydroxydehydroepiandrosterone16-hydroxydehydroepiandrosterone: RN refers to (3beta,16alpha)-isomer16alpha-hydroxy steroid;
17-oxo steroid;
3beta-hydroxy-Delta(5)-steroid;
androstanoid;
secondary alpha-hydroxy ketone
human metabolite;
mouse metabolite
methotrexatedicarboxylic acid;
monocarboxylic acid amide;
pteridines
abortifacient;
antimetabolite;
antineoplastic agent;
antirheumatic drug;
dermatologic drug;
DNA synthesis inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
immunosuppressive agent
21-hydroxypregnenolone21-hydroxypregnenolone : A hydroxypregnenolone that is pregnenolone which has been substituted by a hydroxy group at position 21.

21-hydroxypregnenolone: RN given refers to (3beta)-isomer;
21-hydroxy steroid;
hydroxypregnenolone;
primary alpha-hydroxy ketone
mouse metabolite
epiandrosteroneepiandrosterone : A 3beta-hydroxy steroid that is (5alpha)-androstane substituted by a beta-hydroxy group at position 3 and an oxo group at position 17.17-oxo steroid;
3beta-hydroxy steroid;
androstanoid
androgen;
human metabolite
paricalcitolhydroxy seco-steroid;
seco-cholestane
antiparathyroid drug
polydatintrans-piceid : A stilbenoid that is trans-resveratrol substituted at position 3 by a beta-D-glucosyl residue.beta-D-glucoside;
monosaccharide derivative;
polyphenol;
stilbenoid
anti-arrhythmia drug;
antioxidant;
geroprotector;
hepatoprotective agent;
metabolite;
nephroprotective agent;
potassium channel modulator
wedelolactonewedelolactone : A member of the class of coumestans that is coumestan with hydroxy substituents as positions 1, 8 and 9 and a methoxy substituent at position 3.

wedelolactone: antihepatotoxic coumestan from Eclipta prostrata and Wedelia calendulacea (both Asteraceae); structure given in first source
aromatic ether;
coumestans;
delta-lactone;
polyphenol
antineoplastic agent;
apoptosis inducer;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
hepatoprotective agent;
metabolite
quercetin
indigo carmine3,5-di-O-(E)-caffeoylquinic acid: from roots of Lychnophora ericoides; structure in first source

3,5-di-O-caffeoyl quinic acid : A carboxylic ester that is the diester obtained by the condensation of the hydroxy groups at positions 3 and 5 of (-)-quinic acid with the carboxy group of trans-caffeic acid. Isolated from Brazilian propolis and Suaeda glauca, it exhibits hepatoprotective and cytotoxic activities.
thiocolchicosidethiocolchicoside: used in combination with glafenine and meprobamate to tranquilize patients undergoing hysterosalpingography; structureglycoside
ml276
mobicmeloxicam : A benzothiazine that is piroxicam in which the pyridin-2-yl group is replaced by a 5-methyl-1,3-thiazol-2-yl group. A non-steroidal anti-inflammatory drug and selective inhibitor of COX-2, it is used particularly for the management of rheumatoid arthritis.

Meloxicam: A benzothiazine and thiazole derivative that acts as a NSAID and cyclooxygenase-2 (COX-2) inhibitor. It is used in the treatment of RHEUMATOID ARTHRITIS; OSTEOARTHRITIS; and ANKYLOSING SPONDYLITIS.
1,3-thiazoles;
benzothiazine;
monocarboxylic acid amide
analgesic;
antirheumatic drug;
cyclooxygenase 2 inhibitor;
non-steroidal anti-inflammatory drug
olanzapineolanzapine : A benzodiazepine that is 10H-thieno[2,3-b][1,5]benzodiazepine substituted by a methyl group at position 2 and a 4-methylpiperazin-1-yl group at position 4.

Olanzapine: A benzodiazepine derivative that binds SEROTONIN RECEPTORS; MUSCARINIC RECEPTORS; HISTAMINE H1 RECEPTORS; ADRENERGIC ALPHA-1 RECEPTORS; and DOPAMINE RECEPTORS. It is an antipsychotic agent used in the treatment of SCHIZOPHRENIA; BIPOLAR DISORDER; and MAJOR DEPRESSIVE DISORDER; it may also reduce nausea and vomiting in patients undergoing chemotherapy.
benzodiazepine;
N-arylpiperazine;
N-methylpiperazine
antiemetic;
dopaminergic antagonist;
histamine antagonist;
muscarinic antagonist;
second generation antipsychotic;
serotonergic antagonist;
serotonin uptake inhibitor