General Information:

Id: 6,492
Diseases: Metabolic
Mammalia
review
Reference: Quiroz JA et al.(2004) Molecular effects of lithium Mol. Interv. 5: 259-272 [PMID: 15471909]

Interaction Information:

Comment Lithium inhibits some enzymes through competition for Magnesium as a cofactor, since lithium has a ionic radius that is similar to that of magnesium.
Formal Description
Interaction-ID: 61634

drug/chemical compound

Lithium

affects_quantity of

drug/chemical compound

Mg2+

Drugbank entries Show/Hide entries for Lithium
Comment Lithium inhibits inositol polyphosphate 1-phosphatase (IPPase), inositol monophosphate phosphatase (IMPase), fructose 1,6-bisphosphatase (FBPase), and bisphosphate nucleotidase (BPNase). All these enzymes contain a conserved amino acid sequence motif, Asp-Pro-(Ile or Leu)-Asp-(Gly or Ser)-(Thr or Ser), and have a common core tertiary structure that binds metal ions, usually Mg2+.
Formal Description
Interaction-ID: 61636

drug/chemical compound

Lithium

decreases_activity of

gene/protein

INPP1

Drugbank entries Show/Hide entries for Lithium or INPP1
Comment Lithium inhibits inositol polyphosphate 1-phosphatase (IPPase), inositol monophosphate phosphatase (IMPase), fructose 1,6-bisphosphatase (FBPase), and bisphosphate nucleotidase (BPNase). All these enzymes contain a conserved amino acid sequence motif, Asp-Pro-(Ile or Leu)-Asp-(Gly or Ser)-(Thr or Ser), and have a common core tertiary structure that binds metal ions, usually Mg2+.
Formal Description
Interaction-ID: 61637

drug/chemical compound

Lithium

decreases_activity of

gene/protein

IMPase

Drugbank entries Show/Hide entries for Lithium
Comment Lithium inhibits inositol polyphosphate 1-phosphatase (IPPase), inositol monophosphate phosphatase (IMPase), fructose 1,6-bisphosphatase (FBPase), and bisphosphate nucleotidase (BPNase). All these enzymes contain a conserved amino acid sequence motif, Asp-Pro-(Ile or Leu)-Asp-(Gly or Ser)-(Thr or Ser), and have a common core tertiary structure that binds metal ions, usually Mg2+.
Formal Description
Interaction-ID: 61638

drug/chemical compound

Lithium

decreases_activity of

gene/protein

FBP

Drugbank entries Show/Hide entries for Lithium
Comment Lithium inhibits inositol polyphosphate 1-phosphatase (IPPase), inositol monophosphate phosphatase (IMPase), fructose 1,6-bisphosphatase (FBPase), and bisphosphate nucleotidase (BPNase). All these enzymes contain a conserved amino acid sequence motif, Asp-Pro-(Ile or Leu)-Asp-(Gly or Ser)-(Thr or Ser), and have a common core tertiary structure that binds metal ions, usually Mg2+.
Formal Description
Interaction-ID: 61639

drug/chemical compound

Lithium

decreases_activity of

gene/protein

BPNT1

Drugbank entries Show/Hide entries for Lithium
Comment Lithium inhibits the metabolic enzymes phosphoglucomutase and glycogen synthase kinase-3.
Formal Description
Interaction-ID: 61640

drug/chemical compound

Lithium

decreases_activity of

gene/protein

PGM

Drugbank entries Show/Hide entries for Lithium
Comment Lithium inhibits the metabolic enzymes phosphoglucomutase and glycogen synthase kinase-3 beta.
Formal Description
Interaction-ID: 61659

drug/chemical compound

Lithium

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for Lithium or GSK3B
Comment IMPase and IPPase are enzymes involved in recycling and de novo synthesis of inositol, which is a necessary component of the phosphoinositol signaling pathway. Lithium inhibits both enzymes which results in a decrease of free inositol.
Formal Description
Interaction-ID: 61660

gene/protein

IMPase

increases_quantity of

drug/chemical compound

Inositol

Comment IMPase and IPPase are enzymes involved in recycling and de novo synthesis of inositol, which is a necessary component of the phosphoinositol signaling pathway.
Formal Description
Interaction-ID: 61661

gene/protein

IMPase

increases_activity of

Comment IMPase and IPPase are enzymes involved in recycling and de novo synthesis of inositol, which is a necessary component of the phosphoinositol signaling pathway.
Formal Description
Interaction-ID: 61662

gene/protein

INPP1

increases_activity of

Drugbank entries Show/Hide entries for INPP1
Comment IMPase and IPPase are enzymes involved in recycling and de novo synthesis of inositol, which is a necessary component of the phosphoinositol signaling pathway.
Formal Description
Interaction-ID: 61663

gene/protein

INPP1

increases_quantity of

drug/chemical compound

Inositol

Drugbank entries Show/Hide entries for INPP1
Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate.
Formal Description
Interaction-ID: 61664

drug/chemical compound

Inositol

increases_quantity of

Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate.
Formal Description
Interaction-ID: 61665

gene/protein

PLC

decreases_quantity of

Drugbank entries Show/Hide entries for PLC
Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate.
Formal Description
Interaction-ID: 61666

gene/protein

PLC

increases_quantity of

drug/chemical compound

Diacylglycerol

Drugbank entries Show/Hide entries for PLC
Comment IMPase and IPPase are enzymes involved in recycling and de novo synthesis of inositol, which is a necessary component of the phosphoinositol signaling pathway. Lithium inhibits both enzymes which results in a decrease of myo-inositol and an accumulation of inositol-1-monophosphate.
Formal Description
Interaction-ID: 61667

drug/chemical compound

Lithium

decreases_quantity of

drug/chemical compound

Inositol

Drugbank entries Show/Hide entries for Lithium
Comment Fructose 1,6-bisphosphatase (FBPase) is a regulator of gluconeogenesis.
Formal Description
Interaction-ID: 61706

gene/protein

FBP

increases_activity of

process

gluconeogenesis

Comment Bisphosphate 3'-nucleotidase 1 (BPNT1) hydrolyzes inositol-1,4-bisphosphate. This suggests that BPNT1 is involved in inositol recycling.
Formal Description
Interaction-ID: 61708

gene/protein

BPNT1

affects_quantity of

drug/chemical compound

Inositol

Comment Bisphosphate 3'-nucleotidase 1 (BPNT1) acts on bisphosphorylated nucleotides such as 3'-phosphoadenosine 5'-phosphate (PAP), where it removes the 3'-phosphate to form adenosine 5'-phosphate (AMP).
Formal Description
Interaction-ID: 61709

gene/protein

BPNT1

decreases_quantity of

drug/chemical compound

Adenosine 3',5'-bisphosphate

Comment Bisphosphate 3'-nucleotidase 1 (BPNT1) acts on bisphosphorylated nucleotides such as 3'-phosphoadenosine 5'-phosphate (PAP), where it removes the 3'-phosphate to form adenosine 5'-phosphate (AMP).
Formal Description
Interaction-ID: 61710

gene/protein

BPNT1

increases_quantity of

drug/chemical compound

AMP

Comment Bisphosphate 3'-nucleotidase 1 (BPNT1) acts on bisphosphorylated nucleotides such as 3'-phosphoadenosine 5'-phosphate (PAP), where it removes the 3'-phosphate to form adenosine 5'-phosphate (AMP).
Formal Description
Interaction-ID: 61711

gene/protein

BPNT1

increases_activity of

Comment Phosphoglucomutase (PGM) catalyzes the formation of glucose 1-phosphate from glucose 6-phosphate during glycogenolysis.
Formal Description
Interaction-ID: 61729

gene/protein

PGM

increases_activity of

process

gluconeogenesis

Comment BDNF levels increases in the brains of rats treated chronically with lithium.
Formal Description
Interaction-ID: 61742

drug/chemical compound

Lithium

increases_quantity of

gene/protein

BDNF

in the brain; via inducing cAMP-mediated signaling leading to activation of CREB-induced gene transcription
Drugbank entries Show/Hide entries for Lithium
Comment Lithium activates the ERK/MAP kinase cascade in human neuroblastoma SH-SY5Y cells.
Formal Description
Interaction-ID: 61770

drug/chemical compound

Lithium

increases_activity of

process

MAPK cascade

in human neuroblastoma SH-SY5Y cells and in limbic areas of rat brain
Drugbank entries Show/Hide entries for Lithium
Comment Addition of lithium produces an increase in the activation of ribosomal S6 kinase and CREB.
Formal Description
Interaction-ID: 61772

drug/chemical compound

Lithium

increases_activity of

gene/protein

RPS6K

Drugbank entries Show/Hide entries for Lithium
Comment Addition of lithium produces an increase in the activation of ribosomal S6 kinase and CREB. CREB plays a major role in long-term neuroplasticity.
Formal Description
Interaction-ID: 61773

drug/chemical compound

Lithium

increases_activity of

gene/protein

CREB1

via inducing cAMP-mediated signaling and MAPK/ERK cascade
Drugbank entries Show/Hide entries for Lithium or CREB1
Comment Ribosomal S6 kinase is a downstream target of the MAP kinase cascade. Activated ribosomal S6 kinase phosphorylates CREB.
Formal Description
Interaction-ID: 61774

process

MAPK cascade

increases_activity of

gene/protein

RPS6K

Comment Ribosomal S6 kinase is a downstream target of the MAP kinase cascade. Activated ribosomal S6 kinase phosphorylates CREB, leading to increased expression of the anti-apoptotic BCL-2.
Formal Description
Interaction-ID: 61776

gene/protein

RPS6K

increases_activity of

gene/protein

CREB1

Drugbank entries Show/Hide entries for CREB1
Comment Ribosomal S6 kinase is a downstream target of the MAP kinase cascade. Activated ribosomal S6 kinase phosphorylates CREB, leading to increased expression of the anti-apoptotic BCL-2.
Formal Description
Interaction-ID: 61782

gene/protein

CREB1

increases_expression of

gene/protein

BCL2

Drugbank entries Show/Hide entries for CREB1 or BCL2
Comment Lithium modulates cAMP-mediated signaling. The physiologic effects of cAMP is mediated by activation of protein kinase A which activates the transcription factor CREB, important for long-term neuroplasticity.
Formal Description
Interaction-ID: 61810

drug/chemical compound

Lithium

affects_activity of

Drugbank entries Show/Hide entries for Lithium
Comment Lithium modulates cAMP-mediated signaling. The physiologic effects of cAMP is mediated by activation of protein kinase A which activates the transcription factor CREB, important for long-term neuroplasticity.
Formal Description
Interaction-ID: 61811

increases_activity of

gene/protein

CREB1

Drugbank entries Show/Hide entries for CREB1
Comment CREB1 induces the transcription of BDNF, implicated in neuronal survival and synaptic plasticity.
Formal Description
Interaction-ID: 61812

gene/protein

CREB1

increases_expression of

gene/protein

BDNF

Drugbank entries Show/Hide entries for CREB1
Comment Phosphatidylinositol-mediated signaling affects the expression of SMIT (SLC5A3), a high affinity myoinositol transport system. Activity and mRNA expression of SMIT is downregulated in cultured astrocytes after treatment with lithium.
Formal Description
Interaction-ID: 61813

increases_activity of

gene/protein

SLC5A3

Comment Phosphatidylinositol-mediated signaling affects the expression of SMIT (SLC5A3), a high affinity myoinositol transport system. Activity and mRNA expression of SMIT is downregulated in cultured astrocytes after treatment with lithium.
Formal Description
Interaction-ID: 61814

drug/chemical compound

Lithium

decreases_activity of

gene/protein

SLC5A3

Drugbank entries Show/Hide entries for Lithium
Comment Phosphatidylinositol-mediated signaling affects the expression of SMIT (SLC5A3), a high affinity myoinositol transport system. Activity and mRNA expression of SMIT is downregulated in cultured astrocytes after treatment with lithium.
Formal Description
Interaction-ID: 61815

drug/chemical compound

Lithium

decreases_expression of

gene/protein

SLC5A3

Drugbank entries Show/Hide entries for Lithium
Comment SMIT (SLC5A3) is a high affinity myoinositol transporter.
Formal Description
Interaction-ID: 61816

gene/protein

SLC5A3

increases_transport of

drug/chemical compound

Inositol

Comment The amount of myo-inositol in the plasma membrane modulates PI-signaling.
Formal Description
Interaction-ID: 61817

drug/chemical compound

Inositol

increases_activity of

Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate.
Formal Description
Interaction-ID: 61981

gene/protein

PLC

increases_quantity of

drug/chemical compound

Inositol 1,4,5-trisphosphate

Drugbank entries Show/Hide entries for PLC
Comment Diacylglycerol induces the activity of protein kinase C.
Formal Description
Interaction-ID: 61983

drug/chemical compound

Diacylglycerol

increases_activity of

gene/protein

Protein kinase C

Comment IMPase and IPPase are enzymes involved in recycling and de novo synthesis of inositol, which is a necessary component of the phosphoinositol signaling pathway. Lithium inhibits both enzymes which results in a decrease of myo-inositol and an accumulation of inositol-1-monophosphate.
Formal Description
Interaction-ID: 62196

drug/chemical compound

Lithium

increases_quantity of

drug/chemical compound

Inositol 1-phosphate

Drugbank entries Show/Hide entries for Lithium
Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3). DAG is an activator of protein kinase C and IP3 causes the release of Ca2+ ions from intracellular stores into the cytoplasm.
Formal Description
Interaction-ID: 62202

increases_quantity of

drug/chemical compound

Diacylglycerol

Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3). DAG is an activator of protein kinase C and IP3 causes the release of Ca2+ ions from intracellular stores into the cytoplasm.
Formal Description
Interaction-ID: 62203

increases_quantity of

drug/chemical compound

Inositol 1,4,5-trisphosphate

Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate, which is further hydrolysed to myo-inositol.
Formal Description
Interaction-ID: 62288

gene/protein

INPP1

decreases_quantity of

drug/chemical compound

Inositol 1,4-bisphosphate

Drugbank entries Show/Hide entries for INPP1
Comment IMPase uses myo-inositol phosphate as substrate, which is metabolized to myo-inositol.
Formal Description
Interaction-ID: 62289

gene/protein

IMPA1

decreases_quantity of

drug/chemical compound

Inositol 3-phosphate

Drugbank entries Show/Hide entries for IMPA1
Comment IMPase uses myo-inositol phosphate as substrate, which is metabolized to myo-inositol.
Formal Description
Interaction-ID: 62290

gene/protein

IMPA2

decreases_quantity of

drug/chemical compound

Inositol 3-phosphate

Drugbank entries Show/Hide entries for IMPA2
Comment IMPase uses myo-inositol phosphate as substrate, which is metabolized to myo-inositol.
Formal Description
Interaction-ID: 62342

drug/chemical compound

Inositol 3-phosphate

increases_quantity of

drug/chemical compound

Inositol

Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3). DAG is an activator of protein kinase C and IP3 causes the release of Ca2+ ions from intracellular stores into the cytoplasm.
Formal Description
Interaction-ID: 62345

drug/chemical compound

Diacylglycerol

increases_activity of

gene/protein

Protein kinase C

Comment Inositol is hydrolyzed to phosphatidylinositol-4, 5-bisphosphate (PIP2). Phospholipase C mediates the hydrolysis PIP2, to form the second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3). DAG is an activator of protein kinase C and IP3 causes the release of Ca2+ ions from intracellular stores into the cytoplasm.
Formal Description
Interaction-ID: 62346

drug/chemical compound

Inositol 1,4,5-trisphosphate

increases_activity of

Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate.
Formal Description
Interaction-ID: 62350

gene/protein

INPP1

increases_quantity of

drug/chemical compound

Inositol 4-phosphate

Drugbank entries Show/Hide entries for INPP1
Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate, which is further hydrolysed to myo-inositol. In addition, INPP1 catalyzes the hydrolysis of myo-inositol 1,3,4-triphosphate to myo-inositol 3,4,bisphosphate.
Formal Description
Interaction-ID: 62386

drug/chemical compound

Inositol 1,4-bisphosphate

increases_quantity of

drug/chemical compound

Inositol 4-phosphate

Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate, which is further hydrolysed to myo-inositol. In addition, INPP1 catalyzes the hydrolysis of myo-inositol 1,3,4-triphosphate to myo-inositol 3,4,bisphosphate.
Formal Description
Interaction-ID: 62397

gene/protein

INPP1

decreases_quantity of

drug/chemical compound

Inositol 1,3,4-trisphosphate

Drugbank entries Show/Hide entries for INPP1
Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate, which is further hydrolysed to myo-inositol. In addition, INPP1 catalyzes the hydrolysis of myo-inositol 1,3,4-triphosphate to myo-inositol 3,4,bisphosphate.
Formal Description
Interaction-ID: 62398

gene/protein

INPP1

decreases_quantity of

drug/chemical compound

Inositol 3,4-bisphosphate

Drugbank entries Show/Hide entries for INPP1
Comment Myo-Inositol 3,4-bisphosphate generated via INPP1 is further hydrolyzed to myo-inositol 3-phosphate.
Formal Description
Interaction-ID: 62400

drug/chemical compound

Inositol 3,4-bisphosphate

increases_quantity of

drug/chemical compound

Inositol 3-phosphate

Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate, which is further hydrolysed to myo-inositol. In addition, INPP1 catalyzes the hydrolysis of myo-inositol 1,3,4-triphosphate to myo-inositol 3,4,bisphosphate.
Formal Description
Interaction-ID: 62405

drug/chemical compound

Inositol 4-phosphate

increases_quantity of

drug/chemical compound

Inositol

Comment INPP1 uses 1D-myo-inositol 1,4-bisphosphate as substrate and catalyses the hydrolysis to inositol 4-phosphate, which is further hydrolysed to myo-inositol. In addition, INPP1 catalyzes the hydrolysis of myo-inositol 1,3,4-triphosphate to myo-inositol 3,4,bisphosphate.
Formal Description
Interaction-ID: 62406

drug/chemical compound

Inositol 1,3,4-trisphosphate

increases_quantity of

drug/chemical compound

Inositol 3,4-bisphosphate

Comment Lithium modulates cAMP-mediated signaling. The physiologic effects of cAMP is mediated by activation of protein kinase A which activates the transcription factor CREB, important for long-term neuroplasticity.
Formal Description
Interaction-ID: 62972

drug/chemical compound

Lithium

affects_activity of

drug/chemical compound

Adenylate cyclase

Drugbank entries Show/Hide entries for Lithium
Comment Fructose 1,6-bisphosphatase (FBPase) is a regulator of gluconeogenesis.
Formal Description
Interaction-ID: 63702

gene/protein

FBP

increases_activity of

Comment Phosphoglucomutase (PGM) catalyzes the formation of glucose 1-phosphate from glucose 6-phosphate during glycogenolysis.
Formal Description
Interaction-ID: 63703

gene/protein

PGM

increases_activity of