RGD Reference Report - Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools. - Rat Genome Database

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Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools.

Authors: McKenna, MC  Waagepetersen, HS  Schousboe, A  Sonnewald, U 
Citation: McKenna MC, etal., Biochem Pharmacol. 2006 Feb 14;71(4):399-407. Epub 2005 Dec 20.
RGD ID: 11251688
Pubmed: PMID:16368075   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bcp.2005.10.011   (Journal Full-text)

The malate-aspartate shuttle and the glycerol phosphate shuttle act to transfer reducing equivalents from NADH in the cytosol to the mitochondria since the inner mitochondrial membrane is impermeable to NADH and NAD+. This transfer of reducing equivalents is essential for maintaining a favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of neurotransmitters in brain. There is evidence that both the malate-aspartate shuttle and glycerol phosphate shuttle function in brain; however, there is controversy about the relative importance and cellular localization of these shuttles. The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons and may be extremely low, or even non-existent in brain astrocytes. Several studies provide evidence of glycerol phosphate shuttle activity in brain cells; however, the activity of this shuttle in brain has been questioned. A number of pharmacological tools, including aminooxyacetic acid, beta-methyleneaspartate, phenylsuccinate, and 3-nitropropionic acid, have been used to inhibit the four enzymes and two carrier proteins that participate in the malate-aspartate shuttle. Although no drugs completely inhibit the glycerol phosphate shuttle, evidence for the existence of this shuttle is provided by studies using drugs to inhibit the malate-aspartate shuttle. This report evaluates the evidence for each shuttle in brain cells and the drugs that can be used as pharmacological tools to study these shuttles.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GOT1Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
GOT2Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
GPD1Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
GPD2Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
Got1Ratnicotinamide adenine dinucleotide metabolic pathway   ISOGOT1 (Homo sapiens) RGD 
Got1Mousenicotinamide adenine dinucleotide metabolic pathway   ISOGOT1 (Homo sapiens) RGD 
Got2Ratnicotinamide adenine dinucleotide metabolic pathway   ISOGOT2 (Homo sapiens) RGD 
Got2Mousenicotinamide adenine dinucleotide metabolic pathway   ISOGOT2 (Homo sapiens) RGD 
Gpd1Ratnicotinamide adenine dinucleotide metabolic pathway   ISOGPD1 (Homo sapiens) RGD 
Gpd1Mousenicotinamide adenine dinucleotide metabolic pathway   ISOGPD1 (Homo sapiens) RGD 
Gpd2Ratnicotinamide adenine dinucleotide metabolic pathway   ISOGPD2 (Homo sapiens) RGD 
Gpd2Mousenicotinamide adenine dinucleotide metabolic pathway   ISOGPD2 (Homo sapiens) RGD 
MDH1Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
MDH2Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
Mdh1Ratnicotinamide adenine dinucleotide metabolic pathway   ISOMDH1 (Homo sapiens) RGD 
Mdh1Mousenicotinamide adenine dinucleotide metabolic pathway   ISOMDH1 (Homo sapiens) RGD 
Mdh2Mousenicotinamide adenine dinucleotide metabolic pathway   ISOMDH2 (Homo sapiens) RGD 
Mdh2Ratnicotinamide adenine dinucleotide metabolic pathway   ISOMDH2 (Homo sapiens) RGD 
SLC1A3Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
SLC25A12Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
SLC25A13Humannicotinamide adenine dinucleotide metabolic pathway   TAS  RGD 
Slc1a3Ratnicotinamide adenine dinucleotide metabolic pathway   ISOSLC1A3 (Homo sapiens) RGD 
Slc1a3Mousenicotinamide adenine dinucleotide metabolic pathway   ISOSLC1A3 (Homo sapiens) RGD 
Slc25a12Ratnicotinamide adenine dinucleotide metabolic pathway   ISOSLC25A12 (Homo sapiens) RGD 
Slc25a12Mousenicotinamide adenine dinucleotide metabolic pathway   ISOSLC25A12 (Homo sapiens) RGD 
Slc25a13Mousenicotinamide adenine dinucleotide metabolic pathway   ISOSLC25A13 (Homo sapiens) RGD 
Slc25a13Ratnicotinamide adenine dinucleotide metabolic pathway   ISOSLC25A13 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Got1  (glutamic-oxaloacetic transaminase 1)
Got2  (glutamic-oxaloacetic transaminase 2)
Gpd1  (glycerol-3-phosphate dehydrogenase 1)
Gpd2  (glycerol-3-phosphate dehydrogenase 2)
Mdh1  (malate dehydrogenase 1)
Mdh2  (malate dehydrogenase 2)
Slc1a3  (solute carrier family 1 member 3)
Slc25a12  (solute carrier family 25 member 12)
Slc25a13  (solute carrier family 25 member 13)

Genes (Mus musculus)
Got1  (glutamic-oxaloacetic transaminase 1, soluble)
Got2  (glutamatic-oxaloacetic transaminase 2, mitochondrial)
Gpd1  (glycerol-3-phosphate dehydrogenase 1 (soluble))
Gpd2  (glycerol phosphate dehydrogenase 2, mitochondrial)
Mdh1  (malate dehydrogenase 1, NAD (soluble))
Mdh2  (malate dehydrogenase 2, NAD (mitochondrial))
Slc1a3  (solute carrier family 1 (glial high affinity glutamate transporter), member 3)
Slc25a12  (solute carrier family 25 (mitochondrial carrier, Aralar), member 12)
Slc25a13  (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 13)

Genes (Homo sapiens)
GOT1  (glutamic-oxaloacetic transaminase 1)
GOT2  (glutamic-oxaloacetic transaminase 2)
GPD1  (glycerol-3-phosphate dehydrogenase 1)
GPD2  (glycerol-3-phosphate dehydrogenase 2)
MDH1  (malate dehydrogenase 1)
MDH2  (malate dehydrogenase 2)
SLC1A3  (solute carrier family 1 member 3)
SLC25A12  (solute carrier family 25 member 12)
SLC25A13  (solute carrier family 25 member 13)


Additional Information