Saccharopine Dehydrogenase

File:PDB 1e5l EBI.jpg

Saccharopine dehydrogenase from Magnaporthe grisea

Identifiers
Symbol| Saccharop_dh
Pfam| PF03435
Pfam clan| CL0063
InterPro| IPR005097
SCOP| 1ff9
SUPERFAMILY| 1ff9
| Available protein structures:

Pfam| structures
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary
saccharopine dehydrogenase (putative)

Identifiers
Symbol| SCCPDH
Entrez| 51097
HUGO| 24275
RefSeq| NM_016002
UniProt| Q8NBX0
Other data
Locus| Chr. 1 q44

In molecular biology, the protein domain Saccharopine dehydrogenase (SDH), also named Saccharopine reductase, is an enzyme involved in the metabolism of the amino acid lysine, via an intermediate substance called saccharopine. The Saccharopine dehydrogenase enzyme can be classified under EC 1.5.1.7, EC 1.5.1.8, EC 1.5.1.9, and EC 1.5.1.10. It has an important function in lysine metabolism and catalyses a reaction in the alpha-Aminoadipic acid pathway. This pathway is unique to fungal organisms therefore, this molecule could be useful in the search for new antibiotics. This protein family also includes saccharopine dehydrogenase and homospermidine synthase. It is found in prokaryotes, eukaryotes and archaea.

## Contents

* 1 Function
* 2 Structure
* 3 Clinical significance
* 4 References

## Function

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Simplistically, SDH uses NAD+ as an oxidant to catalyse the reversible pyridine nucleotide dependent oxidative deamination of the substrate, Saccharopine, in order to form the products, lysine and alpha-ketoglutarate. This can be described by the following equation:[1]

SDH

Saccharopine ⇌ lysine + alpha-ketoglutarate

Saccharopine dehydrogenase EC catalyses the condensation to of l-alpha-aminoadipate-delta-semialdehyde (AASA) with l-glutamate to give an imine, which is reduced by NADPH to give saccharopine.[2] In some organisms this enzyme is found as a bifunctional polypeptide with lysine ketoglutarate reductase (PF).

Homospermidine synthase proteins (EC). Homospermidine synthase (HSS) catalyses the synthesis of the polyamine homospermidine from 2 mol putrescine in an NAD+-dependent reaction.[3]

## Structure

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There appears to be two protein domains of similar size. One domain is a Rossmann fold that binds NAD+/NADH, and the other is relatively similar. Both domains contain a six-stranded parallel beta-sheet surrounded by alpha-helices and loops (alpha/beta fold).[4]

## Clinical significance

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Deficiencies are associated with hyperlysinemia.

## References

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1. ↑ Kumar VP, West AH, Cook PF (June 2012). "Supporting role of lysine 13 and glutamate 16 in the acid-base mechanism of saccharopine dehydrogenase from Saccharomyces cerevisiae". Archives of Biochemistry and Biophysics. 522 (1): 57–61. doi:10.1016/j.abb.2012.03.027. PMID 22521736.
2. ↑ Vashishtha AK, West AH, Cook PF (June 2009). "Chemical mechanism of saccharopine reductase from Saccharomyces cerevisiae". Biochemistry. 48 (25): 5899–907. doi:10.1021/bi900599s. PMID 19449898.
3. ↑ Tholl D, Ober D, Martin W, Kellermann J, Hartmann T (September 1996). "Purification, molecular cloning and expression in Escherichia coli of homospermidine synthase from Rhodopseudomonas viridis". European Journal of Biochemistry. 240 (2): 373–9. doi:10.1111/j.1432-1033.1996.0373h.x. PMID 8841401.
4. ↑ Andi B, Xu H, Cook PF, West AH (November 2007). "Crystal structures of ligand-bound saccharopine dehydrogenase from Saccharomyces cerevisiae". Biochemistry. 46 (44): 12512–21. doi:10.1021/bi701428m. PMID 17939687.

* Saccharopine+Dehydrogenases at the US National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

Oxidoreductases: CH-NH (EC 1.5)

1.5.1: NAD or NADP acceptor|

* Dihydrofolate reductase
* Saccharopine dehydrogenase
* Methylenetetrahydrofolate reductase

1.5.3: oxygen acceptor|

* Dihydrobenzophenanthridine oxidase
* Sarcosine oxidase
* Proline oxidase

1.5.5: quinone acceptor|

* Electron-transferring-flavoprotein dehydrogenase

1.5.99|

* Sarcosine dehydrogenase
* Cytokinin dehydrogenase

* v
* t
* e

Metabolism: Protein metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA|

| LYSINE→|

* Saccharopine dehydrogenase
* Glutaryl-CoA dehydrogenase

|

LEUCINE→|

* 3-Hydroxybutyryl-CoA dehydrogenase
* Branched-chain amino acid aminotransferase
* Branched-chain alpha-keto acid dehydrogenase complex
* Enoyl-CoA hydratase
* HMG-CoA lyase
* HMG-CoA reductase
* Isovaleryl coenzyme A dehydrogenase
* α-Ketoisocaproate dioxygenase
* Leucine 2,3-aminomutase
* Methylcrotonyl-CoA carboxylase
* Methylglutaconyl-CoA hydratase

(See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase)

TRYPTOPHAN→|

* Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase
* Arylformamidase
* Kynureninase
* 3-hydroxyanthranilate oxidase
* Aminocarboxymuconate-semialdehyde decarboxylase
* Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→|

* (see below)

| G→pyruvate
→citrate|

| glycine→serine→|

* Serine hydroxymethyltransferase
* Serine dehydratase

* glycine→creatine: Guanidinoacetate N-methyltransferase
* Creatine kinase

|

alanine→|

* Alanine transaminase

cysteine→|

* D-cysteine desulfhydrase

threonine→|

* L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate|

| HISTIDINE→|

* Histidine ammonia-lyase
* Urocanate hydratase
* Formiminotransferase cyclodeaminase

|

proline→|

* Proline oxidase
* Pyrroline-5-carboxylate reductase
* 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1
* PYCR1

arginine→|

* Ornithine aminotransferase
* Ornithine decarboxylase
* Agmatinase

→alpha-ketoglutarate→TCA|

* Glutamate dehydrogenase

Other|

* cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase
* Glutathione synthetase
* Gamma-glutamyl transpeptidase

* glutamate→glutamine: Glutamine synthetase
* Glutaminase

G→propionyl-CoA→
succinyl-CoA|

| VALINE→|

* Branched-chain amino acid aminotransferase
* Branched-chain alpha-keto acid dehydrogenase complex
* Enoyl-CoA hydratase
* 3-hydroxyisobutyryl-CoA hydrolase
* 3-hydroxyisobutyrate dehydrogenase
* Methylmalonate semialdehyde dehydrogenase

|

ISOLEUCINE→|

* Branched-chain amino acid aminotransferase
* Branched-chain alpha-keto acid dehydrogenase complex
* 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→|

* generation of homocysteine: Methionine adenosyltransferase
* Adenosylhomocysteinase

* regeneration of methionine: Methionine synthase/Homocysteine methyltransferase
* Betaine-homocysteine methyltransferase

* conversion to cysteine: Cystathionine beta synthase
* Cystathionine gamma-lyase

THREONINE→|

* Threonine aldolase

→succinyl-CoA→TCA|

* Propionyl-CoA carboxylase
* Methylmalonyl CoA epimerase
* Methylmalonyl-CoA mutase

G→fumarate|

| PHENYLALANINE→tyrosine→|

* Phenylalanine hydroxylase
* Tyrosine aminotransferase
* 4-Hydroxyphenylpyruvate dioxygenase
* Homogentisate 1,2-dioxygenase
* Fumarylacetoacetate hydrolase

* tyrosine→melanin: Tyrosinase

|

G→oxaloacetate|

| asparagine→aspartate→|

* Asparaginase/Asparagine synthetase
* Aspartate transaminase

|

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