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Information on EC 2.3.1.50 - serine C-palmitoyltransferase
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2.3.1.50 serine C-palmitoyltransferaseIUBMB Comments
A pyridoxal-phosphate protein.
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Word Map
- 2.3.1.50
- sphingolipids
- ceramide
- sphingomyelin
- myriocin
- sphingosine
- neuropathy
- sphingomyelinase
-
sphingoid
- fumonisin
- glucosylceramide
- dihydrosphingosine
- 3-ketodihydrosphingosine
- corneum
- sphingosine-1-phosphate
- glycosphingolipids
-
plp-dependent
- dihydroceramide
- l-cycloserine
- paucimobilis
-
ormdl3
-
aldimine
-
ceramide-induced
- analysis
-
transepidermal
- medicine
- molecular biology
- asmase
- phytosphingosine
-
charcot-marie-tooth
- sphingomonas
The enzyme appears in viruses and cellular organisms
Synonyms
serine palmitoyltransferase, sptlc1, sptlc2, serine palmitoyl transferase, ssspta, serine-palmitoyltransferase, serine-palmitoyl transferase, serine palmitoyltransferase a, ssspt, lcb2a, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
LCB1
LCB2
LCB2a
serine palmitoyl transferase
serine palmitoyltransferase
serine-palmitoyl transferase
serine-palmitoyltransferase
SPT
additional information
serine palmitoyltransferase
-
-
serine palmitoyltransferase
-
SPT
-
-
additional information
-
the amount of enzyme activity in microsomes is inversely correlated with the amount of the major coat Gag protein of the L-A dsRNA virus particles
additional information
-
SPT belongs to the fold type I family of the pyridoxal 5'-phosphate-dependent enzymes, and the alpha-oxamine synthase subfamily enzymes
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
ordered bi-bi mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
formation of the external aldimine intermediate
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
using 1HNMR the exchange of the alpha-proton of L-serine with the solvent in the presence and absence of S-(2- oxoheptadecyl)-CoA, the structural analogue of palmitoyl-CoA is investagated. Results demonstrate the presence of substrate synergism, in which the alpha-proton of L-serine is activated by the binding of the second substrate palmitoyl-CoA
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the enzyme forms a pyridoxal 5'-phosphate-L-serine-aldimine intermediate during the reaction, His159 plays multiple roles in the reaction mechanism by exploiting the stereochemistry of Dunathan’s conjecture. His159 promotes both the Claisen-type condensation as an acid catalyst and the protonation at Calpha of the second quinonoid to form the pyridoxal 5'-phosphate-KDS aldimine, spectral analysis, overview
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the enzyme forms an external aldimine intermediate, as well as dunathan and quinoid intermediates, and followed by external beta-keto acid intermediate, and finally product quinoid and product external aldimine intermediates, reaction cycle, overview
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the enzyme forms an external aldimine intermediate, as well as dunathan and quinoid intermediates, followed by external beta-keto acid intermediate, and finally product quinoid and product external aldimine intermediates, reaction cycle, overview
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
via reaction intermediate pyridoxal 5'-phosphate-L-serine aldimine, His138 changes its hydrogen bond partner from the carboxyl group of L-serine to the carbonyl group of palmitoyl-CoA upon the binding of palmitoyl-CoA, making the L-serine Ca–H bond perpendicular to the pyridoxal 5'-phosphate-Schiff base plane, reaction mechanism with substrate synergism in the SPT reaction, overview. Modelling of reaction intermediates
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
pyridoxal 5'-phosphate dependent reaction mechanism, key active site residues are His159, Asp231, His234, and Lys265
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the reaction proceeds via a key carbanion/quinonoid species and an internal aldimine/PLP-bound form of the enzyme
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the reaction proceeds via a key carbanion/quinonoid species and an internal aldimine/PLP-bound form of the enzyme
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the reaction proceeds via several intermediate states, the pyridoxal 5'-phosphate cofactor binds to an active site lysine residue as an internal aldimine/Schiff’s base (I). The L-serine displaces the lysine residue (Lys265) to form the PLP-L-serine external aldimine (II). Deprotonation of II gives a carbanion/quinonoid species (III) which condenses in a Claisen-like manner with the acyl-CoA thioester substrate to form a PLP-beta-keto acid, which then decarboxylates to generate the PLP-KDS product quinonoid (IV). This then reprotonates to form PLP-KDS aldimine (V) which is finally displaced by Lys265. The step releasing CoA and CO2 and producing the quinonoid intermediate species is irreversible. Interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate occurs in the formation of the external aldimine II, overview
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
via reaction intermediate pyridoxal 5'-phosphate-L-serine aldimine, His138 changes its hydrogen bond partner from the carboxyl group of L-serine to the carbonyl group of palmitoyl-CoA upon the binding of palmitoyl-CoA, making the L-serine Ca–H bond perpendicular to the pyridoxal 5'-phosphate-Schiff base plane, reaction mechanism with substrate synergism in the SPT reaction, overview. Modelling of reaction intermediates
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
ordered bi-bi mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the enzyme forms an external aldimine intermediate, as well as dunathan and quinoid intermediates, and followed by external beta-keto acid intermediate, and finally product quinoid and product external aldimine intermediates, reaction cycle, overview
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
condensation
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating)
A pyridoxal-phosphate protein.
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CAS REGISTRY NUMBER
COMMENTARY
62213-50-7
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidoyl-CoA + L-serine
CoA + 2-amino-1-hydroxydocosan-3-one + CO2
-
37% activity compared to that with palmitoyl-CoA
-
?
elaidoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-trans-11-eicosen-3-one + CO2
-
39% activity compared to that with palmitoyl-CoA
-
?
L-serine + stearoyl-CoA
CoA + (2S)-2-amino-1-hydroxyicosan-3-one + CO2
-
-
-
?
myristoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
-
46% activity compared to that with palmitoyl-CoA
-
?
oleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-11-cis-eicosen-3-one + CO2
-
57% activity compared to that with palmitoyl-CoA
-
?
palmitoyl-CoA + L-serine
3-dehydrosphinganine + CoA + CO2
-
-
-
?
stearoyl-CoA + L-serine
(2S)-2-amino-1-hydroxyicosan-3-one + CoA + CO2
-
-
-
?
stearoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyeicosan-3-one + CO2
-
51% activity compared to that with palmitoyl-CoA
-
?
heptadecanoyl-CoA + L-serine
?
-
less than 50% activity compared to palmitoyl-CoA
-
?
heptadecanoyl-CoA + L-serine
?
-
less than 50% activity compared to palmitoyl-CoA
-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
lauroyl-CoA + L-serine
CoA + 2-amino-1-hydroxytetradecan-3-one + CO2
-
18% activity compared to that with palmitoyl-CoA
-
?
lauroyl-CoA + L-serine
CoA + 2-amino-1-hydroxytetradecan-3-one + CO2
18% activity compared to palmitoyl-CoA
-
?
myristoyl-CoA + L-serine
?
-
less than 50% activity compared to palmitoyl-CoA
-
?
myristoyl-CoA + L-serine
?
-
less than 50% activity compared to palmitoyl-CoA
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
-
the viral enzyme exhibits preference for myristoyl-CoA rather than palmitoyl-CoA
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
-
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
second best substrate
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
-
75% activity compared to that with palmitoyl-CoA
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
-
75% activity compared to that with palmitoyl-CoA
-
?
myristoyl-CoA + L-serine
CoA + ? + CO2
-
recombinant SPTLC3 subunit in HEK-293 cells
-
?
n-heptadecanoyl-CoA + L-serine
CoA + 2-amino-1-hydroxynonadecan-3-one + CO2
-
75% activity compared to that with palmitoyl-CoA
-
?
n-heptadecanoyl-CoA + L-serine
CoA + 2-amino-1-hydroxynonadecan-3-one + CO2
-
75% activity compared to that with palmitoyl-CoA
-
?
palmitoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-octadecen-3-one + CO2
-
80% activity compared to that with palmitoyl-CoA
-
?
palmitoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-octadecen-3-one + CO2
-
80% activity compared to that with palmitoyl-CoA
-
?
palmitoyl-CoA + L-alanine
CoA + (2S)-2-aminooctadecan-3-one + CO2
wild-type enzyme can metabolize L-alanine under certain conditions
-
?
palmitoyl-CoA + L-alanine
CoA + (2S)-2-aminooctadecan-3-one + CO2
low activity with the wild-type enzyme, but increased activity with some mutants of the enzyme, overview
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
step in the sphingolipid biosynthetic pathway, overview
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the viral enzyme exhibits preference for myristoyl-CoA rather than palmitoyl-CoA
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme of sphingolipid metabolism
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
optimal palmitoyl-CoA concentration is 0.2 mM
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is used in preference to other saturated or unsaturated acyl-CoA substrates
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
100% activity
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
100% activity
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is used in preference to other saturated or unsaturated acyl-CoA substrates
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
initial step of de novo ceramide biosynthesis
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyzes the initial and rate-limiting step in de novo sphingolipid synthesis. Potential role for overexpression of SPT in processes of cell metastasis
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids, the dynamic composition of the SPT complex could provide a cellular mechanism to adjust SPT activity to tissue specific requirements in sphingolipid synthesis
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first and rate-limiting step in the de novo synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme in ceramide synthesis, overview
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
i.e. 2-amino-1-hydroxyoctadecane-3-one, i.e. 3-oxo-dihydroxysphingosine
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
activities are greatest with palmitoyl-CoA and palmitelaidoyl-CoA, followed by fully saturated homologs, activity considerably diminishes as the alkyl-chain length increases or decreases, or with the presence of a cis-double bond
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
no other amino acids can substitute for serine
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the first step in the ceramide biosynthesis pathway
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme is involved in the ceramide metabolism, overview
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
100% activity
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
no other amino acids can substitute for serine
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
His159 is the anchoring site for L-serine and regulates the alpha-deprotonation of L-serine by fixing the conformation of the pyridoxal 5'-phosphate-L-serine aldimine to prevent unwanted side reactions
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate. This interaction is important for substrate specificity and optimal catalytic efficiency
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
no other amino acids can substitute for serine
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
i.e. 2-amino-1-hydroxyoctadecane-3-one, i.e. 3-oxo-dihydroxysphingosine
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
pentadecanoyl-CoA + L-serine
?
-
less than 50% activity compared to palmitoyl-CoA
-
?
pentadecanoyl-CoA + L-serine
?
-
less than 50% activity compared to palmitoyl-CoA
-
?
stearoyl-CoA + L-serine
CoA + (2S)-2-amino-1-hydroxyicosan-3-one + CO2
-
-
-
?
stearoyl-CoA + L-serine
CoA + (2S)-2-amino-1-hydroxyicosan-3-one + CO2
-
-
?
additional information
?
-
the LCB2 subunit of the sphingolipid biosynthesis enzyme SPT can function as an attenuator of the hypersensitive response and Bax-induced cell death, overview
-
?
additional information
?
-
-
the viral single-chain enzyme might form multiprotein complexes in vivo with functions different from the monomer
-
?
additional information
?
-
-
increasing the acyl-CoA chain length above C16 by 1 or 2 carbons is less detrimental to activity than similar decrements in chain length
-
?
additional information
?
-
-
44% reduction of SPT activity in patiens with hereditary sensory neuropathy type I with mutation T399G in the SPTLC1 gene. However the decrease in SPT activity has no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death. Despite the inhibition of mutant allele, the activity of nonmutant allele of SPT may be sufficient for adequate sphingolipid biosynthesis and cell viability. The neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effects of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal proteins
-
?
additional information
?
-
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
?
additional information
?
-
-
mutations in the enzyme subunit SPTLC1 cause hereditary sensory and autonomic neuropathy type I, HSAN1, an adult onset, autosomal dominant neuropathy, HSAN1 patients have reduced SPT activity, link between mutant SPT and neuronal dysfunction
-
?
additional information
?
-
-
the expression of two SPT isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific requirements of sphingolipid synthesis
-
?
additional information
?
-
-
ability of the ssSPT subunits to modulate the chain lengths of LCBs in mammalian cells
-
?
additional information
?
-
-
assay optimization measuring radio-labeled L-serine incorporation into 3-oxodihydrosphingosine in microsomes or crude cell lysate, usage of an nonradioactive HPLC-based detection protocol, overview
-
?
additional information
?
-
1-deoxysphingolipids are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase due to a promiscuous use of L-alanine over its canonical substrate L-serine. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
-
?
additional information
?
-
-
1-deoxysphingolipids are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase due to a promiscuous use of L-alanine over its canonical substrate L-serine. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
-
?
additional information
?
-
the small subunit of serine palmitoyltransferase a (ssSPTa) as an lysophosphatidylinositol acyltransferase 1 (LPIAT1)-interacting protein
-
?
additional information
?
-
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
?
additional information
?
-
-
stearoyl-CoA desaturase-1 deficiency, SCD1 deficiency, reduces ceramide synthesis by downregulating SPT and increasing beta-oxidation in skeletal muscle
-
?
additional information
?
-
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
?
additional information
?
-
no activity with L-phosphoserine
-
?
additional information
?
-
no activity with octanoyl-CoA
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
myristoyl-CoA + L-serine
CoA + ? + CO2
-
recombinant SPTLC3 subunit in HEK-293 cells
-
-
?
palmitoyl-CoA + L-alanine
CoA + (2S)-2-aminooctadecan-3-one + CO2
wild-type enzyme can metabolize L-alanine under certain conditions
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
step in the sphingolipid biosynthetic pathway, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme of sphingolipid metabolism
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyzes the initial and rate-limiting step in de novo sphingolipid synthesis. Potential role for overexpression of SPT in processes of cell metastasis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids, the dynamic composition of the SPT complex could provide a cellular mechanism to adjust SPT activity to tissue specific requirements in sphingolipid synthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first and rate-limiting step in the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme in ceramide synthesis, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the first step in the ceramide biosynthesis pathway
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme is involved in the ceramide metabolism, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
additional information
?
-
the LCB2 subunit of the sphingolipid biosynthesis enzyme SPT can function as an attenuator of the hypersensitive response and Bax-induced cell death, overview
-
-
?
additional information
?
-
-
the viral single-chain enzyme might form multiprotein complexes in vivo with functions different from the monomer
-
-
?
additional information
?
-
-
44% reduction of SPT activity in patiens with hereditary sensory neuropathy type I with mutation T399G in the SPTLC1 gene. However the decrease in SPT activity has no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death. Despite the inhibition of mutant allele, the activity of nonmutant allele of SPT may be sufficient for adequate sphingolipid biosynthesis and cell viability. The neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effects of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal proteins
-
-
?
additional information
?
-
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
-
?
additional information
?
-
-
mutations in the enzyme subunit SPTLC1 cause hereditary sensory and autonomic neuropathy type I, HSAN1, an adult onset, autosomal dominant neuropathy, HSAN1 patients have reduced SPT activity, link between mutant SPT and neuronal dysfunction
-
-
?
additional information
?
-
-
the expression of two SPT isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific requirements of sphingolipid synthesis
-
-
?
additional information
?
-
1-deoxysphingolipids are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase due to a promiscuous use of L-alanine over its canonical substrate L-serine. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
-
-
?
additional information
?
-
-
1-deoxysphingolipids are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase due to a promiscuous use of L-alanine over its canonical substrate L-serine. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
-
-
?
additional information
?
-
the small subunit of serine palmitoyltransferase a (ssSPTa) as an lysophosphatidylinositol acyltransferase 1 (LPIAT1)-interacting protein
-
-
?
additional information
?
-
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
-
?
additional information
?
-
-
stearoyl-CoA desaturase-1 deficiency, SCD1 deficiency, reduces ceramide synthesis by downregulating SPT and increasing beta-oxidation in skeletal muscle
-
-
?
additional information
?
-
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
bound to epsilon-amino group of a lysine residue in the active site
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate can be resolved from the enzyme by dialysis
pyridoxal 5'-phosphate
-
all subunits contain a pyridoxal 5'-phosphate consensus motif sequence
pyridoxal 5'-phosphate
dependent on, bound at the active site at the dimer interface
pyridoxal 5'-phosphate
-
dependent on, the re face of SPT of the pyridoxal 5'-phosphate-Lys aldimine is occupied by a His159 residue instead of an aromatic amino acid residue as in the other type I enzymes
pyridoxal 5'-phosphate
subunit LCB2 possesses a binding site
pyridoxal 5'-phosphate
the pyridoxal 5'-phosphate binding site is required for the LCB2 gene cell death inducing function
pyridoxal 5'-phosphate
dependent on, bound by lysine 265 residue on subunit LCB2a
pyridoxal 5'-phosphate
dependent on, bound by lysine 265 residue, interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate. This interaction is important for substrate specificity and optimal catalytic efficiency
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
additional information
-
NaCl, LiCl, MgCl2, MnCl2 have no effect on activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S,3R)-2-amino-12-hydroxy-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
-
IC50: 5.4 nM
(2S,3R)-2-amino-12-[(Z)-hydroxyimino]-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
-
IC50: 30 nM
(2S,3R)-2-amino-3,12-dihydroxy-2-hydroxymethyl-octadecanoic acid
-
IC50: 3.2 nM
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid
-
IC50: 3.5 nM
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid methyl ester
-
IC50: 17 nM
2-chloro-N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]benzamide
-
4-amino-3-isoxazolidone
D-cycloserine and L-cycloserine are inhibitors, L-cycloserine is 14-fold more effective than D-cycloserine
ceramide 1-phosphate
-
from bovine brain, inhibits the enzyme and blocks apoptosis in alveolar macrophages, overview
cis-4-methylsphingosine
-
time- and concentration-dependent, causes drastic morphological changes of the cells in vivo
mycotoxin fumonisin B1
-
enzyme sensitivity to the inhibitor is increased by small subunit ssSPTa overexpression
N-[(7S)-4-(5,6-dimethoxypyridine-3-carbonyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamide
-
palmitoyl CoA
enzyme shows remarkable substrate inhibition at palmitoyl-CoA concentrations higher than 0.1 nM
thermozymocidin
-
i.e. ISP-1; strong inhibition, reversible by sphingosine
[N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-[5-(3-[2-[(3,5-dimethyl-1H-pyrrol-2-yl-kappaN)methylidene]-2H-pyrrol-5-yl-kappaN]propanamido)pentyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamidato](difluorido)boron
-
beta-chloro-L-alanine
-
rapid, irreversible and time dependent inhibition at the active site; stereospecific, no inhibition by beta-chloro-D-alanine; suicide substrate
myriocin
a potent inhibitor of SPT, that has no effect on Bax-induced programmed cell death
myriocin
-
i.e. sphingofungin B; strong inhibition, reversible by sphingosine
myriocin
-
in vivo intraperitoneal application to apolipoprotein E knockout mice leads to inhibition of atherosclerosis while feeding a high fat diet to the mice, and is associated with reduced plasma glycosphingolipid concentration and reduction of lesions in aorta regions, overview
myriocin
-
the inhibition of SPT in hyperlipidemic apolipoprotein E knockout mice lowers plasma sphingolipids and atherogenic plasma lipids leading to the regression of pre-existing atherosclerotic lesions and to the formation of a stable plaque phenotype
myriocin
inhibits the enzyme and inhibits defense response against a nonhost pathogen; inhibits the enzyme and inhibits defense response against a nonhost pathogen
myriocin
-
both short and prolonged time of inhibition of the enzyme by myriocin is sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport
myriocin
i.e. (2S,3R,4R,6E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid, or thermozymocidin and ISP-1, is a fungal natural product, kinetics and molecular mechanism of enzyme inhibition, overview. Myriocin is a potent SPT enzyme inhibitor. It initially forms an external aldimine with pyridoxal 5'-phosphate at the active site, the structure of the resulting co-complex explains its nanomolar affinity for the enzyme. The cofactor-inhibitor co-complex, PLP-myriocin aldimine, catalytically degrades via an unexpected retro-aldol-like cleavage mechanism to a C18 aldehyde which in turn acts as a suicide inhibitor of the enzyme by covalent modification of the essential catalytic lysine. This dual mechanism of inhibition rationalizes the extraordinary potency and longevity of myriocin inhibition. Incubations of enzyme SPT with myriocin is consistent with the formation of an initial enzyme-inhibitor complex which is noncovalent in nature and reversible, albeit with a very slow off rate (koff), the PLP-myriocin aldimine as the initial competitive inhibitory species. In contrast, for the enzyme preincubated with myriocin for 16 h, no detectable regain in activity is observed after dialysis either at 3 or 24 h, the second formed covalent adduct acts as an irreversible inhibitor of enzyme SPT
additional information
-
orosomucoid proteins ORM1 and ORM2 inhibit the function of the small subunit ssSP and thus negatively regulate enzyme activity
-
additional information
-
recombinant expression of C133W mutant SPTLC1 in cell cultures dominantly inhibits the endogenous SPT activity
-
additional information
-
time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent; time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent
-
additional information
time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent; time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent
-
additional information
time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent; time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent
-
additional information
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
additional information
-
short-term inhibition of SPT ameliorates palmitate/ceramide-induced insulin resistance, sustained loss/reduction in SPT expression/activity promotes greater partitioning of palmitate towards diacylglycerol synthesis, which impacts negatively upon IRS1-directed insulin signalling
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pioglitazone
-
increases the enzyme activity in vitro and in vivo independent of standard or high-fat diet
retinoic acid
-
up-regulates enzyme activity in embryonic carcinoma cell ine PCC7-Mz1
S-(2-oxoheptadecyl)-CoA
binds to the smSPT-external aldimine complex and enhances the exchange rate of the alpha-proton of L-serine by smSPT
small activating subunit of serine palmitoyltransferase
-
ssSPT, the small subunits of human serine palmitoyltransferase (hssSPTs) are glycoproteins and activate the catalytic hLCB1/hLCB2 heterodimer. Two isoforms exist, ssSPTa and ssSPTb, a single amino acid, residue 25, difference between ssSPTa and ssSPTb is responsible for the acyl-CoA preference of heterotrimers containing each isoform. the role of the small activating subunits of serine palmitoyltransferase, ssSPTs, is to increase SPT activity without compromising substrate specificity. Activity and acyl-CoA selectivity of the ssSPTs reside in the conserved core. Deletion of the N-terminal 10 amino acids of small activating subunit of serine palmitoyltransferase isoforms ssSPTa or ssSPTb has no effect on the ability of the proteins to activate hLCB1/hLCB2a heterodimers sufficiently to complement growth of yeast lacking endogenous serine palmitoyltransferase. The region responsible for the acyl-CoA selectivity of ssSPTa lays between residues Ser11 and Glu27, the acyl-CoA selectivity does not lie in the C-terminal region of ssSPTb, overview
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etoposide
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enhanced activity due to chemotherapy with epotoside as therapeutic agent in Molt-4 leukemic cells
etoposide
activates enzyme activity, but decreases mRNA level, time-dependent
small subunits of serine palmitoyltransferase
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isoforms ssSPTa and ssSPTb, UniProt A8MSB8 and F4IPU5, strongly stimulate SPT activity. Small subunit ssSPTa transcripts are more enriched in all organs and over 400fold more abundant in pollen than small subunit ssSPTb transcripts. Homozygous ssSPTa T-DNA mutants are not recoverable, and 50% nonviable pollen is detected in heterozygous ssspta mutants. The small subunits are essential for male gametophytes, are important for mycotoxin fumonisin B1 sensitivity, and limit sphingolipid synthesis in planta
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small subunits of serine palmitoyltransferase
small subunits of SPT, ssSPTa and ssSPTb, increase human SPT activity by 50-100fold when coexpressed with enzyme subunits hLCB1 and hLCBa
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additional information
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enzyme activity is enhanced under stress and in apoptosis, e.g. in pancreatic cells in a model for diabetes, in case of angiotensin II type receptor occupancy
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additional information
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enzyme activity is enhanced under stress and in apoptosis, e.g. in pancreatic cells in a model for diabetes, in case of angiotensin II type receptor occupancy
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additional information
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increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
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additional information
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the enzyme activity and expression in the heart is not affected by high-fat feeding
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9.6
L-alanine
-
C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.0129
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.75
L-serine
-
wild type protein, pH not specified in the publication, temperature not specified in the publication
0.78
L-serine
-
pH not specified in the publication, temperature not specified in the publication
1.4
L-serine
-
C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
1.6
L-serine
recombinant wild-type enzyme, pH 7.5, 25°C
5.6
L-serine
mutant enzyme R378K, with palmitoyl-CoA as cosubstrate, at pH 7.5 and 25°C
7.2
L-serine
wild type enzyme, with palmitoyl-CoA as cosubstrate, at pH 7.5 and 25°C
0.0234
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.035
palmitoyl-CoA
pH 7.5, 37°C, recombinant wild-type enzyme
0.0356
palmitoyl-CoA
recombinant wild-type enzyme, pH 7.5, 25°C
additional information
L-alanine
-
wild-type enzyme does not utilize alanine efficiently
additional information
additional information
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kinetics analysis, detailed overview
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additional information
additional information
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kinetics of the recombinant SPTLC3 subunit in HEK-293 cells, overview
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additional information
additional information
Michaelis-Menten kinetics of wild-type and mutant enzyme
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additional information
additional information
Michaelis-Menten kinetics of wild-type and mutant enzymes
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additional information
additional information
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Michaelis-Menten kinetics of wild-type and mutant enzymes
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additional information
additional information
Michaelis-Menten kinetics of wild-type and mutant enzymes
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additional information
additional information
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Michaelis-Menten kinetics of wild-type and mutant enzymes
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additional information
additional information
Michaelis-Menten kinetics.The regenerated enzyme displays similar Km and kcat values to the purified enzyme, with only a small increase in the Km for L-serine
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.083
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.0687
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
1.14
palmitoyl-CoA
recombinant wild-type enzyme, pH 7.5, 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6.416
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.0881
L-serine
-
pH not specified in the publication, temperature not specified in the publication
1.2
L-serine
mutant enzyme R378K, with myristoyl-CoA as cosubstrate, at pH 7.5 and 25°C
1.4
L-serine
wild type enzyme, with myristoyl-CoA as cosubstrate, at pH 7.5 and 25°C
2.936
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
32.02
palmitoyl-CoA
recombinant wild-type enzyme, pH 7.5, 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2
L-alanine
-
wild type protein, substrate serine, pH and temperature not specified in the publication
5
L-alanine
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C133W mutant protein, substrate serine, pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000054
(2S,3R)-2-amino-12-hydroxy-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
Cricetulus griseus
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IC50: 5.4 nM
0.00003
(2S,3R)-2-amino-12-[(Z)-hydroxyimino]-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
Cricetulus griseus
-
IC50: 30 nM
0.0000032
(2S,3R)-2-amino-3,12-dihydroxy-2-hydroxymethyl-octadecanoic acid
Cricetulus griseus
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IC50: 3.2 nM
0.0000035
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid
Cricetulus griseus
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IC50: 3.5 nM
0.000017
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid methyl ester
Cricetulus griseus
-
IC50: 17 nM
0.0000008 - 0.0000041
2-chloro-N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]benzamide
0.00000076 - 0.0000016
N-[(7S)-4-(5,6-dimethoxypyridine-3-carbonyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamide
0.000003
sulfamisterin
Cricetulus griseus
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antibiotic derived from Pycnidiella sp., IC50: 3 nM
0.00000024 - 0.0000008
[N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-[5-(3-[2-[(3,5-dimethyl-1H-pyrrol-2-yl-kappaN)methylidene]-2H-pyrrol-5-yl-kappaN]propanamido)pentyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamidato](difluorido)boron
0.0000008
2-chloro-N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]benzamide
Homo sapiens
subunit SPT2, at pH 8.0 and 25°C
0.0000041
2-chloro-N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]benzamide
Homo sapiens
subunit SPT3, at pH 8.0 and 25°C
0.00000076
N-[(7S)-4-(5,6-dimethoxypyridine-3-carbonyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamide
Homo sapiens
subunit SPT2, at pH 8.0 and 25°C
0.0000016
N-[(7S)-4-(5,6-dimethoxypyridine-3-carbonyl)-1-(propan-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamide
Homo sapiens
subunit SPT3, at pH 8.0 and 25°C
0.00000024
[N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-[5-(3-[2-[(3,5-dimethyl-1H-pyrrol-2-yl-kappaN)methylidene]-2H-pyrrol-5-yl-kappaN]propanamido)pentyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamidato](difluorido)boron
Homo sapiens
subunit SPT2, at pH 8.0 and 25°C
0.0000008
[N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-[5-(3-[2-[(3,5-dimethyl-1H-pyrrol-2-yl-kappaN)methylidene]-2H-pyrrol-5-yl-kappaN]propanamido)pentyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamidato](difluorido)boron
Homo sapiens
subunit SPT3, at pH 8.0 and 25°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000044
0.00011
-
substrate alanine, C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.000275
-
substrate serine, C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.00135
-
substrate serine, wild type protein, pH not specified in the publication, temperature not specified in the publication
0.0104
with [2,3,3-D] L-serine as cosubstrate, at pH 8.1 and 37°C
0.0113
with[2-13C] L-serine as cosubstrate, at pH 8.1 and 37°C
0.0122
with [3,3-D] L-serine as cosubstrate, at pH 8.1 and 37°C
0.0129
with [1,2,3-13C,2-15N] L-serine as cosubstrate, at pH 8.1 and 37°C
0.441
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with [1,2,3-13C,2-15N] L-serine as cosubstrate, at pH 8.1 and 37°C
additional information
additional information
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intramuscular fatty acid composition and ceramide content of wild-type and SCD1-deficiency mice, overview
additional information
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increased enzymatic activity of SPT in reactive astrocytes of the hippocampus after kainate injections is shown
additional information
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enzyme activty and ceramide synthesis in macrophages, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
7.5 - 8
8.3
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
infects the globally important marine calcifying microalga Emiliania huxleyi, gene ehv050
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-
brenda
genetically corrected revertant strain LY-B/cLCB1 of deficient mutant LY-B
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-
brenda
two subunits of SPT, Sptlc1 and Sptlc2, i.e. LCB1 and LCB2 or SPT1 and SPT2
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-
brenda
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-
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brenda
subunits SPTLC1 (O15269) and SPTLC2(O15270); subunits SPTLC1 and SPTLC2
UniProt
brenda
subunit LCB1 fragment; two genes encoding the LCB2 and LCB1 subunits of the enzyme
UniProt
brenda
subunit LCB2; two genes encoding the LCB2 and LCB1 subunits of the enzyme
UniProt
brenda
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-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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the cell shows very low enzyme activity due to deficiency of subunit LCB1
brenda
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protein expression of SPT in both psoriatic epidermis and non-lesional epidermis is investigated. Expression of SPT in psoriatic epidermis is significantly less than that of the non-lesional epidermis, which is inversely correlated with PASI score
brenda
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small subunit ssSPTa transcripts are more enriched in all organs and over 400fold more abundant in pollen than small subunit ssSPTb transcripts
brenda
additional information
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increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
brenda
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increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
brenda
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increased expression of SPT in reactive astrocytes of the hippocampus after kainate injections is shown
brenda
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elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
brenda
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elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
brenda
mucosal from colon, lung, prostate, stomach, thyroid, uterus, vascular tissue
brenda
additional information
ubiquitous expression of subunits LCB1 and LCB2 in the plant
brenda
additional information
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ubiquitous expression of subunits LCB1 and LCB2 in the plant
brenda
additional information
AtLCB1 is expressed ubiquitously in all organs of Arabidopsis thaliana examined, but the transcript level is higher in flowers and stems than in leaves and roots
brenda
additional information
AtLCB1 is expressed ubiquitously in all organs of Arabidopsis thaliana examined, but the transcript level is higher in flowers and stems than in leaves and roots
brenda
additional information
AtLCB2 is expressed ubiquitously in all organs of Arabidopsis thaliana examined, but the transcript level is higher in flowers and stems than in leaves and roots
brenda
additional information
AtLCB2 is expressed ubiquitously in all organs of Arabidopsis thaliana examined, but the transcript level is higher in flowers and stems than in leaves and roots
brenda
additional information
BcLCB2 expression is detected by RT-PCR in all nonheading Chinese cabbage organs
brenda
additional information
not in neuronal cells like astrocytes, microglia, and oligodendritic cells, not in skin and heart
brenda
additional information
not in neuronal cells like astrocytes, microglia, and oligodendritic cells, not in skin and heart
brenda
additional information
-
not in neuronal cells like astrocytes, microglia, and oligodendritic cells, not in skin and heart
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
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the Lcb1p and Lcb2p subunits of the SPT heterodimer may interact in the cytosol, as well as within the membrane and/or the lumen of the endoplasmic reticulum
brenda
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the N-terminal is orientated to the lumenal side, the C-terminal is orienated to the cytosolic side
brenda
SPT subunit 1 is present in the endoplasmic reticulum
brenda
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lumen, the Lcb1p and Lcb2p subunits of the SPT heterodimer may interact in the cytosol, as well as within the membrane and/or the lumen of the endoplasmic reticulum
brenda
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the enzyme is a transmembrane protein