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Literature summary extracted from

  • Hallen, A.; Jamie, J.F.; Cooper, A.J.
    Lysine metabolism in mammalian brain an update on the importance of recent discoveries (2013), Amino Acids, 45, 1249-1272 .
    View publication on PubMedView publication on EuropePMC

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.25 3,5,3'-triiodothyronine the ketimine reductase activity of CRYM is strongly inhibited by the thyroid hormone T3 Bos taurus
1.5.1.25 3,5,3'-triiodothyronine the ketimine reductase activity of CRYM is strongly inhibited by the thyroid hormone T3 Homo sapiens
1.5.1.25 3,5,3'-triiodothyronine the ketimine reductase activity of CRYM is strongly inhibited by the thyroid hormone T3 Macropus giganteus
1.5.1.25 3,5,3'-triiodothyronine the ketimine reductase activity of CRYM is strongly inhibited by the thyroid hormone T3 Mus musculus
1.5.1.25 3,5,3'-triiodothyronine the ketimine reductase activity of CRYM is strongly inhibited by the thyroid hormone T3, especially at neutral pH, reversible inhibition Rattus norvegicus
1.5.1.25 3,5,3'-triiodothyronine the ketimine reductase activity of CRYM is strongly inhibited by the thyroid hormone T3 Sus scrofa

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.5.1.1 cytosol
-
Rattus norvegicus 5829
-
1.5.1.1 cytosol
-
Sus scrofa 5829
-
1.5.1.1 soluble
-
Rattus norvegicus
-
-
1.5.1.1 soluble
-
Sus scrofa
-
-
1.5.1.21 cytosol
-
Mus musculus 5829
-
1.5.1.21 cytosol
-
Rattus norvegicus 5829
-
1.5.1.21 cytosol
-
Sus scrofa 5829
-
1.5.1.21 cytosol
-
Bos taurus 5829
-
1.5.1.21 soluble
-
Mus musculus
-
-
1.5.1.21 soluble
-
Rattus norvegicus
-
-
1.5.1.21 soluble
-
Sus scrofa
-
-
1.5.1.21 soluble
-
Bos taurus
-
-
1.5.1.25 cytosol
-
Mus musculus 5829
-
1.5.1.25 cytosol
-
Homo sapiens 5829
-
1.5.1.25 cytosol
-
Rattus norvegicus 5829
-
1.5.1.25 cytosol
-
Sus scrofa 5829
-
1.5.1.25 cytosol
-
Bos taurus 5829
-
1.5.1.25 cytosol
-
Macropus giganteus 5829
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.5.1.21 50000
-
-
Bos taurus
1.5.1.21 70000
-
-
Sus scrofa

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.1.1 1-piperideine-2-carboxylate + NAD(P)H + H+ Rattus norvegicus
-
L-pipecolate + NAD(P)+
-
r
1.5.1.1 1-piperideine-2-carboxylate + NAD(P)H + H+ Sus scrofa
-
L-pipecolate + NAD(P)+
-
r
1.5.1.1 1-pyrroline-2-carboxylate + NAD(P)H + H+ Rattus norvegicus
-
L-proline + NAD(P)+
-
r
1.5.1.1 1-pyrroline-2-carboxylate + NAD(P)H + H+ Sus scrofa
-
L-proline + NAD(P)+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+ Mus musculus
-
L-pipecolate + NADP+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+ Rattus norvegicus
-
L-pipecolate + NADP+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+ Sus scrofa
-
L-pipecolate + NADP+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+ Bos taurus
-
L-pipecolate + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+ Mus musculus
-
L-proline + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+ Rattus norvegicus
-
L-proline + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+ Sus scrofa
-
L-proline + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+ Bos taurus
-
L-proline + NADP+
-
r
1.5.1.25 1-piperideine 2-carboxylate + NADPH + H+ Homo sapiens
-
L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+ Mus musculus
-
L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+ Rattus norvegicus
-
L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+ Sus scrofa
-
L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+ Bos taurus
-
L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+ Macropus giganteus
-
L-pipecolate + NADP+
-
?
1.5.1.25 S-(2-aminoethyl)-L-cysteine ketimine + NADPH + H+ Mus musculus
-
1,4-thiomorpholine-3-carboxylate + NADP+
-
?
1.5.1.25 S-(2-aminoethyl)-L-cysteine ketimine + NADPH + H+ Homo sapiens
-
1,4-thiomorpholine-3-carboxylate + NADP+
-
?
1.5.1.25 S-(2-aminoethyl)-L-cysteine ketimine + NADPH + H+ Rattus norvegicus
-
1,4-thiomorpholine-3-carboxylate + NADP+
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.1 Rattus norvegicus
-
-
-
1.5.1.1 Sus scrofa
-
-
-
1.5.1.21 Bos taurus
-
-
-
1.5.1.21 Mus musculus
-
-
-
1.5.1.21 Rattus norvegicus
-
-
-
1.5.1.21 Sus scrofa
-
-
-
1.5.1.25 Bos taurus
-
-
-
1.5.1.25 Homo sapiens
-
-
-
1.5.1.25 Macropus giganteus
-
-
-
1.5.1.25 Mus musculus
-
-
-
1.5.1.25 Rattus norvegicus
-
-
-
1.5.1.25 Sus scrofa
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.5.1.1 native enzyme from kidney Rattus norvegicus
1.5.1.1 native enzyme partially from kidney Sus scrofa
1.5.1.21 native enzyme from kidney Sus scrofa
1.5.1.21 native enzyme from kidney Bos taurus
1.5.1.25 purified from bovine brain Bos taurus
1.5.1.25 purified from lamb brain Macropus giganteus
1.5.1.25 purified from porcine kidney Sus scrofa
1.5.1.25 purified from rat liver Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.5.1.1 brain high enzyme activity Rattus norvegicus
-
1.5.1.1 brain cortex
-
Rattus norvegicus
-
1.5.1.1 cardiac muscle
-
Rattus norvegicus
-
1.5.1.1 kidney
-
Rattus norvegicus
-
1.5.1.1 kidney high enzyme activity Sus scrofa
-
1.5.1.1 spleen
-
Rattus norvegicus
-
1.5.1.1 testis
-
Rattus norvegicus
-
1.5.1.21 brain
-
Bos taurus
-
1.5.1.21 brain especially in frontal and temporal cortex, the level of L-pipecolate is highest in the cerebellum Rattus norvegicus
-
1.5.1.21 brain especially in frontal and temporal cortex, with the striatum having the maximal specific activity. Both the level of L-pipecolate and P2C/Pyr2C reductase-specific activity differed considerably among the different brain regions Mus musculus
-
1.5.1.21 cerebellum
-
Bos taurus
-
1.5.1.21 kidney high enzyme activity Sus scrofa
-
1.5.1.25 brain
-
Homo sapiens
-
1.5.1.25 brain
-
Sus scrofa
-
1.5.1.25 brain
-
Bos taurus
-
1.5.1.25 brain levels of thyroid hormone binding capacity for cytosolic NADPH-dependent T3 binding are noticeably lower in the cerebellum than in the cerebrum of adult rat brain at all stages of development. NADPH-dependent T3 binding is only detected in kidney, liver, heart and spleen after birth, increasing over the next 6 weeks. NADPH-dependent T3 binding is detected in cerebrum and cerebellum 5 days before birth, increasing with a sharp transient spike at the time of birth, that is specific for the brain, particularly in cerebrum, and cannot be seen in other tissues. The NADPH-dependent T3 binding in cerebrum decreases after birth, but begins to increase again 2 weeks after birth. The level in cerebellum does not show this increase. The brain may contain at least two distinct P2C reductases/ketimine reductase, one of which is predominant in the fore-brain and another that is prominent in the cerebellum Rattus norvegicus
-
1.5.1.25 brain very low expression in cerebellum compared to cerebrum, high overall expression level Mus musculus
-
1.5.1.25 cerebellum
-
Mus musculus
-
1.5.1.25 cerebellum
-
Rattus norvegicus
-
1.5.1.25 cerebrum
-
Mus musculus
-
1.5.1.25 cerebrum
-
Rattus norvegicus
-
1.5.1.25 heart high enzyme expression level Mus musculus
-
1.5.1.25 inner ear
-
Homo sapiens
-
1.5.1.25 kidney
-
Sus scrofa
-
1.5.1.25 lens
-
Macropus giganteus
-
1.5.1.25 liver
-
Rattus norvegicus
-
1.5.1.25 additional information CRYM/KR mRNA in the mouse is most highly expressed in skin among the tissues evaluated, followed by brain and heart Mus musculus
-
1.5.1.25 skin high enzyme expression level, expression of the CRYM transcript follows the hair growth cycle with a significant increase in expression during mid- and late anagen growth phases Mus musculus
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
1.5.1.25 additional information
-
highly purified recombinantly expressed human CRYM possesses substantial ketimine reductase activity Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.1 1-piperideine-2-carboxylate + NAD(P)H + H+
-
Rattus norvegicus L-pipecolate + NAD(P)+
-
r
1.5.1.1 1-piperideine-2-carboxylate + NAD(P)H + H+
-
Sus scrofa L-pipecolate + NAD(P)+
-
r
1.5.1.1 1-pyrroline-2-carboxylate + NAD(P)H + H+
-
Rattus norvegicus L-proline + NAD(P)+
-
r
1.5.1.1 1-pyrroline-2-carboxylate + NAD(P)H + H+
-
Sus scrofa L-proline + NAD(P)+
-
r
1.5.1.1 additional information the enzyme from kidney shows no activity with DELTA1-pyrroline-5-carboxylate and DELTA1-piperideine-6-carboxylate Rattus norvegicus ?
-
?
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+
-
Mus musculus L-pipecolate + NADP+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+
-
Rattus norvegicus L-pipecolate + NADP+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+
-
Sus scrofa L-pipecolate + NADP+
-
r
1.5.1.21 1-piperideine-2-carboxylate + NADPH + H+
-
Bos taurus L-pipecolate + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+
-
Mus musculus L-proline + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+
-
Rattus norvegicus L-proline + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+
-
Sus scrofa L-proline + NADP+
-
r
1.5.1.21 1-pyrroline-2-carboxylate + NADPH + H+
-
Bos taurus L-proline + NADP+
-
r
1.5.1.25 1-piperideine 2-carboxylate + NADPH + H+
-
Homo sapiens L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+
-
Mus musculus L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+
-
Rattus norvegicus L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+
-
Sus scrofa L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+
-
Bos taurus L-pipecolate + NADP+
-
?
1.5.1.25 DELTA1-piperideine 2-carboxylate + NADPH + H+
-
Macropus giganteus L-pipecolate + NADP+
-
?
1.5.1.25 S-(2-aminoethyl)-L-cysteine ketimine + NADPH + H+
-
Mus musculus 1,4-thiomorpholine-3-carboxylate + NADP+
-
?
1.5.1.25 S-(2-aminoethyl)-L-cysteine ketimine + NADPH + H+
-
Homo sapiens 1,4-thiomorpholine-3-carboxylate + NADP+
-
?
1.5.1.25 S-(2-aminoethyl)-L-cysteine ketimine + NADPH + H+
-
Rattus norvegicus 1,4-thiomorpholine-3-carboxylate + NADP+
-
?

Subunits

EC Number Subunits Comment Organism
1.5.1.21 homodimer
-
Bos taurus

Synonyms

EC Number Synonyms Comment Organism
1.5.1.1 ketimine reductase
-
Rattus norvegicus
1.5.1.1 ketimine reductase
-
Sus scrofa
1.5.1.1 P2C reductase
-
Rattus norvegicus
1.5.1.1 P2C reductase
-
Sus scrofa
1.5.1.1 P2C/Pyr2C reductase
-
Rattus norvegicus
1.5.1.1 P2C/Pyr2C reductase
-
Sus scrofa
1.5.1.21 ketimine reductase
-
Mus musculus
1.5.1.21 ketimine reductase
-
Rattus norvegicus
1.5.1.21 ketimine reductase
-
Sus scrofa
1.5.1.21 ketimine reductase
-
Bos taurus
1.5.1.21 P2C reductase
-
Mus musculus
1.5.1.21 P2C reductase
-
Rattus norvegicus
1.5.1.21 P2C reductase
-
Sus scrofa
1.5.1.21 P2C reductase
-
Bos taurus
1.5.1.21 P2C/Pyr2C reductase
-
Mus musculus
1.5.1.21 P2C/Pyr2C reductase
-
Rattus norvegicus
1.5.1.21 P2C/Pyr2C reductase
-
Sus scrofa
1.5.1.21 P2C/Pyr2C reductase
-
Bos taurus
1.5.1.25 CRYM
-
Mus musculus
1.5.1.25 CRYM
-
Homo sapiens
1.5.1.25 CRYM
-
Rattus norvegicus
1.5.1.25 CRYM
-
Sus scrofa
1.5.1.25 CRYM
-
Bos taurus
1.5.1.25 CRYM
-
Macropus giganteus
1.5.1.25 ketimine reductase
-
Mus musculus
1.5.1.25 ketimine reductase
-
Homo sapiens
1.5.1.25 ketimine reductase
-
Rattus norvegicus
1.5.1.25 ketimine reductase
-
Sus scrofa
1.5.1.25 ketimine reductase
-
Bos taurus
1.5.1.25 ketimine reductase
-
Macropus giganteus
1.5.1.25 mu-crystallin
-
Mus musculus
1.5.1.25 mu-crystallin
-
Homo sapiens
1.5.1.25 mu-crystallin
-
Rattus norvegicus
1.5.1.25 mu-crystallin
-
Sus scrofa
1.5.1.25 mu-crystallin
-
Bos taurus
1.5.1.25 mu-crystallin
-
Macropus giganteus
1.5.1.25 P2C reductase
-
Mus musculus
1.5.1.25 P2C reductase
-
Homo sapiens
1.5.1.25 P2C reductase
-
Rattus norvegicus
1.5.1.25 P2C reductase
-
Sus scrofa
1.5.1.25 P2C reductase
-
Bos taurus
1.5.1.25 P2C reductase
-
Macropus giganteus
1.5.1.25 Thyroid hormone-binding protein
-
Mus musculus
1.5.1.25 Thyroid hormone-binding protein
-
Homo sapiens
1.5.1.25 Thyroid hormone-binding protein
-
Rattus norvegicus
1.5.1.25 Thyroid hormone-binding protein
-
Sus scrofa
1.5.1.25 Thyroid hormone-binding protein
-
Bos taurus
1.5.1.25 Thyroid hormone-binding protein
-
Macropus giganteus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.21 5
-
reduction of 1-piperideine-2-carboxylate Bos taurus
1.5.1.21 5.2
-
reduction of 1-piperideine-2-carboxylate Mus musculus
1.5.1.21 5.2
-
reduction of 1-piperideine-2-carboxylate Rattus norvegicus
1.5.1.21 5.4
-
reduction of 1-pyrroline-2-carboxylate Mus musculus
1.5.1.21 5.4
-
reduction of 1-pyrroline-2-carboxylate Rattus norvegicus
1.5.1.25 5
-
about, with substrate 1-piperideine 2-carboxylate Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.1 additional information NADH and NADPH are equally effective as cofactor for the enzyme purified from rat kidney Rattus norvegicus
1.5.1.1 additional information the enzyme purified from porcine kidney shows equal activity with NADPH and NADH Sus scrofa
1.5.1.1 NADH
-
Rattus norvegicus
1.5.1.1 NADH
-
Sus scrofa
1.5.1.1 NADPH
-
Rattus norvegicus
1.5.1.1 NADPH
-
Sus scrofa
1.5.1.21 additional information the enzyme purified from bovine cerebellum exhibits a marked preference for NADPH over NADH with substrate 1-piperideine-2-carboxylate Bos taurus
1.5.1.21 additional information the enzyme purified from porcine kidney exhibits a marked preference for NADPH over NADH Sus scrofa
1.5.1.21 NADPH
-
Mus musculus
1.5.1.21 NADPH
-
Rattus norvegicus
1.5.1.21 NADPH
-
Sus scrofa
1.5.1.21 NADPH
-
Bos taurus
1.5.1.25 NADPH
-
Mus musculus
1.5.1.25 NADPH
-
Homo sapiens
1.5.1.25 NADPH
-
Rattus norvegicus
1.5.1.25 NADPH
-
Sus scrofa
1.5.1.25 NADPH
-
Bos taurus
1.5.1.25 NADPH
-
Macropus giganteus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.5.1.25 0.000278
-
3,5,3'-triiodothyronine with substrate S-(2-aminoethyl)-L-cysteine ketimine, pH 5.0, temperature not specified in the publication Rattus norvegicus

Expression

EC Number Organism Comment Expression
1.5.1.25 Bos taurus steroid hormones have a marked effect on the expression of CRYM, e.g. androgens induce CRYM expression in bovine mammary glands up
1.5.1.25 Homo sapiens steroid hormones have a marked effect on the expression of CRYM, e.g. androgens induce CRYM expression in human prostate cancer up

General Information

EC Number General Information Comment Organism
1.5.1.25 malfunction significance of CRYM/KR in psychiatric and neurological disease, overview Mus musculus
1.5.1.25 malfunction Significance of CRYM/KR in psychiatric and neurological disease, overview. Two known point mutations of human CRYM, both of which are associated with nonsyndromic deafness Homo sapiens
1.5.1.25 metabolism the enzyme is involved in the pipecolate pathway, i.e. P2C reductase activity Mus musculus
1.5.1.25 metabolism the enzyme is involved in the pipecolate pathway, i.e. P2C reductase activity Homo sapiens
1.5.1.25 metabolism the enzyme is involved in the pipecolate pathway, i.e. P2C reductase activity Rattus norvegicus
1.5.1.25 metabolism the enzyme is involved in the pipecolate pathway, i.e. P2C reductase activity Sus scrofa
1.5.1.25 metabolism the enzyme is involved in the pipecolate pathway, i.e. P2C reductase activity Bos taurus
1.5.1.25 metabolism the enzyme is involved in the pipecolate pathway, i.e. P2C reductase activity Macropus giganteus
1.5.1.25 physiological function mammalian thyroid hormone-binding protein CRYM has an additional biological role as a ketimine reductase, CRYM is a P2C reductase. CRYM shows an extremely strong affinity for 3,5,3'-triiodothyronine T3 in the presence of NADPH. The enzyme seems to be tightly regulated in vivo by 3,5,3'-triiodothyronine (T3) at low concentrations, T3 bioavailability is likely strongly dependent on the pipecolate pathway activity Rattus norvegicus
1.5.1.25 physiological function mammalian thyroid hormone-binding protein CRYM has an additional biological role as a ketimine reductase, CRYM is a P2C reductase. CRYM shows an extremely strong affinity for 3,5,3'-triiodothyronine T3 in the presence of NADPH. The enzyme seems to be tightly regulated in vivo by 3,5,3'-triiodothyronine (T3) at low concentrations, T3 bioavailability is likely strongly dependent on the pipecolate pathway activity Sus scrofa
1.5.1.25 physiological function mammalian thyroid hormone-binding protein CRYM has an additional biological role as a ketimine reductase, CRYM is a P2C reductase. CRYM shows an extremely strong affinity for 3,5,3'-triiodothyronine T3 in the presence of NADPH. The enzyme seems to be tightly regulated in vivo by 3,5,3'-triiodothyronine (T3) at low concentrations, T3 bioavailability is likely strongly dependent on the pipecolate pathway activity Bos taurus
1.5.1.25 physiological function mammalian thyroid hormone-binding protein CRYM has an additional biological role as a ketimine reductase, CRYM is a P2C reductase. CRYM shows an extremely strong affinity for 3,5,3'-triiodothyronine T3 in the presence of NADPH. The enzyme seems to be tightly regulated in vivo by 3,5,3'-triiodothyronine (T3) at low concentrations, T3 bioavailability is likely strongly dependent on the pipecolate pathway activity. Levels of CRYM/KR substrates are important determinants in hearing as CRYM mRNA is highly expressed in human inner ear Homo sapiens
1.5.1.25 physiological function mammalian thyroid hormone-binding protein CRYM has an additional biological role as a ketimine reductase, CRYM is a P2C reductase. CRYM shows an extremely strong affinity for 3,5,3'-triiodothyronine T3 in the presence of NADPH. The enzyme seems to be tightly regulated in vivo by 3,5,3'-triiodothyronine (T3) at low concentrations, T3 bioavailability is likely strongly dependent on the pipecolate pathway activity. Possible involvement of CRYM in the development of mouse hair follicles during the anagen phase. Enzyme substrates (e.g. sulfur-containing cyclic ketimines such as S-(2-aminoethyl)-L-cysteine ketimine) may play a role in regulating cell growth and/or cell differentiation Mus musculus
1.5.1.25 physiological function the thyroid hormone-binding protein CRYM has an additional biological role as a ketimine reductase, CRYM is a P2C reductase. CRYM shows an extremely strong affinity for 3,5,3'-triiodothyronine T3 in the presence of NADPH. The enzyme seems to be tightly regulated in vivo by 3,5,3'-triiodothyronine (T3) at low concentrations, T3 bioavailability is likely strongly dependent on the pipecolate pathway activity Macropus giganteus