Abstract
Rat liver branched chain α-ketoacid dehydrogenase has been solubilized and used to investigate the substrate specificity, cofactor requirements, and stabilizing properties of thiamine pyrophosphate for this enzyme. Only the branched chain α-ketoacids are oxidatively decarboxylated with apparent Km values of 30, 32, and 35 μm for α-ketoisovalerate, α-ketoisocaproate and α-keto-β-methylvalerate, respectively. Maximal CO2 release requires the presence of CoASH, NAD+, Mg2+ and thiamine pyrophosphate. The ketoacids competitively inhibit one another, activity for all three show identical pH optimum and heat lability which supports the concept of single enzyme complex acting on all three substrates. The activity can be stabilized by thiamine pyrophosphate which provides a rationale for treatment of maple syrup urine disease with pharmacologic doses of thiamine.
| Original language | English |
|---|---|
| Pages (from-to) | 27-38 |
| Number of pages | 12 |
| Journal | Biochemical Medicine |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 1978 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Substrate specificity and stabilization by thiamine pyrophosphate of rat liver branched chain α-ketoacid dehydrogenase. / Danner, Dean J.; Lemmon, Sandra; Elsas, Louis J.
In: Biochemical Medicine, Vol. 19, No. 1, 01.01.1978, p. 27-38.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Substrate specificity and stabilization by thiamine pyrophosphate of rat liver branched chain α-ketoacid dehydrogenase
AU - Danner, Dean J.
AU - Lemmon, Sandra
AU - Elsas, Louis J.
PY - 1978/1/1
Y1 - 1978/1/1
N2 - Rat liver branched chain α-ketoacid dehydrogenase has been solubilized and used to investigate the substrate specificity, cofactor requirements, and stabilizing properties of thiamine pyrophosphate for this enzyme. Only the branched chain α-ketoacids are oxidatively decarboxylated with apparent Km values of 30, 32, and 35 μm for α-ketoisovalerate, α-ketoisocaproate and α-keto-β-methylvalerate, respectively. Maximal CO2 release requires the presence of CoASH, NAD+, Mg2+ and thiamine pyrophosphate. The ketoacids competitively inhibit one another, activity for all three show identical pH optimum and heat lability which supports the concept of single enzyme complex acting on all three substrates. The activity can be stabilized by thiamine pyrophosphate which provides a rationale for treatment of maple syrup urine disease with pharmacologic doses of thiamine.
AB - Rat liver branched chain α-ketoacid dehydrogenase has been solubilized and used to investigate the substrate specificity, cofactor requirements, and stabilizing properties of thiamine pyrophosphate for this enzyme. Only the branched chain α-ketoacids are oxidatively decarboxylated with apparent Km values of 30, 32, and 35 μm for α-ketoisovalerate, α-ketoisocaproate and α-keto-β-methylvalerate, respectively. Maximal CO2 release requires the presence of CoASH, NAD+, Mg2+ and thiamine pyrophosphate. The ketoacids competitively inhibit one another, activity for all three show identical pH optimum and heat lability which supports the concept of single enzyme complex acting on all three substrates. The activity can be stabilized by thiamine pyrophosphate which provides a rationale for treatment of maple syrup urine disease with pharmacologic doses of thiamine.
UR - http://www.scopus.com/inward/record.url?scp=0017878129&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0017878129&partnerID=8YFLogxK
U2 - 10.1016/0006-2944(78)90004-2
DO - 10.1016/0006-2944(78)90004-2
M3 - Article
C2 - 203270
AN - SCOPUS:0017878129
VL - 19
SP - 27
EP - 38
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 1
ER -