Regulation of the branched chain alpha-ketoacid pathway in liver.

Corkey, Barbara E.; Martín-Requero, Ángeles; Wałajtys-Rode, Elżbieta; Williams, R. J.; Williamson, John

doi:10.1016/s0021-9258(18)34125-5

Cited by 71 publications

(7 citation statements)

References 33 publications

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“…derived from [2-14C]MOV that enter the mitochondrial acetyl-CoA, pool, one can calculate precisely the yield of "4C-label from mitochondrial [1-14C]acetyl-CoA to CO2. Our data on the fraction of [1-14C]acetyl-CoA derived from [2-14C]MOV that is converted into 14CO2 in livers from fed and starved rats are similar to those reported by Lund (1978) and by Corkey et al (1982).…”

Section: Discussionsupporting

confidence: 90%

“…strate concentration decreased only 4-fold. This is in contrast with findings of other groups, who reported that the rate of 14CO2 production from [1-14C]MOV by perfused livers (Patel et al, 1981) or incubated hepatocytes (Corkey et al, 1982) was proportional to the concentration of MOV in the range 0.05-0.2 mm. Note that in these other studies the perfusion or incubation medium did not contain glucose.…”

Section: Additions To Perfusion Mediumcontrasting

confidence: 99%

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Assessment of the flux of mitochondrial acetyl-CoA in liver and kidney by using the differential production of 14CO2 from tracers of (1-14C)- and (2-14C)-labelled 4-methyl-2-oxovalerate

Tomera

Kopito

Brunengraber

1983

Biochemical Journal

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Section: Discussionsupporting

confidence: 90%

Section: Additions To Perfusion Mediumcontrasting

confidence: 99%

Assessment of the flux of mitochondrial acetyl-CoA in liver and kidney by using the differential production of 14CO2 from tracers of (1-14C)- and (2-14C)-labelled 4-methyl-2-oxovalerate

Tomera

Kopito

Brunengraber

1983

Biochemical Journal

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“…3-Thiaoctanoyl-CoA was synthesized according to the method of Lau et al (1988). The CoA ligands were purified by HPLC (Corkey et al, 1982), desalted by a Bio-Gel P-2 (Bio-Rad) column, and characterized by NMR.…”

Section: Methodsmentioning

confidence: 99%

Effect of transition-state analogs on the redox properties of medium-chain acyl-CoA dehydrogenase

Johnson¹,

Mancini-Samuelson²,

Stankovich³

1995

Biochemistry

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The binding of substrate/product or transition-state intermediates modifies the properties of medium-chain fatty acyl-CoA dehydrogenase (MCAD) by causing the redox potential to shift positive and the oxygen reactivity to slow by 3000-fold. Two ligands, identified as being the most effective in slowing oxygen reactivity, were 2-azaoctanoyl-CoA and 3-thiaoctanoyl-CoA [Wang, R., & Thorpe, C. (1991) Biochemistry 30, 7895-7901]. We have measured the potential shifts caused by the binding of both ligands to determine which is most similar to the potential shift caused by substrate/product mixture, the assumption being that the best transition-state structural intermediate would give the potential shift most similar to that of substrate/product [Lenn, N.D., Stankovich, M.T., & Liu, H. (1990) Biochemistry 29, 10594-10602]. Both ligands shifted the potential positive, but the shift caused by 2-azaoctanoyl-CoA was 65% that of substrate/product, while 3-thiaoctanoyl-CoA was only 20% of that value. This positive shift is proposed to be caused by a resonance form stabilized by the interaction of the catalytically essential carbonyl of the acyl-CoA with two hydrogen bonds from the enzyme, which induces a partial negative charge on the carbonyl and a partial positive charge on carbon 2 of the ligand and carbon 3 of the substrate/product couple. The X-ray structure shows that carbons 2 and 3 of the substrate/product overlap the diazadiene portion of the flavin ring [Kim, J.-J. P., Wang, M., & Paschke, R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7523-7527].(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Butyl-and octyl-CoA were synthesized according to the method of Blaschkowski et al (1979). The thioether-CoAs were purified by HPLC or by anion-exchange chromatography (Corkey et al, 1982;Lau et al, 1977), desalted by a Bio-Gel P-2 (Bio-Rad) column, and characterized by NMR. Hexadecyl-CoA was the generous gift of Dr. Colin Thorpe.…”

Section: Methodsmentioning

confidence: 99%

Influence of two substrate analogs on thermodynamic properties of medium-chain acyl-CoA dehydrogenase

Johnson

Stankovich²

1993

Biochemistry

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The objective of this work was to identify the key structural functionalities of substrate or product that modulate the thermodynamic properties of medium-chain acyl-CoA dehydrogenase (MCAD). In order to achieve this, two classes of substrate analogues, acetyl-CoA and thioether-CoAs, were complexed with MCAD and their effects on the redox properties of MCAD were measured. A pH dependence study of the redox potential of uncomplexed MCAD allowed us to compare redox properties between complexed and uncomplexed MCAD and to calculate the dissociation constants of the analogues to the three redox states of MCAD. The results from this work indicate that these analogues are not influencing the thermodynamic behavior of MCAD in the same way as natural substrate. Thus, we propose that the following two key structural features of the binding ligand are necessary for mimicking the thermodynamic effects natural substrate has on MCAD: a thioester carbonyl on carbon 1 and a fatty acyl-CoA chain length around 8 carbon units. Furthermore, with the advent of structural knowledge, insights into the interactions of these structural features with MCAD and their influence on MCAD's highly regulated dehydrogenation mechanism are discussed.

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Regulation of the branched chain alpha-ketoacid pathway in liver.

Cited by 71 publications

References 33 publications

Assessment of the flux of mitochondrial acetyl-CoA in liver and kidney by using the differential production of 14CO2 from tracers of (1-14C)- and (2-14C)-labelled 4-methyl-2-oxovalerate

Assessment of the flux of mitochondrial acetyl-CoA in liver and kidney by using the differential production of 14CO2 from tracers of (1-14C)- and (2-14C)-labelled 4-methyl-2-oxovalerate

Effect of transition-state analogs on the redox properties of medium-chain acyl-CoA dehydrogenase

Influence of two substrate analogs on thermodynamic properties of medium-chain acyl-CoA dehydrogenase

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