Difference between revisions of "Lactate dehydrogenase"

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| <ref name="Brooks_1999"> Brooks GA (1999). ''Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?''. Adv Exp Med Biol, 474:185–204 </ref>
 
| <ref name="Brooks_1999"> Brooks GA (1999). ''Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?''. Adv Exp Med Biol, 474:185–204 </ref>
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| Lehninger, (1975)<ref name="lehninger75">Lehninger, A.L. (1975) Biochemistry (2nd edn), Worth</ref> p 407:<br/>
 
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==References==
 
==References==
 
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Revision as of 11:19, 1 July 2014


A dehydrogenase is an enzyme that transfers a hydride from one molecule to another. Lactate dehydrogenase catalyzes the conversion of pyruvate to lactate and back, as it converts NADH to NAD+ and back.

Chemical reactions

NADH + PYR \rightleftharpoons Lactate_{in} + NAD^+

Rate equation

RAndom Bi-Bi reversible Michaelis-Menten equation is used. [1]

\frac{V_{mf}\frac{[NADH][PYR]}{Km_{NADH} K_{PYR}} - V_{mr}\frac{[Lactate_{in}][NAD]}{Km_{Lactate_{in}} K_{NAD}}}{1 + \frac{[NADH]}{Km_{NADH}} + \frac{[PYR]}{Km_{PYR}} + \frac{[NADH][PYR]}{Km_{NADH} Km_{PYR}} + \frac{[Lactate_{in}][NAD]}{Km_{Lactate_{in}} Km_{NAD}} + \frac{[Lactate_{in}]}{Km_{Lactate_{in}}} + \frac{[PYR]}{Km_{PYR}} }

Modified rate law to take Thermodynamic constraint into consideration

\frac{V_{mf}\frac{[NADH][PYR]}{Km_{NADH} K_{PYR}} \left(1 - \frac{[Lactate_{in}][NAD]}{K_{eq}[NADH][PYR]} \right)}{1 + \frac{[NADH]}{Km_{NADH}} + \frac{[PYR]}{Km_{PYR}} + \frac{[NADH][PYR]}{Km_{NADH} Km_{PYR}} + \frac{[Lactate_{in}][NAD]}{Km_{Lactate_{in}} Km_{NAD}} + \frac{[Lactate_{in}]}{Km_{Lactate_{in}}} + \frac{[PYR]}{Km_{PYR}} }

Prameter values

Parameter Value Units Organism Remarks
V_{mf} 3.4 [1] \text{mM min}^{-1} HeLa cell line
V_{mr} 0.54 \text{mM min}^{-1} HeLa cell line
Km_{PYR} 0.1 mM HeLa cell line
Km_{LAC} 4.7 mM Rat AS-30D hepatoma
Km_{NAD} 0.07 mM HeLa cell line
Km_{NADH} 0.002 mM HeLa cell line

Parameters with uncertainty

  • Mean and Std. Dev. for V_{mf} has been reported in Table S3 for Marín-Hernández (2011) et. al. [1]. The Std. Dev. for V_{mr} is calculated based on the same ratio for V_{mf}.
  • Reported values of Km_{PYR} are 0.03 [2], 0.398 [3], 0.3 [1]. The mean value with std. dev. is 0.24 \pm 0.19.
  • The value for Km_{NAD} and Km_{NADH} has been reported for Ovine (Sheep) as Km_{NAD} = 3.96 \pm 0.17 and Km_{NADH} = 0.097 \pm 0.020 [4]. Due to lack of data in Human cells these two values are considered in our model.
  • Km_{LAC} = 4 for LDH-1 and 2 isoforms and Km_{LAC} = 7 for LDH-4 and 5 isoforms are being reported in Marín-Hernández et. al. (2009)[5]. Mean and Std. Dev. from these two values are 5.5 \pm 2.12
Parameter Value Units Organism Remarks
V_{mf} Failed to parse (Cannot store math image on filesystem.): 3.4 \pm 0.5 (3) [6] \text{mM min}^{-1} HeLa cell line
V_{mr} 0.54 \pm 0.073 \text{mM min}^{-1} HeLa cell line
Km_{PYR} 0.24 \pm 0.19 mM HeLa cell line
Km_{LAC} 5.5 \pm 2.12 mM Rat AS-30D hepatoma
Km_{NAD} 3.96 \pm 0.17 mM 
Ovine (Sheep)
Km_{NADH} 0.097 \pm 0.020 mM 
Ovine (Sheep)


Equilibrium constant

Equilibrium constant Conditions Source
36000 [7]
0.067 pH=7, T=25°C Lehninger, (1975)[8] p 407:

References

  1. ↑ 1.0 1.1 1.2 1.3 Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 (doi)
  2. ↑ LeVan K.M., Goldberg E. (1991), Properties of human testis-specific lactate dehydrogenase expressed from Escherichia coli, Biochem. J. 273, 587-592 (1991)
  3. ↑ Pettit S.M., Nealon D.A., Henderson A.R. (1981), Purification of lactate dehydrogenase isoenzyme-5 from human liver, Clin. Chem. 27, 88-93 (1981)
  4. ↑ M. Doughty (1998), Some kinetic properties of lactate dehydrogenase activity in cell extracts from a mammalian (ovine) corneal epithelium, Exp. Eye Res., 66, pp. 231–239
  5. ↑ A. Marín-Hernández, J.C. Gallardo-Pérez, S.J. Ralph, S. Rodríguez-Enríquez, R. Moreno-Sánchez (2009), HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms, Mini Rev. Med. Chem., 9, pp. 1084–1101
  6. ↑ Marín-Hernández A , Rodríguez-Enríquez S, Vital-González P A, et al. (2006). Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an over-expressed but strongly product-inhibited hexokinase. FEBS J., 273 , pp. 1975–1988(doi)
  7. ↑ Brooks GA (1999). Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?. Adv Exp Med Biol, 474:185–204
  8. ↑ Lehninger, A.L. (1975) Biochemistry (2nd edn), Worth
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