Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins

Ramakrishnan, Rajasekhar

doi:10.1016/j.metabol.2007.06.023

“…To the Editor: I appreciate Dr. Kalhan's kind words about my paper [1]. The derivation he provides in his letter is quite correct under the Tracee Steady State assumption, consistent with my equation (7) as he says.…”

Section: Responsementioning

confidence: 57%

Re: “Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins” by Ramakrishnan (Metabolism 2007;56:1550-60)

Kalhan

¹

2008

View full text Add to dashboard Cite

Re: "Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins" by Ramakrishnan (Metabolism 2007;56:1550-60) To the Editor:Dr Ramakrishnan has evaluated in detail the commonly used algorithms for the estimation of whole-body rate of protein synthesis and amino acid oxidation using isotopic tracers in the steady state. The analyses are helpful for the quantification of protein synthesis and oxidation in vivo. I was surprised by his reference to our work (reference 29) and his comment suggesting that we multiply the formula in their Eq. (7) with isotopic enrichment of the tracer infused, implying an error [1].The algorithm used in all our work (references [2-5] and others) is the same as in Eq. (7) as described in detail here: rate of oxidation of tracer carbon (X) = V CO 2 × E CO 2 , where V CO 2 = rate of production of CO 2 and E CO 2 = 13 C enrichment of expired CO 2 . This can be corrected for the potential retention of the label C in the bicarbonate pool, as done by Ramakrishnan. The retention factor (0.81) is not the same under all physiologic states [4].Fraction of the infused tracer oxidized = (V CO 2 × E CO 2 )/ (I × E i ), where I is the rate of infusion of tracer and E i is its 13 C enrichment.Therefore, the rate of oxidation of the substrate = [(V CO 2 × E CO 2 )/(I × E i )] × R a , where R a = rate of appearance of the substrate in the body (blood) compartment.Because R a = I × [(E i /E p ) − 1], therefore the rate of oxidation of tracee or X TSS = [V CO 2 × E CO 2 /I ×This is the same as Eq. (7) of Ramakrishnan. In our work, we have always presented these algorithms in a stepwise manner so that they are easy to understand, rather than lump them in a single complex equation.

show abstract

“…Very often, these variables can not be readily factored; hence, they are all included under the general notation of the rate of synthesis. Although the rate of synthesis is sometimes assumed to follow 0th‐order kinetics, especially at a protein steady state, extrapolation of such simplification to more general conditions requires caution (Ramakrishnan, 2007).…”

Section: Methodological Description Of Protein Turnovermentioning

confidence: 99%

Advances in protein turnover analysis at the global level and biological insights

Li¹

2009

Mass Spectrometry Reviews

View full text Add to dashboard Cite

The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population.

show abstract

Response

Ramakrishnan

¹

2008

Metabolism

Self Cite

0

View full text Add to dashboard Cite

Re: "Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins" by Ramakrishnan (Metabolism 2007;56:1550-60) To the Editor:Dr Ramakrishnan has evaluated in detail the commonly used algorithms for the estimation of whole-body rate of protein synthesis and amino acid oxidation using isotopic tracers in the steady state. The analyses are helpful for the quantification of protein synthesis and oxidation in vivo. I was surprised by his reference to our work (reference 29) and his comment suggesting that we multiply the formula in their Eq. (7) with isotopic enrichment of the tracer infused, implying an error [1].The algorithm used in all our work (references [2-5] and others) is the same as in Eq. (7) as described in detail here: rate of oxidation of tracer carbon (X) = V CO 2 × E CO 2 , where V CO 2 = rate of production of CO 2 and E CO 2 = 13 C enrichment of expired CO 2 . This can be corrected for the potential retention of the label C in the bicarbonate pool, as done by Ramakrishnan. The retention factor (0.81) is not the same under all physiologic states [4].Fraction of the infused tracer oxidized = (V CO 2 × E CO 2 )/ (I × E i ), where I is the rate of infusion of tracer and E i is its 13 C enrichment.Therefore, the rate of oxidation of the substrate = [(V CO 2 × E CO 2 )/(I × E i )] × R a , where R a = rate of appearance of the substrate in the body (blood) compartment.Because R a = I × [(E i /E p ) − 1], therefore the rate of oxidation of tracee or X TSS = [V CO 2 × E CO 2 /I ×This is the same as Eq. (7) of Ramakrishnan. In our work, we have always presented these algorithms in a stepwise manner so that they are easy to understand, rather than lump them in a single complex equation.

show abstract

Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins

Cited by 4 publications

References 40 publications

Re: “Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins” by Ramakrishnan (Metabolism 2007;56:1550-60)

Re: “Alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins” by Ramakrishnan (Metabolism 2007;56:1550-60)

Advances in protein turnover analysis at the global level and biological insights

Response

Contact Info

Product

Resources

About