The purpose of this review and commentary was to provide an historical and evidence-based account of organic acids and the biochemical and organic chemistry evidence for why cells do not produce metabolites that are a...The purpose of this review and commentary was to provide an historical and evidence-based account of organic acids and the biochemical and organic chemistry evidence for why cells do not produce metabolites that are acids.The scientific study of acids has a long history dating to the 16th and 17th centuries,and the definition of an acid was proposed in 1884 as a molecule that when in an aqueous solution releases a hydrogen ion(H^(+)).There are three common ionizable functional groups for molecules classified as acids:1)the carboxyl group,2)the phos-phoryl group and 3)the amine group.The propensity by which a cation will associate or dissociate with a negatively charged atom is quantified by the equilibrium constant(K_(eq))of the dissociation constant(K_(d))of the ionization(K_(eq)=K_(d)),which for lactic acid(HLa)vs.lactate(La^(-))is expressed as:K_(eq)=K_(d)=[H^(+)][La^(-)]/[HLa]=4677.3514(ionic strength=0.01 Mol⋅L^(-1),T=25℃).The negative log10 of the dissociation pKd reveals the pH at which half of the molecules are ionized,which for HLa=3.67.Thus,knowing the pKd and the pH of the solution at question will reveal the extent of the ionization vs.acidification of molecules that are classified as acids.展开更多
The purpose of this manuscript was to present the evidence for why cells do not produce metabolic acids.In addition,evidence that opposes common viewpoints and arguments used to support the cellular production of lact...The purpose of this manuscript was to present the evidence for why cells do not produce metabolic acids.In addition,evidence that opposes common viewpoints and arguments used to support the cellular production of lactic acid(HLa)or liver keto-acids have been provided.Organic chemistry reveals that many molecules involved in cellular energy catabolism contain functional groups classified as acids.The two main acidic functional groups of these molecules susceptible to-H^(+) þrelease are the carboxyl and phosphoryl structures,though the biochemistry and organic chemistry of molecules having these structures reveal they are produced in a non-acidic ionic(negatively charged)structure,thereby preventing pH dependent -H^(+)þrelease.Added evidence from the industrial production of HLa further reveals that lactate(La)is produced followed by an acidification step that converts La to HLa due to pH dependent-H^(+)þassociation.Interestingly,there is a plentiful list of other molecules that are classified as acids and compared to HLa have similar values for their Hþdissociation constant(pKd).For many metabolic conditions,the cumulative turnover of these molecules is far higher than for La.The collective evidence documents the non-empirical basis for the construct of the cellular production of HLa,or any other metabolic acid.展开更多
文摘The purpose of this review and commentary was to provide an historical and evidence-based account of organic acids and the biochemical and organic chemistry evidence for why cells do not produce metabolites that are acids.The scientific study of acids has a long history dating to the 16th and 17th centuries,and the definition of an acid was proposed in 1884 as a molecule that when in an aqueous solution releases a hydrogen ion(H^(+)).There are three common ionizable functional groups for molecules classified as acids:1)the carboxyl group,2)the phos-phoryl group and 3)the amine group.The propensity by which a cation will associate or dissociate with a negatively charged atom is quantified by the equilibrium constant(K_(eq))of the dissociation constant(K_(d))of the ionization(K_(eq)=K_(d)),which for lactic acid(HLa)vs.lactate(La^(-))is expressed as:K_(eq)=K_(d)=[H^(+)][La^(-)]/[HLa]=4677.3514(ionic strength=0.01 Mol⋅L^(-1),T=25℃).The negative log10 of the dissociation pKd reveals the pH at which half of the molecules are ionized,which for HLa=3.67.Thus,knowing the pKd and the pH of the solution at question will reveal the extent of the ionization vs.acidification of molecules that are classified as acids.
文摘The purpose of this manuscript was to present the evidence for why cells do not produce metabolic acids.In addition,evidence that opposes common viewpoints and arguments used to support the cellular production of lactic acid(HLa)or liver keto-acids have been provided.Organic chemistry reveals that many molecules involved in cellular energy catabolism contain functional groups classified as acids.The two main acidic functional groups of these molecules susceptible to-H^(+) þrelease are the carboxyl and phosphoryl structures,though the biochemistry and organic chemistry of molecules having these structures reveal they are produced in a non-acidic ionic(negatively charged)structure,thereby preventing pH dependent -H^(+)þrelease.Added evidence from the industrial production of HLa further reveals that lactate(La)is produced followed by an acidification step that converts La to HLa due to pH dependent-H^(+)þassociation.Interestingly,there is a plentiful list of other molecules that are classified as acids and compared to HLa have similar values for their Hþdissociation constant(pKd).For many metabolic conditions,the cumulative turnover of these molecules is far higher than for La.The collective evidence documents the non-empirical basis for the construct of the cellular production of HLa,or any other metabolic acid.
