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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue--or decrease in force generation--is a reduction of simultaneously attached cross-bridges in the force generating state. Two processes are necessary for the force generation: Firstly Ca++ release from the sarcoplasmic reticulum to the sarcoplasm and the binding of Ca++ by the troponin molecule and secondly the turnover of myosin-actin cross-bridges. These processes require energy in at least three different ATPase reactions and can consequently be inhibited when ATP hydrolysis is decreased, i.e. when ATP content is to low or when the reaction products (ADP, Pi and H+) reach inhibiting levels or when muscle pH has decreased to values inhibiting actomyosin ATPase activity (22). Low pH will also decrease Ca++ release and Ca++ affinity by troponin (23). In isometric contraction the force is well preserved as long as ADP phosphorylation can be provided by both PCr degradation and anaerobic glycolysis. When the PCr store is exhausted the force starts to decline and if muscle activation is maintained the force will continue to decrease along with falling glycolytic rate. ADP phosphorylation rate decreases successively and ATP content falls with an at least transient increase in ADP. The ATP decrease, apart from the minor increase in ADP, is balanced by an equimolar increase in IMP. Lactate accumulation produces an increasing acidity with muscle pH values down to 6.25. Early changes in free ADP content cannot be excluded as reason for the initial decrease in force production followed by more pronounced inhibition of ATPase activity during continued contraction due to both substrate lack and product inhibition together with pH effect on the excitation--contraction mechanism. In dynamic exercise with supramaximum work intensity the relation between fatigue development and metabolism is similar. In prolonged dynamic exercise relying on oxidative metabolism without lactate formation the point of fatigue is reached when the glycogen store is exhausted. Again ADP phosphorylation rate is decreased when the energy substrate is changed from carbohydrate to fat with lower maximum rate of ATP resynthesis.
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PMID:Biochemistry of muscle fatigue. 396 54

The four acidity constants of threefold protonated xanthosine 5'-monophosphate, H3(XMP)+, reveal that at the physiological pH of 7.5 (XMP-H)(3-) strongly dominates (and not XMP(2-) as given in textbooks); this is in contrast to the related inosine (IMP(2-)) and guanosine 5'-monophosphate (GMP(2-)) and it means that XMP should better be named as xanthosinate 5'-monophosphate. In addition, evidence is provided for a tautomeric (XMP-HN1)(3-)/(XMP-HN3)(3-) equilibrium. The stability constants of the M(H;XMP)+ species were estimated and those of the M(XMP) and M(XMP-H)- complexes (M2+=Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+) measured potentiometrically in aqueous solution. The primary M2+ binding site in M(XMP) is (mostly) N7 of the monodeprotonated xanthine residue, the proton being at the phosphate group. The corresponding macrochelates involving P(O)2(OH)- (most likely outer-sphere) are formed to approximately 65% for nearly all M2+. In M(XMP-H)- the primary M2+ binding site is (mostly) the phosphate group; here the formation degree of the N7 macrochelates varies widely from close to zero for the alkaline earth ions, to approximately 50% for Mn2+, and approximately 90% or more for Co2+, Ni2+, Cu2+, Zn2+, and Cd2+. Because for (XMP-H)(3-) the micro stability constants quantifying the M2+ affinity of the xanthosinate and PO3(2-) residues are known, one may apply a recently developed quantification method for the chelate effect to the corresponding macrochelates; this chelate effect is close to zero for the alkaline earth ions and it amounts to about one log unit for Co2+, Ni2+, Cu2+. This method also allows calculation of the formation degrees of the monodentatally coordinated isomers; this information is of relevance for biological systems because it demonstrates how metal ions can switch from one site to another through macrochelate formation. These insights are meaningful for metal-ion-dependent reactions of XMP in metabolic pathways; previous mechanistic proposals based on XMP(2-) need revision.
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PMID:Acid-base and metal-ion-binding properties of xanthosine 5'-monophosphate (XMP) in aqueous solution: complex stabilities, isomeric equilibria, and extent of macrochelation. 1688 37