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Biomedical subjects

W C Ford

Publications and source records attributed to W C Ford.

61 records · Page 4Linked to original sources

Effect of alpha-chlorohydrin on glucose metabolism by spermatozoa from the cauda epididymidis of the rhesus monkey (Macaca mulatta).

Spermatozoa from the cauda epididymidis of the rhesus monkey had metabolic properties similar to those published for ejaculated spermatozoa. The concentration of glycolytic intermediates was low until 2 mM-glucose was added; glucose 6-phosphate, fructose 1,6-bis-phosphate and the triose plhosphates then increased but glycerate 3-phosphate did not. It was concluded that the activity of glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) limited flux through the glycolytic pathway. The production of lactate and CO2 from glucose was strongly inhibited in the presence of 5 or 10 mM-alpha-chlorohydrin. The energy charge of the spermatozoa was low before and after 1 incubation with 2 mM-glucose (0.5 +/- 0.05 and 0.05 +/- 0.06 respectively) and the value after the incubation was decreased in the presence of 5 or 10 mM-alpha-chlorohydrin (0.17 +/- 0.05 and 0.15 +/- 0.04 respectively). alpha-Chlorohydrin inhibited glycolysis at the glyceraldehyde 3-phosphate dehydrogenase reaction.

Adenine Nucleotides↗

A reversible contraceptive action of some 6-chloro-6-deoxy sugars in the male rat.

Male rats given daily doses of 240 mumol 6,6'-dichloro-6,6'-dideoxysucrose or 6'-chloro-6'-deoxysucrose or 6-chloro-6-deoxysucrose/kg for 28 days became infertile after 7 days and remained infertile during treatment. Fertility was partly recovered 3 weeks after the last dose and completely restored by 6 weeks. 6-Chloro-6-deoxyglucose and 6-chloro-6-deoxyfructose were also effective at this dose, but 6,1',6'-trichloro-6,1',6'-trideoxysucrose, 4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose,4,6,-4',6'-tetrachloro-4,6,4',6'-tetradeoxygalactotrehalose and methyl-6-chloro-6-deoxy-alpha-D-glucopyranoside were not. Spermatozoa from the cauda epididymidis of infertile rats oxidized glucose more slowly than did spermatozoa from controls.

Animals↗

Effects of the optical isomers of alpha-chlorohydrin on glycolysis by ram testicular spermatozoa and the fertility of male rats.

When 0-1 mM-S alpha-chlorohydrin was present in incubations, glycolysis by ram testicular spermatozoa was almost completely inhibited whereas 10 mM-R alpha-chlorohydrin had no effect. Male rats dosed orally with S alpha-chlorohydrin (3-25 mg/kg/day) became much less fertile than controls but those dosed with R alpha-chlorohydrin (13 mg/kg/day) did not. The loss of fertility was associated with a reduced ability of spermatozoa from the cauda epididymidis of these rats to oxidize glucose. It is concluded that the S enantiomer is responsible for both the inhibition of sperm glycolysis and the reduction in fertility caused by the racemic mixture of alpha-chlorohydrin.

Animals↗

Regulation of myocardial energy metabolism.

Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition.

Acetyl Coenzyme A↗

The regulation of glycolysis in perfused locust flight muscle.

Concentrations of glycolytic intermediates, amino acids and possible regulator substances were measured in extracts from locust thoracic muscles perfused under different conditions. The conversion of [(14)C]glucose into intermediates and CO(2) by muscle preparations was also followed. When muscles perfused with glucose were made anaerobic changes in metabolite concentrations occurred that could be accounted for by an activation of phosphofructokinase and pyruvate kinase. When butyrate and glucose were present in the perfusion medium the rate of glycolytic flux was lower than with glucose alone, and the aldolase reaction appeared to be inhibited. When butyrate alone was supplied to the muscle the concentrations of most glycolytic intermediates were similar to those found when glucose was supplied. Iodoacetate caused changes in concentrations of intermediates that appeared to result from inhibition of glyceraldehyde 3-phosphate dehydrogenase. Fluoroacetate-poisoned muscles showed a high citrate concentration, but no obvious site of inhibition by citrate was apparent in the glycolytic pathway. Mechanisms for control of glycolysis in locust flight muscle are discussed and related to the known properties of isolated enzymes. It is proposed that trehalase, hexokinase, phosphofructokinase, aldolase, and pyruvate kinase may be control enzymes in this tissue.

Amino Acids↗

The role of glucose in supporting motility and capacitation in human spermatozoa.

Glucose has been reported to be beneficial to human sperm for optimal capacitation and fertilization, although it is unclear whether glucose is required for providing extra metabolic energy through glycolysis, or for generating some other metabolic product. In this study, the effects of sugars on human sperm capacitation, motility, and energy production were investigated. The glucose concentration that supported the greatest number of acrosome reactions was 5.56 mmol L(-1). Compared with incubations with no added sugar, this concentration of glucose, fructose, mannose, or galactose appeared to slightly increase the number of acrosome reactions occurring after 18 hours of capacitation, or following induction by 2 micromol A23187 + 3.6 mmol pentoxifylline L 1, but only glucose had a statistically significant effect. Glucose supported increased penetration of zona-free hamster oocytes, but its advantage was not statistically significant. The addition of 5.56 mmol glucose or fructose L(-1) to sugar-free medium immediately increased the adenosine triphosphate (ATP) concentration and motility of sperm. These parameters were then stable for 3 hours, but declined markedly after 18 hours. In the absence of a glycolysable sugar, motility began to decline in the first hour and only 2% or 3% of sperm remained motile after 18 hours. Glucose or fructose was required to support hyperactivated motility. 2-Deoxyglucose was detrimental to the ATP concentration and motility of sperm, and supported fewer spontaneous or progesterone-stimulated acrosome reactions than were observed in the absence of a sugar. We conclude that glycolytic ATP production is required for vigorous motility and hyperactivation in human sperm. Other products of glucose metabolism are not essential to support capacitation, but they may have a small, enhancing effect.

Acrosome Reaction↗