Physiologists have long known that haemoglobin, the molecule that adds the redness to red blood cells and carries oxygen to the tissues, releases its oxygen as the blood vessels constrict. Now, increasing evidence shows that haemoglobin (composed of four complex proteins that surround a central iron atom) is not just a passive oxygen carrier. It actually works with other substances, including nitric oxide (NO), to regulate the flow of blood by adjusting the dilation of blood vessels, and NO in response can adjust how efficiently haemoglobin can carry oxygen. This process, still not fully understood, is presented in a Concepts piece by David J. Singel and Jonathan S. Stamler in the July 15 issue of Nature,1 who speak of the “emergent complexity of haemoglobin.” Nitric oxide produces dilation of blood vessels. Apparently it will hitch onto the alpha or beta subunits of haemoglobin depending on the concentrations of oxygen or carbon dioxide present in the blood, acting as a regulator of NO’s activity in dilating the vessels according to need. For the chemists in the audience,The disposition and reactivity of NO bound to haemoglobin is thus a function of multiple variables, including the other allosteric effectors of haemoglobin (pH; partial pressure of carbon dioxide, pCO2; partial pressure of O2, pO2) and the ratio of their concentrations to haem. Changes in conditions can give rise to stark, rather than subtle, linear changes in the distribution of NO reaction products. This complexity emerges both from the cooperative, nonlinear behaviour of the haemoglobin tetramer and from the branched network of coupled kinetic equations underlying this rich chemistry.So when you are walking casually in the woods, oxygen outnumbers NO, which binds to the beta subunits, generating production of NO-downstream products, and your blood vessels relax. When you see the bear and take off running, the binding of NO changes and “contributes to the matching of blood flow to demand under physiological conditions.” What happens when the bear has you pinned to the ground and is licking your face?In contrast, when micromolar concentrations of NO arise, as in septic shock, the potential problem of excess S-nitroso-haemoglobin and consequent excessive vasodilation is avoided by sequestering NO on the alpha-haems, which additionally lowers the overall oxygen affinity of the protein. This chemistry restricts NO bioavailability while enhancing oxygen delivery.NO works with haemoglobin, therefore, in response to physiological conditions to adjust its ability to carry oxygen, without going berserk under stress. The authors encourage an “appreciation of the complexity” of this process, because “Emerging evidence [shows] that vasodilation by red blood cells is altered in disease, including heart failure, pulmonary hypertension and diabetes….” Knowledge of this self-regulating activity “should open a new field of investigation and could potentially change the practice of medicine.” A related paper in PNAS2 explores additional biologic activities of NO and its reaction products in blood plasma, and suggests that “high-affinity, metal-based reactions in plasma with the haptoglobin-hemoglobin complex modulate plasmatic NO reaction products and limit S-nitrosation at low NO flux.” These products coordinate with hormones, endocrine vasomotor function, and NO transport in the blood vessels.1David J. Stingel and Jonathan S. Stamler, “Blood traffic control,” Nature 430, 297 (15 July 2004); doi:10.1038/430297a.2Wang et al., “Biological activity of nitric oxide in the plasmatic compartment,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0402201101, online preprint July 16, 2004.This wonderful story speaks for itself. We need to be reminded of how many things have to work exactly right for us to do something as simple as taking a walk in the woods. Things are not getting any easier for those who believe a long series of mistakes produced the human body, to say nothing of bears and forests.(Visited 8 times, 1 visits today)FacebookTwitterPinterestSave分享0
Share Facebook Twitter Google + LinkedIn Pinterest The 2016 Ohio State Fair Commercial Cattle Show participants exhibited 25 pens of three for a total of 75 head of commercial steers and heifers on July 31, 2016 during the fair. This year’s event featured a newly added Junior Division. Judging the event were Dick and Bob Jurgens, from Illinois. The show was managed by United Producers, Inc. and the Ohio Cattlemen’s Association served as a sponsor.Prosser Brothers of Urbana, Ohio, exhibited the Overall Grand Champion Lot of 3 in both the Junior and Open Divisions, both of which were also named the Champion Lot of 3 Steers. The Prosser’s Junior Division champions had an average weight of 1,335 pounds and their Champion Open Division entry averaged 1,361 pounds. Austin Wiseman from Malta, Ohio took home the Reserve Champion Lot of 3 honors in the Junior Division with his Pen of 3 Steers, recording an average weight of 1,347 pounds. Winning the Reserve Champion Overall in the Open Division with their Reserve Lot of 3 Steers, weighing an average of 1,272 pounds was Phelps/O’Connor Farms Limousin of Belle Center, Ohio.In the Open Division, Fred Voge, West Alexandria, Ohio hung the banner for the Champion Lot of 3 with his pen of heifers weighing in with an average of 1,280 pounds. The Reserve Champion Lot of 3 Heifers also went to Fred Voge, weighing in at an average weight of 1,179 pounds.Winners of the live show received premiums of more than $5,000 from the Ohio State Fair.JBS Moyer harvested the cattle and supplied the carcass data for the 2016 Ohio State Fair Commercial Cattle Carcass Contest. Hot carcass weights ranging from 597 pounds to 929 pounds. Yield grades ranged from 1 to 4. Over seventy percent of the contest entries fell into the Choice category, and 18 percent graded Prime. This year’s show had zero dark cutting carcasses.In the Junior Division, Grand Champion Carcass honors went to Austin Wiseman from Malta, Ohio with Pen 9. Reserve Champion went to Cameron Young, Huntsville, Ohio with Pen 13.In the Open Division, Grand Champion and Reserve Champion Carcass honors went to Fred Voge with Pen 24 winning the carcass contest and Pen 23 coming in with Reserve Champion honors. Two carcasses from both the Grand and Reserve Champion graded Prime.