Harpers

GLUCONEOGENESIS & CONTROL OF THE BLOOD GLUCOSE / 159Glucose is formed from two groups of compoundsthat undergo gluconeogenesis (Figures 16–4 and 19–1):(1) those which involve a direct net conversion to glucosewithout significant recycling, such as some aminoacids and propionate; and (2) those which are theproducts of the metabolism of glucose in tissues. Thus,lactate, formed by glycolysis in skeletal muscle anderythrocytes, is transported to the liver and kidneywhere it re-forms glucose, which again becomes availablevia the circulation for oxidation in the tissues. Thisprocess is known as the Cori cycle, or lactic acid cycle(Figure 19–4). Triacylglycerol glycerol in adipose tissueis derived from blood glucose. This triacylglycerol iscontinuously undergoing hydrolysis to form free glycerol,which cannot be utilized by adipose tissue and isconverted back to glucose by gluconeogenic mechanismsin the liver and kidney (Figure 19–1).Of the amino acids transported from muscle to theliver during starvation, alanine predominates. The glucose-alaninecycle (Figure 19–4) transports glucosefrom liver to muscle with formation of pyruvate, followedby transamination to alanine, then transportsalanine to the liver, followed by gluconeogenesis backto glucose. A net transfer of amino nitrogen from muscleto liver and of free energy from liver to muscle is effected.The energy required for the hepatic synthesis ofglucose from pyruvate is derived from the oxidation offatty acids.Glucose is also formed from liver glycogen byglycogenolysis (Chapter 18).Metabolic & Hormonal MechanismsRegulate the Concentrationof the Blood GlucoseThe maintenance of stable levels of glucose in the bloodis one of the most finely regulated of all homeostaticmechanisms, involving the liver, extrahepatic tissues,and several hormones. Liver cells are freely permeableto glucose (via the GLUT 2 transporter), whereas cellsof extrahepatic tissues (apart from pancreatic B islets)are relatively impermeable, and their glucose transportersare regulated by insulin. As a result, uptakefrom the bloodstream is the rate-limiting step in theutilization of glucose in extrahepatic tissues. The role ofvarious glucose transporter proteins found in cell membranes,each having 12 transmembrane domains, isshown in Table 19–2.Glucokinase Is Important in RegulatingBlood Glucose After a MealHexokinase has a low K m for glucose and in the liver issaturated and acting at a constant rate under all normalconditions. Glucokinase has a considerably higher K m(lower affinity) for glucose, so that its activity increasesover the physiologic range of glucose concentrations(Figure 19–5). It promotes hepatic uptake of largeamounts of glucose at the high concentrations found inthe hepatic portal vein after a carbohydrate meal. It isabsent from the liver of ruminants, which have littleBLOODGlucoseLIVERMUSCLEGlucose 6-phosphateGlycogenGlycogenGlucose 6-phosphateUreaPyruvateLactateLactatePyruvate–NH 2AlanineTransaminationLactateBLOODPyruvateTransamination–NH 2AlanineAlanineFigure 19–4.The lactic acid (Cori) cycle and glucose-alanine cycle.