Robert H. Herman

Control of jejunal sucrase and maltase activity by dietary sucrose or fructose in man. A model for the study of enzyme regulation in man.

The specific effect of dietary sugars on jejunal disaccharidase activity in seven normal nonfasted male volunteers was studied. The sugars tested were sucrose, maltose, lactose, glucose, fructose, and galactose. Comparisons were made of the effects of each sugar in an isocaloric liquid diet. In all subjects, sucrose feeding, as compared to glucose feeding, significantly increased jejunal sucrase (S) and maltase (M) activities, but not lactase (L) activity. The S/L and M/L ratios increased to a significant degree. Fructose feeding, in two subjects, gave results similar to sucrose when comparing fructose and glucose diets. One subject was fed lactose, galactose, and maltose. These sugars, compared to glucose, did not increase disaccharidase activity. Fructose appears to be the active principle in the sucrose molecule. These results demonstrate that specific dietary sugars can alter enzyme activity in the small intestine of man in a specific fashion. Sucrose and fructose are able to regulate sucrase and maltase activity. Dietary alteration of intestinal enzymes may represent a suitable system for studying the regulation of enzyme activity in man.

Mechanism for the differential effects of high carbohydrate diets on lipogenesis in rat liver.

Abstract 1. 1. The changes in the hepatic concentration of glycolytic and tricarboxylic acid cycle intermediates, the conversion of [14C6]glucose and [14C6]fructose to fatty acids and CO2 in liver slices, and the activity of certain lipogenic and glycolytic enzymes in the liver have been compared in fasted rats refed a chow diet or diets high in glucose or fructose content. These measurements have been correlated with the effects of the different diets on the hepatic and serum triglyceride concentration. 2. 2. The animals fed the fructose diet had the highest hepatic and serum triglyceride concentrations whereas the chow-fed animals had the lowest. 3. 3. Several differences were noted between fructose, glucose or chow-fed rats in the concentration of glycolytic and tricarboxylic acid cycle intermediates. Most important, fructose feeding was associated with a greater hepatic concentration of pyruvate, CoASAc and malate than in either the glucose or chow-fed groups. The conversion of [14C6]fructose to fatty acids was increased by either the fructose or glucose diet in comparison to the chow diet. Further, in each dietary group more [14C6]fructose than [14C6]glucose was incorporated into fatty acids, indicating that the synthesis of hepatic fatty acids from glucose was not limited by the activity of the fatty acid synthesizing enzymes. 4. 4. The activity of fructokinase (ATP : d -fructose 1-phosphotransferase, EC 2.7.1.3) was greater than that of glucokinase (ATP : d -glucose 6-phosphotransf erase, EC 2.7.1.2) and hexokinase (ATP : d -glucose 6-phosphotransferase, EC 2.7.1.1) in all diet groups. As a result more fructose than glucose could be phosphorylated in rat liver. In comparison to the chow-fed rats the hepatic CoASAc-carboxylase (CoASAc : carbon-dioxide ligase (ADP), EC 6.4.1.2) activity was increased to the same extent by the fructose or glucose feeding. 5. 5. It is concluded that the mechanism for the differential effects of high carbohydrate diets on hepatic fatty acid synthesis depends upon the higher rate of CoASAc formation from fructose as compared to glucose. The difference m the activity for the glucose and fructose phosphorylating enzymes in rat liver could account for the different rates at which fructose and glucose were metabolized to CoASAc. A secondary effect is that either a high glucose or fructose diet increases the hepatic activity of CoASAc carboxylase.

Dietary regulation of glycolytic enzymes I. Adaptive changes in rat jejunum

Abstract 1. 1. The effects of dietary fructose, sucrose, glucose, casein and fasting upon the activity of several glycolytic enzymes [fructokinase (ketohexokinase, EC 2.7.1.3), hexokinase (ATP: D -hexose 6-phosphotransferase, EC 2.7.1.1), glucokinase (ATP: D -hexose 6-phosphotransferase, EC 2.7.1.2), Fru- I -P aldolase (ketose- I -phosphate aldehyde-lyase, EC 4.1.2.7), Fru- I ,6-P 2 aldolase (fructose- I ,6-diphosphate D -glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) and aldose reductase (alditol:NADP+ oxidoreductase, EC 1.1.1.21)] were studied in the jejunum of rats. 2. 2. Individual sugars (glucose, sucrose and fructose) have specific carbohydrate effects on certain jejunal glycolytic enzymes. Fructose had a specific adaptive effect upon fructokinase and Fru- I -P aldolase, while glucose exerted its adaptive effect upon hexokinase and glucokinase. The addition of calories in the form of casein to fasted rats caused a non-specific increase in the activity of all jejunal glycolytic enzymes studied. 3. 3. Changes in rat jejunal glycolytic enzymes due to diet reflect those in rat liver. 4. 4. The ratio of Fru- I ,6-P 2 / Fru- I -P adolase activities in the liver activities was close to 1.0 for all diets whereas in the jejunum the ratio of activities is altered by diet. The fact that the jejunal activity ratio was lower than I in fructose-fed rats suggests that the intestine may contain an aldolase with different properties from those in other tissues.

The dietary regulation of the glycolytic enzymes II. Adaptive changes in human jejunum

Abstract The specific effects of dietary sugars on human jejunal glycolytic enzymes were studied in normal volunteers and fasting obese patients. Fructokinase (ketohexokinase, EC 2.7.1.3), Fru- I -P aldolase (ketose- I -phosphate aldehyde-lyase, EC 4.1.2.7), hexokinase (ATP: D -hexose 6-phosphotransferase, EC 2.7.1.1), glucokinase (ATP: D -hexose 6-phosphotransferase, EC 2.7.1.2), and Fru- I ,6-P 2 aldolase (fructose- I ,6-diphosphate D -glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) were measured. Fructose feeding had a specific effect on fructokinase and Fru- I -P aldolase whereas glucose had its major effect on hexokinase and glucokinase. Sucrose gave results intermediate between glucose and fructose. Carbohydrate-free diets gave results intermediate between fasting and carbohydrate diets. There were different responses of the Fru- I -P and Fru- I ,6-P 2 aldolases to different dietary sugars. These data indicate that specific dietary sugars can increase specific jejunal glycolytic enzymes in the human.

The effect of intravenous fructose and glucose on the hepatic α-glycerophosphate concentration in the rat

Abstract The intravenous injection of fructose (200 or 400 mg) into the anesthetized rat leads to a prompt increase in the hepatic α-glycerophosphate concentration. However, this increase is transient since the α-glycerophosphate concentration returns to control levels within 20 min after fructose injection. Analysis of the plasma fructose concentration at this time shows that the fall in the hepatic α-glycerophosphate concentration cannot be due to a lack of substrate for fructokinase (EC 2.7.1.3). The changes in the hepatic pyruvate concentration after intravenous fructose mirrored those for α-glycerophosphate. In comparison to fructose, glucose injection did not lead to an early increase in the hepatic α-glycerophosphate concentration. 20 min after intravenous glucose, the hepatic α-glycerophosphate concentration was nearly 2-fold greater than the control values. The data indicate that the effects of fructose on hepatic fatty acid metabolism cannot be related to sustained increases in hepatic α-glycerophosphate concentration. They also demonstrate that under certain conditions, the hepatic α-glycerophosphate concentration may be greater after glucose than after fructose administration.

Dietary Regulation of Galactose-Metabolizing Enzymes: Adaptive Changes in Rat Jejunum

The effects of dietary galactose, sucrose, fructose, glucose, casein, and fasting upon the activity of four galactose-metabolizing enzymes (galactokinase, galactose-1-phosphate uridyltransferase, uridine diphosphate galactose 4-epimerase, and galactose dehydrogenase) were studied in the jejunum of rats. Galactose produced the greatest increase in enzyme activity, fructose and sucrose produced effects intermediate between galactose and glucose, and casein produced a greater activity increase than fasting, but less than the sugars.

The comparison of the 1-C14-glucose and 6-C14-glucose metabolism of reticulocyte-rich and reticulocyte-poor human red blood cells

consistent with the hypothesis that reticulocytes contain an operative pentose phosphate pathway but not a functioning Kreb’s tricarboxylic acid cycle. I T IS GENERALLY ACCEPTED that the Kreb’s tricarboxylic acid cycle (TCA cycle) is operative in immature nucleated red blood cells but not in mature non-nucleated erythrocytes .I The stage of maturation at which erythroid precursors lose the TCA cycle is not known. The demonstration in mammalian reticulocytes of mjitochondria and certain metabolic intermediates has led to the belief that the TCA cycle functions in human reticulocytes. 1,2 Rapoport and Sarkar 3,4 have shown that rabbit reticulocytes have an appreciably higher isocitric dehydrogenase activity than mature erythrocytes but that reticulocytes have only a slightly higher malic dehydrogenase. Also, Grimes5 showed that the ratio between C1402 from 1-C14-glucose and lactate produced from glucose remained constant in mature erythrocytes and in reticulocyte-rich samples obtained from patients recovering from megaloblastic anemia. This implies that a TCA cycle did not contribute significantly to the glucose metabolism in these reticulocyte-rich samples, otherwise the amount of lactate produced in the reticulocyte preparations would have been reduced proportionately and the C1402 from the 1-C14-glucose would have been raised (since 1-C14-glucose furnishes C1402 from both the pentose phosphate pathway and the TCA cycle), thus altering the ratio as compared to mature erythrocytes. We had the unusual opportunity to measure the utilization of l-C14- and 6-C14-glucose by human reticulocyte-rich preparations obtained from a patient with a mechanical hemolytic anemia with no complicating metabolic process and hence we could test whether or not human reticulocytes metabolize C14-labeled glucose consistent with the presence of a functioning TCA cycle. METHODS