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Figure 2. Gluconeogenesis.

Manganese is known to play a key role in free radical control via its involvement in the Manganese SOD enzyme, and it is required by the glycosyl transferases for participation in the formation of cartilage and other connective tissues. What about its role in glucose and carbohydrate metabolism? Dr. Deborah L. Baly, et al. did several animal studies concerning manganese and its role in this area. Dr. Baly’s studies found that manganese deficiency lead to altered carbohydrate metabolism at the level of pancreatic insulin synthesis and gluconeogenesis. Further studies by M.L.White have recognized that the insulin receptor was a hormone dependent kinase that can be stimulated by Mg and Mn, and that manganese activates the insulin receptor protein kinase in vitro via an effect on Mg ATP. M. Ueda, et al., demonstrated that manganese can enhance extracellular binding of insulin to its receptor, facilitates the physiological actions of insulin and mimics the action of the hormone. Manganese deficiency was seen to result in a decrease in the number of glucose transporters in adipose tissue. Baly, et al also have observed that manganese deficient animals had a seven fold lower proinsulin mRNA, resulting in a decreased insulinogenesis. However, it is the actions of the manganese metalloenzyme pyruvate carboxylase and the phosphoeneolpyruvate carboxykinase, a manganese-activated enzyme in the initiation of gluconeogenesis that may be the most key role of manganese in glucose homeostasis (see Fig. 2). Cellular manganese concentration is a key factor in the regulation of carbohydrate metabolism, and plays a role in gluconeogenesis as well.

ZincFigure 3. Zinc's hold on oxygen in stablizing carboxypeptidases.

Zinc is without question the most talked about of all the immune supportive nutrients, and its role in healing and dermal health is also well known. In addition, it plays an important role in food digestion and absorption. Zinc is an essential cofactor for carbonic anhydrases, proteases, phosphatases and other enzymes involved in the digestion and absorption of food. Carbonic anhydrases work in the production of gastric acid. The carboxypeptidases, which are stabilized by zinc, are zinc dependent digestive enzymes from the pancreas (see Fig. 3). Several peptidases of the intestinal brush border are zinc enzymes, including leucine aminopeptidase, membrane alanine aminopeptidase, glutamyl aminopeptidase, membrane dipeptidase, and a few others. Another brush border zinc enzyme is a form of carboxypeptidase that is needed to cleave off gamma-glutamyl residues from dietary folate prior to absorption. An alkaline phosphatase that requires both zinc and magnesium works at the intestinal brush border to digest complex forms of thiamine, riboflavin and pantothenate. Zinc deficiency is known to result in the impairment in the ability to absorb water and electrolytes, and is a trigger for diarrhea. The gastrointestinal tract may be the first target areas where zinc insufficiency is manifested.