1) Absorption occurs throughout the small intestine. 2) Absorption appears to be saturable, active transport process: thougth to be absorbed as Mn2+; DMT1. 3) Dietary absorption ranges from 1-14%: often 5%, women absorb more than men, absorption decreases when intakes are excessive. 4) Histidine and citrate enhance absorption 5) Fiber, phytate, and oxalate inhibit absorption.
Sources of Manganese
Whole grains, nuts, vegetables, and fruits.
Transport and storage
1) Manganese enters the portal circulation: circulates free (Mn2+) or bound to a alpha-2-macroglobulin; liver clears almost all the newly absorbed Mn. 2) Liver secretion: Free Mn2+; albumin or a alpha-2-macroglobulin bound; transferrin bound (requires oxidation to Mn3+ by ceruloplasmin). 3) Manganese is cleared rapidly from blood and accumulates in the mitochondria: Mediated by a Ca-dependent carrier; Manganese is located in most organs and tissues.
Functions and Mechanisms of Action (biochemical)
1) Enzyme activation and a constituent of metalloenzymes 2) Activation of enzyme-catalyzed reactions.
Functions: activation of enzyme-catalyzed reactions
1) Manganese binds to substrates (ATP) or to the enzyme directly, causes a conformational change that activates the enzyme. 2) Enzymes from several classes require Mn: transferases, hydrolases, oxido-reductases, ligases. 3) Other divalent cations (primarily magnesium or cobalt) can replace the manganese in order to keep the enzymes functioning properly during Mn deficiency.
Functions and Mechanisms of action (metabolic)
1) Normal skeletal growth and development. 2) Essential for glucose utilization. 3) Lipid synthesis and metabolism; cholesterol metabolism. 4) Pancreatic function and development. 5) Prevention of sterility. 6) Important for protein and nucleic acid metabolism. 7) Involved in thyroid hormone synthesis.
1) Xylosyl transferase and glycosyl transferase require Mn. 2) Glycosyl transferase catalyzes the transfer of a sugar moiety (galactose) from uridine diphosphate (UDP) to an acceptor molecule: Proteoglycans, which are important components of bone and connective tissue; Post-translational protein modifications; sugars attached to ser, tyr, thr, (O-linked) or asn (N-linked).
1) Prolidase (Peptidase D: dipeptidase, catalyzes final step in collagen degredation). 2) Arginase (arg + H2O makes Ornithine +urea); elimination of ammonia. 3) Phosphoenolpyruvate carboxykinase (PEPCK): converts oxaloacetate to phosphoenolpyruvate + CO2, essential for gluconeogenesis.
Superoxide dismutase (MnSOD) in mitochondria; similar to Cu/Zn SOD--prevents lipid peroxidation by superoxide radicals.
Pyruvate carboxylase; converts pyruvate to oxaloacetate.
Interactions between manganese and iron
1) High dietary non-heme Fe can reduce both Mn absorption and status in humans and vice versa. 2) Fe and Mn compete for uptake via DMT1. 3) Mn, at high levels, can be stored by ferritin.
1) Unlike Fe, Mn is excreted primarily via bile in the feces. 2) Very little Mn is excreted in the urine and does not increase with excessive dietary intake.
Manganese Deficiency in Humans
It generally does not develop in humans. 1) Mn must be deliberately eliminated from the diet (found mainly in liver, bones, and kidney). 2) Symptoms include: nausea, vomiting, dermatitis, increased serum Ca, P, and alkaline phosphatase, decreased growth of hair and nails, abnormal glucose tolerance.
Manganese deficiency induced in animals
Symptoms include: reduced growth, short crooked leg bones, increased susceptibility to convulsions, delayed sexual maturity; males had testicular degeneration, females delivered stillborn or weak young that suffered from ataxia due to inner ear problems.
Toxicity primarily the central nervous system: 1) First described in 1837 in Chilean Mn Miners. 2) Symptoms include: insomnia, depression, delusions, apathy, anorexia, headaches, anthenia (lower extremity weakness), Parkinson's-like symptoms. 3) Toxicity from dietary intakes has not been described.
Manganese toxicity: Special consideration
Infants fed soy formula: Contains more than 80 times more Mn than BM; liver (excretion) is not mature. In Animal studies, rat and monkeys given Mn resulted in impaired ability to make dopamine; damage to the substantia nigra, caudate, putamen, and globus pallidus; behavioral dysfunction.
Groups at risk for toxicity
welders, railroad and steel workers, and miners; manganese is also present in some pesticides (maneb or mancozeb) , and is a fuel additive (methylcyclopentadienyl Mn tricarboynyl (MMT), anti-knock) in some gasolines.
Exposure in adults to Mn toxicity
has a neurological impact; shuffling gait, shock facial muscles, speech difficulties (including slurred speech), depression and general psychological imbalance: selective dopaminergic dysfunction, neuronal loss and glosis in basal ganglia structures.
Mn is higher in the hair of...
violent felons; children with learning and attention deficit disorders.