Manganese Abstracts 7


Studies On Manganese Deficiency In The Rat
            (Boyer et al., 1942) Download
Pronounced manganese deficiency in the rat has been produced by use of rats weaned without access to manganese. This deficiency resulted in definitely impaired growth in the male and the female rat. In the manganese-deficient female rat estrous cycles were irregular or absent, and there was a marked delay in the opening of the vaginal orifice. A manganese deficiency in the male rat caused testicular degeneration and complete sterility due to lack of spermatozoa production. Both male and female manganese-deficient rats were unable to reproduce. No histological abnormalities were detected in the adrenal, kidney, pituitary, and thyroid of the manganese-deficient rat. The deficiency did not result in reduced ascorbic acid content of tissues, nor did ascorbic acid stimulate the growth of the manganese-deficient rat. Synthesis of ascorbic acid from mannose by rat liver and other tissues in vitro could not be obtained with or without added manganese. A reduced arginase concentration in the liver of the manganese-deficient rat was found. There were no essential differences in the activity of the intestinal dipeptidases studied.

Microdetermination of manganese in biological material by a modified catalytic method.
            (Fore and Morton, 1952) Download
A procedure for the determination of amounts of manganese is described. The method cannot be applied to the determination of manganese in bone, nor, without further study, to manganese in blood.

Impaired manganese metabolism causes mitotic misregulation.
            (García-Rodríguez et al., 2012) Download
Manganese is an essential trace element, whose intracellular levels need to be carefully regulated. Mn(2+) acts as a cofactor for many enzymes and excess of Mn(2+) is toxic. Alterations in Mn(2+) homeostasis affect metabolic functions and mutations in the human Mn(2+)/Ca(2+) transporter ATP2C1 have been linked to Hailey-Hailey disease. By deletion of the yeast orthologue PMR1 we have studied the impact of Mn(2+) on cell cycle progression and show that an excess of cytosolic Mn(2+) alters S-phase transit, induces transcriptional up-regulation of cell cycle regulators, bypasses the need for S-phase cell cycle checkpoints and predisposes to genomic instability. On the other hand, we find that depletion of the Golgi Mn(2+) pool requires a functional morphology checkpoint to avoid the formation of polyploid cells.

The role of pyridoxal and manganous ions in the synthesis of iodothyronines.
            (Karmarkar and Stanbury, 1967) Download
I. The synthesis of 3,3' diiodothyronine (3,3'T2) from monoiodotyrosine (MIT) in an assay system containing MIT, pyridoxal, Mn2+, thyroid microsomes, and a HzOz-generating system was studied. The yield of 3,3'T2 was approx. 17 To and was only slightly less if the microsomes were preboiled for 20 min. 2. Omission of microsomes from the assay system and chromatography of a butanol extract of the system in butanol-acetic acid-water disclosed a component with RE 0.8 in 15 % yield. The formation of this component depended on the presence of Mn~+, MIT, and pyridoxal. Spectral analysis and other data indicated that it is a metal chelate of Mn2+with a Schiff base formed from pyridoxal and MIT. This metal chelate exhibits peroxidase activity which may be primarily responsible for the synthesis of 3,3'Tz from MIT in the system studied.

Principal Mineral Elements In Nutrition
            (Macy, 1942) Download
In a consideration of the mineral constituents of the body, one should bear in mind that, while these elements constitute only a small portion of the body weight, they enter into all the activities of the body to a much greater degree than their mere weight would indicate. For many years the important dietary components were stated to be protein, fat and carbohydrate, with slight emphasis placed on water and minerals; later, vitamins were added as necessary adjuncts. In the last few years, however, through voluminous records of physiologic investigations, the mineral elements have come into prominence and are now recognized as essential participants in practically every metabolic process carried on by the body.

Vitamin B(1) and cocarboxylase in animal tissues.
            (Ochoa and Peters, 1938) Download
Vitamin B1 (as also does its monophosphoric ester) stimulates the de-carboxylation of pyruvic acid by alkaline washed yeast in the presence of cocarboxylase. Mn++ greatly stimulates the carboxylase system if present in sufficient concentrations. Administration of vitamin B1to animals leads to an immediate accumulation of both vitamin B1 and its pyrophosphoric ester in the liver. For the first time this brings the liver into prominence in the metabolism of vitamin B1.

Metabolic Interdependence of Vitamin B1 and Manganese. Reciprocal Neutralization of Their Toxic Effects.
            (Perla and Sandberg, 1939) Download
In rats fed normal adequate diets an excess of vitamin B1 in amounts exceeding 30 or 40 times the minimal requirement results in an interference with the capacity of the mother to rear her young and with the nursing instinct. The toxic manifestations of an excess of vitamin B, were found to be dependent on the ratio of manganese to vitamin B, in the diet. The addition of manganee to the diet in amounts of 2 mg per rat per day completely neutralized the unfavorable effects of the excess of vitamin B, (400 gamma daily).

The Prevention Of Toxic Manifestations Of An Excess Of Vitamin B1 By Supplements Of Manganese To The Diet.
            (Perla, 1939) Download
These results demonstrate that manganese is essential in the utilization of vitamin B1 in the tissues and is intimately bound up mith the role of vitamin B1 in the physiology of the organisms. It also suggests that variations in certain constituents of the diet, such as manganese, may greatly affect the vitamin B1 requirement. With the use of large amounts of vitamin Bl in therapy, an adequate supply of manganese must be made available.

Thyroid and vitamin B(1).
            (Peters and Rossiter, 1939) Download
In confirmation of the work of others subcutaneous injection of vitaminB1 gives protection from the loss in weight produced in rats by thyroxine injections. A pretreatment with vitamin B1 also lessens the rate at which thyroid fed rats fall in weight. Injection of vitamin B1 increases the cocarboxylase content of the tissues of both normal and hyperthyroid animals. After 7 days of pretreatment with vitamin B1 the cocarboxylase content ofthe tissues falsmore rapidly in hyperthyroid than in normal animals.

The Mineral Basis Of Life.
            (Sheldon, 1934) Download
It is now recognized that the original list of the constituents of protoplasm (C, H, 0, N, S, P, Na, Ca, K, Mg, Cl, I, Fe) must be widely extended. It is clear that, as Bertrand has said, the body cannot be regarded as a democracy, but rather as an oligarchy, in which a large amount of passive elements are ordered and governed by minute amounts of active ones, and the biological investigation of these very active elements cannot but be fruitful.

Handbook Of Nutrition: IX: The Trace Elements In Nutrition
            (Shils, 1942) Download
The many mineral elements which exist in animal tissues occur in widely varying amounts. They range from calcium, which comprises approximately 2 per cent of the adult human body weight and which can be expressed in kilograms, down to those which we must measure in milligrams and even micrograms, and which have been termed" trace elements." The dividing line between trace and non-trace elements is purely arbitrary and a matter of choice.

Interrelations between essential metal ions and human diseases BOOK
            (Sigel et al., 2013) Download
It is an old wisdom that metals are indispensable for life. Indeed, several of them, like sodium, potassium, and calcium, are easily discovered in living matter. However, the role of metals and their impact on life remained largely hidden until inorganic chemistry and coordination chemistry experienced a pronounced revival in the 1950s. Most of the 13 metals and 3 metalloids and their ions, which are covered in this volume, have been proven to be essential for humans. Indeed, it is an old wisdom that metal ions are indispensable for life. The main group metals, i.e., sodium, potassium, magnesium, and calcium, belong to the so-called bulk elements, and they occur in humans (70 kg) between about 20 g (Mg) and 1000 g (Ca)

Manganese and the brain.
            (Tuschl et al., 2013) Download
Manganese (Mn) is an essential trace metal that is pivotal for normal cell function and metabolism. Its homeostasis is tightly regulated; however, the mechanisms of Mn homeostasis are poorly characterized. While a number of proteins such as the divalent metal transporter 1, the transferrin/transferrin receptor complex, the ZIP family metal transporters ZIP-8 and ZIP-14, the secretory pathway calcium ATPases SPCA1 and SPCA2, ATP13A2, and ferroportin have been suggested to play a role in Mn transport, the degree that each of them contributes to Mn homeostasis has still to be determined. The recent discovery of SLC30A10 as a crucial Mn transporter in humans has shed further light on our understanding of Mn transport across the cell. Although essential, Mn is toxic at high concentrations. Mn neurotoxicity has been attributed to impaired dopaminergic (DAergic), glutamatergic and GABAergic transmission, mitochondrial dysfunction, oxidative stress, and neuroinflammation. As a result of preferential accumulation of Mn in the DAergic cells of the basal ganglia, particularly the globus pallidus, Mn toxicity causes extrapyramidal motor dysfunction. Firstly described as "manganism" in miners during the nineteenth century, this movement disorder resembles Parkinson's disease characterized by hypokinesia and postural instability. To date, a variety of acquired causes of brain Mn accumulation can be distinguished from an autosomal recessively inherited disorder of Mn metabolism caused by mutations in the SLC30A10 gene. Both, acquired and inherited hypermanganesemia, lead to Mn deposition in the basal ganglia associated with pathognomonic magnetic resonance imaging appearances of hyperintense basal ganglia on T1-weighted images. Current treatment strategies for Mn toxicity combine chelation therapy to reduce the body Mn load and iron (Fe) supplementation to reduce Mn binding to proteins that interact with both Mn and Fe. This chapter summarizes our current understanding of Mn homeostasis and the mechanisms of Mn toxicity and highlights the clinical disorders associated with Mn neurotoxicity.



Boyer, P.D., J.H. Shaw, and P.H. Phillips (1942), ‘Studies On Manganese Deficiency In The Rat’, J. Biol. Chem., 143 417-25. PubMed:
Fore, H and RA Morton (1952), ‘Microdetermination of manganese in biological material by a modified catalytic method.’, Biochem J, 51 (5), 594-98. PubMed: 13018130
García-Rodríguez, N, et al. (2012), ‘Impaired manganese metabolism causes mitotic misregulation.’, J Biol Chem, 287 (22), 18717-29. PubMed: 22493290
Karmarkar, MG and JB Stanbury (1967), ‘The role of pyridoxal and manganous ions in the synthesis of iodothyronines.’, Biochim Biophys Acta, 141 (3), 483-91. PubMed: 6049512
Macy (1942), ‘Principal Mineral Elements In Nutrition’, JAMA, 120 (1), 34-42. PubMed:
Ochoa, S and RA Peters (1938), ‘Vitamin B(1) and cocarboxylase in animal tissues.’, Biochem J, 32 (9), 1501-15. PubMed: 16746779
Perla, D (1939), ‘The Prevention Of Toxic Manifestations Of An Excess Of Vitamin B1 By Supplements Of Manganese To The Diet.’, Science, 89 (2302), 132-33. PubMed: 17781204
Perla, David and Marta Sandberg (1939), ‘Metabolic Interdependence of Vitamin B1 and Manganese. Reciprocal Neutralization of Their Toxic Effects.’, Proc Soc for Exp Biology and Medicine, 41 (2), 522-27. PubMed:
Peters, RA and RJ Rossiter (1939), ‘Thyroid and vitamin B(1).’, Biochem J, 33 (7), 1140-50. PubMed: 16747014
Sheldon, JH (1934), ‘The Mineral Basis Of Life.’, Br Med J, 1 (3810), 47-53. PubMed: 20777999
Shils, ME (1942), ‘Handbook Of Nutrition: IX: The Trace Elements In Nutrition’, JAMA, 120 (8), 609. PubMed:
Sigel, A, H Sigel, and R Sigel (2013), Interrelations between essential metal ions and human diseases, (Metal Ions in Life Sciences, 13; Springer).
Tuschl, K, PB Mills, and PT Clayton (2013), ‘Manganese and the brain.’, Int Rev Neurobiol, 110 277-312. PubMed: 24209443