In a tendon the greater part of the dry mass comes not from cells but from the material between them. Depending on tissue and age, sixty to eighty per cent of this dry mass is fibrous protein, the rest water binding, sugar chains and a comparatively small cellular share. The cells therefore produce a material in which they subsequently appear only as inclusions.
This material arises in two separate stages. One takes place inside the cell: chains are read off, folded and fitted with sugar residues before they leave the cell interior. The other only begins outside, when individual molecules become a load-bearing fibre. Copper and manganese appear at different points in these two stages — and the European Union carries a separate, individually worded line for each of the two elements.
Apatitkluft is an editorial text offering on this subject. This page summarises what the fully written-out edition presents at length; only what is set down word for word in the annex to Regulation (EU) No 432/2012 is quoted.
Scientific facts on 2 minerals — in line with EU Regulation (EU) No 432/2012
To the summaryThe two trace elements occur at different stations of the same process. That is why they stand here one after the other, each with the figures that can be substantiated for it, and with the one wording that the European Union assigns to it.
Copper switches between two charge states and is used in enzymes that turn over oxygen for exactly that reason. In the body it is measured almost only in bound form — in blood plasma attached to a large transport protein, in tissues to the enzymes themselves. An adult's total stock runs to a few dozen milligrams.
For the fibrous material between the cells a single copper-containing enzyme matters, and it only works where the cell has already released its product. The wording authorised for this in the European Union is tied to the element copper and applies to no other:
Under Regulation (EU) No 432/2012
| Symbol | Cu |
|---|---|
| Atomic number | 29 |
| Classification | Trace element |
| Labelling reference value | 1 mg per day |
| Stock in the body | 70–100 mg |
| Significant amount per 100 g | 0.15 mg |
An adult carries around ten to twenty milligrams of manganese, the greater part of it in liver, kidney and bone tissue. Only a small fraction of what arrives with food is absorbed; the balance runs through excretion with the bile and not through the kidney.
The enzymes that call for this ion sit predominantly inside the cell: at the membrane stacks where sugar residues are attached, and in the interior of the mitochondria. For manganese too the European Union carries a line of its own, which is read separately from the previous one:
Under Regulation (EU) No 432/2012
| Symbol | Mn |
|---|---|
| Atomic number | 25 |
| Classification | Trace element |
| Labelling reference value | 2 mg per day |
| Stock in the body | 10–20 mg |
| Significant amount per 100 g | 0.30 mg |
The figures in the side panels describe elements and label values. The two sentences quoted remain separate and are not drawn together into a joint statement.
Three sections pick out what can be quantified about this tissue and at which two points the two elements occur in it. They do not build on one another.
The basic molecule consists of three amino acid chains wound around one another. So that the three strands can lie this closely together, the smallest of all building blocks, glycine, sits at every third position. The finished rod measures about 1.5 nanometres in diameter and around 300 nanometres in length — a ratio of roughly one to two hundred.
Outside the cell these rods lie against one another in staggered fashion. The offset is always the same size and produces, under the electron microscope, a regular pattern of light and dark bands with a period of around 67 nanometres. Such strands become fibres, fibres become bundles, bundles become a tendon: six orders of magnitude lie between the individual molecule and the component that holds a joint.
Details of the geometry of the tissue follow materials-science and histological literature. No health-related statement arises from this.
The copper-containing enzyme of this tissue is exported from the cell as a precursor and only trimmed to size outside. It does not bring its catalytically active group with it from outside: that group arises from two side chains of its own molecule, a tyrosine and a lysine, which combine into a quinoid structure. This conversion only takes place after a copper ion has been inserted.
The element therefore sits in an unusual place. Most metalloenzymes work inside the cell; this one works where no cell stands any longer, namely in the material itself. It is to this relationship that the entry the European Union carries for copper refers. It reads, unaltered: „Copper contributes to the maintenance of normal connective tissue“ — Under Regulation (EU) No 432/2012.
Before a chain leaves the cell, galactose and glucose are attached at individual positions. The transfer enzymes responsible for this hold a doubly positively charged manganese ion in their binding pocket; it serves to hold the delivered sugar unit in position and is not consumed in the reaction. The long sugar chains of the water-binding ground substance also arise at these membrane stacks.
A second manganese-containing enzyme stands further upstream in metabolism: it splits arginine and thereby supplies the precursor from which the cell makes proline — the amino acid that occurs particularly frequently in the triple helix. For manganese the Union list carries a line of its own: „Manganese contributes to the normal formation of connective tissue“ — Under Regulation (EU) No 432/2012.
This section describes enzyme reactions. Anyone deriving from them an effect on the course of a disease goes beyond what the two lines quoted support — they are addressed to the general population.
This page reproduces the structure; the file gives the derivation to go with it — with a scale bar on every figure, the complete analytical columns for both elements and a list of the specialist literature consulted.
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