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# System prepended metadata

title: Collagen
tags: [page, collagen]

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title: Collagen
disqus: hackmd
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Collagen
===
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> Documentation [name=MrDr.Staffan]
###### tags: `page`, `collagen`
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### Table of Contents
[TOC]
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[Top](#Table-of-Contents)

**Why this page?**
Many associated genes seem to be cell type specific. Astrocytes as modulators of collagen?

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[Also see ECM](https://hackmd.io/@sholmqvist/BJpKurTBB/%2Fc7UkEUBYT26RS-oIC2bVZA)
**General**
main structural protein in the extracellular matrix in the various connective tissues in the body


Hydroxylation of Proline leads to  a 16dC decrease in melting temperature of hydroxylation.

Co2-N-H20_FA-Lipids-Sugars-Nucleobases-A

# BioXive

https://www.biorxiv.org/content/10.1101/2022.03.04.482898v1.full
![](https://hackmd.io/_uploads/rJbBSOBWT.png)



# Formation
![](https://i.imgur.com/PxA08l3.png)
[![](https://i.imgur.com/N21bcYL.png)](https://sci-hub.hkvisa.net/10.1002/mas.21600)


As the main component of connective tissue, it is the most abundant protein in mammals,[1] making up from 25% to 35% of the whole-body protein contentI am - wiki
(filaments are biochemical emergent structures. While collagen is a very simple proline based superstructure, formed from Vast excess Of small repetitive compound proline. 
Microtubules and Actin is much much larger, Therefore they are likely first formed by excess of small proteins.
Emergent structures from more  poly(mixed)peptide

Excess of a particular compound, peptide, protein Is handled by the cell.
1. Rid yourself, secretion of the compound. Problem for others, but not for a single cell. = problems in multicellular life.
(Sugars as they are difficult to Contain, and largely affect turgor) 


2. Metabolise, yes most compounds can be metabolized, but some are easier than others. E.g. Reduced carbon in SFU and UFA readily can be oxidizEd and anaplerotically Contribute to the TCA. 

Glycine on the other hand can not easily be broken further down. The N and COoH too close togheter for any enzyme to get a good "grip". Not because it hasn't bothered to evolve... Wasn't functional, but instead because there seem to be a mechanical limit to molecular metabolism. Certain boundaries of what is functionally possible.


4.Sequestering. 
5. 
6.
Sequestering of (non-useful Or excess metabolites).

Any, nh2-ch(r)-COO
are sticky, I they form two dimensional crystals. I.e. Peptides/simple proteins.
Polypeptides

Forming an internal crystal creates a regional loW Tension energystructure. This increase the entropy IN the rest of the system.
(when a part of the system becomes more ordered other parts must be disordered to maintain the basic summed state of the system.

By forming and breaking apart filaments/Kvasicrystals - the cell can influence tge metabolic flow.

This might nicely fits the matter of prokaryote (and sperm) having Single cilia. 
What if the cilias original molecular function was as a structure Acting as an enthalpy generator (local order) by growing this cilia. Meaning a negativ vacuum Of Entropy is needed elsewhere in the system, thus a flow of metabolism is Driven by, with one pole being the growing structure enthalpy. And another parallelled entropic force elsewhere or everywhere in the cell. A local source of entropy. 

If we build an orderly house, we must also have an uNorderly Pile of bricks to build it from. This pile has to be extracted from some other External order / mudpit. 
And the overall grow in entropy is always true. That means the more orde you want locally, I the more disorder it creates on the fringes. If it is not, then a tension in the system builds up. Just like heated water builds in a closed vessel. Metabolic switches and release outlets are in place to manage this. 

[these things start to really sound like human activity] 


[does the origin of numBers/logic we can grasp Lie in chemistry carbon and bindings? Would the "choices" done there propagate as a fractal up to Phenotypes we se today.?] 

I my view this could be accomplished if the basic function of cilia is to bit by bit shedd its tip into it's surrounding. 

The Propulsion cilia Can give is then A secondavhry emergent function of the cilia, an unforseen consequence. 


(buffering enthalpy (order). (just like oil or diamond is a system resulting from squeezing (carbon) into order.

this order is very unnatural and can give loads of energy when it's equilibrium with the surroundings is Equalised. 

If so such crystalS of enthalphy can be used to regulate the metabolic flow of the system - with some activation energy, this Buffered enthaloy can be released in the form of

Plants lower their internal entropy by growing. They expand their immobile structure in order to maintain metabolic flow.

Does all multicellular life grow? ⁴in size. 

# Aminoacids
[Also see Glycine & Proline](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F6boDt7fZRfmxzsr9k2HIgg#Proline)

Every third is Glycine




# Genes
[See Proline](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F6boDt7fZRfmxzsr9k2HIgg#Proline)

[See Glycine](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F6boDt7fZRfmxzsr9k2HIgg#Glycine)

![](https://hackmd.io/_uploads/ryI7ac2kT.png)


Prep Plod1 Plod2 Plod3 p3h1 p3h2 p3h3 p3h4 P4ha1 P4ha2 P4ha3 P4hb
P4htm fkbp1A Fkbp1B Fkbp2 Fkbp3 Fkbp4 Fkbp5 Fkbp6 Fkbp7 Fkbp8 Fkbp9 Fkbp10 Fkbp11 Fkbp14 Fkbp15 

Crtap
Cacybp
lox
loxl1 loxl2 loxl3 loxl4
Colgalt1
Colgalt2
![](https://i.imgur.com/cx10wlG.png)

![](https://i.imgur.com/Z1fwWA8.png)



## Prep
Prolyl Endopeptidase
Neutrophils contain prolyl endopeptidase and generate the chemotactic peptide, PGP, from collagen.


## Plod
[See Dioxygenases](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FLLM5drPYRpaHsNk6M11lqw#Dioxygenase-EC-11311)

Procollagen Lysyl Hydroxylase // Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase

**Hydroxylation of lysyl** residues in **collagen-like peptides**
resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular **crosslinks**

membrane-bound homodimeric protein localized to the cisternae of the endoplasmic reticulum.

Cofactors iron and ascorbate.

**Plod1** Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 1

**Plod2** // LH2
a key regulator of collagen cross-linking stability
The FKBP65-LH2-complex promotes dimerization of LH2 and thereby positively modulates its activity (Gjaltema et al., 2016; Chen et al., 2017).

**Plod3**

Ehlers-Danlos Syndrome, Kyphoscoliotic Type, 1

## p3H Prolyl 3-Hydroxylase 1
[See Dioxygenases](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FLLM5drPYRpaHsNk6M11lqw#Dioxygenase-EC-11311)

Prolyl 3-Hydroxylase 1 // "Growth Suppressor 1"

p3h1
localized to the endoplasmic reticulum and their activity is required for **proper collagen synthesis and assembly**

collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.

p3h2
proline 3-hydroxylation of collagen COL4A1 (high) and COL1A1 (low).

p3h3
Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains

p3h4
(Inactive) 


P4HA1 Prolyl 4-Hydroxylase Subunit Alpha 1
In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper **three-dimensional folding** of newly synthesized procollagen chains

P4ha2
pathways are Collagen chain trimerization and Extracellular matrix organization
P4ha3
pathways are Collagen chain trimerization and Extracellular matrix organization

P4hb
related pathways are Translational Control and Metabolism of proteins

P4htm
Hypotonia, Hypoventilation, Impaired Intellectual Development, Dysautonomia, Epilepsy, And Eye Abnormalities and Dysautonomia.
hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A.
May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation
May be involved in the **degradation of HIF TFs under normoxia**

## Fkbps
FK506 Binding Protein // Peptidyl-Prolyl Cis-Trans Isomerase
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290070/
FKBPs are present in all eukaryotes, ranging from yeasts to humans, and expressed in most tissues. Mammalian FKBPs can be subdivided into four groups: the cytoplasmic, endoplasmic reticulum, nuclear, and TPR (tetratricopeptide repeats)-containing FKBPs

Fkbps and collagen
Ishikawa et al. investigated the role of endoplasmic FKBPs as chaperones for collagen biosynthesis. Since **collagen** contains multiple proline residues, the **cis-trans isomerization of proline** is thought to be the **rate-determining** step during triple-helix formation.



fkbp1A // Fkbp12 Prolyl Isomerase 1A
 
Fkbp2 // Fkbp13
Fkbp5 // Fkbp51
Fkbp10 // Fkbp65 Associated with Plod2

# Collagen types
![](https://i.imgur.com/C7z4u2O.png)
<br><br>
---
<br><br>
![](https://i.imgur.com/MNSgrSz.png)


## MACITs Col13 Col23 Col25
Membrane collagen types XIII, XXIII, and XXV are also collectively referred to as membrane-associated collagens with interrupted triple helices (MACITs)


## Angiogenesis Collagens
[![](https://i.imgur.com/Kp0N0nS.png)](https://sci-hub.hkvisa.net/10.1002/mas.21600)
Col4a1
Col4a2
Col4a3
Col15a1
Col18a1



# Collagen and synapses

## Col19a1
Collagen XIX, although initially identified as a fibrilassociated collagen with interrupted triple helices (FACIT) by sequence analysis (Khaleduzzaman et al., 1997), does not appear to bind collagen fibers but rather accumulates in the extracellular matrix (ECM) of restricted tissues, including neural tissue (Myers et al., 1997; Sumiyoshi et al., 1997, 2001

[2010. J Comp Neurol.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913722/)