---
title: Cycles, a.a.
disqus: hackmd
---
Cycles, a.a.
===
:::success
> Documentation [name=MrDr.Staffan]
###### tags: `page`, `metabolism` `a.a.`
:::

:::info
### Table of Contents
[TOC]
:::
[Top](#Table-of-Contents)

---

# Metabolic Cycle's
[Top](#Table-of-Contents)


---

# Nitrogen

[See separate book page Nitrogen](https://hackmd.io/ArCkz8toQhGjqgrM4CQUQw)

---

# Phosphor

[See separate book page Phosphor](https://hackmd.io/4YTH0e5OSbixap5-w-F-wA)

---

---

## Kelvin cycle (chloroplasts)
[Top](#Table-of-Contents)

Carbon-based life originates from carboxylation that couples atmospheric carbon dioxide to a sugar

Konsumes CO~2~


---

---

# Energizers & oxidative phosphorylation
[Top](#Table-of-Contents)

__the thermodynamic process of transferring energy from one source to another__

This reaction is energetically favourable and releases 30.5 kJ/mol of energy (7.3 kcal)

*lycolysis*
Glucose + 2 NAD+ + 2 Pi + 2 ADP → 2 pyruvate + 2 ATP + 2 NADH + 2 H2O

## Different energy buffering systems
[Top](#Table-of-Contents)

 

      Three digrams showing the same thing.


## Nucleotides
[Top](#Table-of-Contents)

Nucleoside = nitrogenous base + 5-carbon sugar

Nucleoside + phosphate = Nucleotide.

Nucleotides also play a central role in metabolism at a fundamental, cellular level. They carry packets of chemical energy—in the form of the nucleoside triphosphates

Adenosine triphosphate (ATP)
Guanosine triphosphate (GTP)
Cytidine triphosphate (CTP)
Uridine triphosphate (UTP)

& participate in cell signaling
cGMP - cyclic guanosine monophosphate
cAMP - cyclic adenosine monophosphate

Why the two purines are cyclic? They are bigger.

And are the base for co-factors.

Coenzyme A (CoA, SCoA, CoASH)

Flavin adenine dinucleotide (FAD)

## Purines
[Top](#Table-of-Contents)

[See also Neurotransmitters]()

Ref: Disease
[Disorders of purine
and pyrimidine metabolism](https://sci-hub.se/10.1016/B978-0-12-802896-4.00009-2)


### General
[Top](#Table-of-Contents)

What is generating all these?
How these are synthesised would be a main way to regulate energy formation, actual de novo synthesis of the substrates. Or their breakdown.

Metabolism of nucleutides
http://watcut.uwaterloo.ca/webnotes/Metabolism/Nucleotides.html

Overview

Detail: http://watcut.uwaterloo.ca/webnotes/Metabolism/Nucleotides.html

Feedback regulation in purine synthesis

Synthesis of AMP from IMP

Synthesis of GMP from IMP


---

### ATP
[Top](#Table-of-Contents)


ATP synthases that churn out the ATPs that power many cellular processes are driven by gradients in hydrogen ions across membranes

From PPP

#### Binding of metal cations to ATP

#### ATP Synthesis
:::spoiler synthesis
Ribulose adenosine triphosphate

:::

When it reacts with H~2~O it hydrolyses generating energy

Also see Creatine-phosphate (for rapid resynthesis of ATP from AMP)

Catabolise to Adenosine - adenosine
or
Catabolise to Adenosine - Inosine - Hypoxanthine - xanthine -> Uric acid

cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction


---

### IMP
[Top](#Table-of-Contents)

Catabolise to Inosine - Hypoxanthine - xanthine -> Uric acid

---

### XMP
[Top](#Table-of-Contents)

Catabolise to xanthosine - xanthine -> Uric acid

---

### GMP GDP GTP
[Top](#Table-of-Contents)


GTP is essential for signal transduction, especially with G proteins
When bound to GDP, G proteins are inactive.
When a ligand binds a GPCR, an allosteric change in the G protein is triggered, causing GDP to leave and be replaced by GTP

Catabolism
Catabolise to guanosine - guanine - xanthine -> Uric acid

While uric acid is the terminal product of purine degradation in humans and other apes, many other organisms, ranging from fungi to mammals, perform several subsequent reactions that degrade uric acid further to allantoin, which is then excreted.

Urate oxidase (Uricase) = Defective enzyme that makes us not be able to breakdown Uric acid - Genetic advantage. We have a non-functional version.

---

## Pyrimidines
[Top](#Table-of-Contents)


[Disorders of purine
and pyrimidine metabolism](https://sci-hub.se/10.1016/B978-0-12-802896-4.00009-2)

Synthesis of pyrimidines (1)
Degradation

### OMP
[Top](#Table-of-Contents)

### UMP
[Top](#Table-of-Contents)

### CMP
[Top](#Table-of-Contents)

## Deoxy ribonucleotides
[Top](#Table-of-Contents)


## Other Redox reactions
[Top](#Table-of-Contents)

### NADH NAD - Nicotinamide adenine dinucleotide
[Top](#Table-of-Contents)


synthesized from simple building-blocks (de novo) from

the amino acids tryptophan or aspartic acid
Some NAD is converted into the coenzyme nicotinamide adenine dinucleotide phosphate (NADP). The chemistry of __NADP__ is similar to that of NAD, but it has different role, being predominantly a cofactor in anabolic metabolism

De novo synthesis
adenine
Nicotineamide

tryptophan (Trp)
quinolinic acid (QA)
nicotinic acid mononucleotide (NaMN)
nicotinic acid adenine dinucleotide (NaAD)
nicotinamide (Nam)

Non-redox roles
* Consumed by SIRTS (NAD-dependent deacetylases),
* [ADP-ribosylation](https://en.wikipedia.org/wiki/ADP-ribosylation)
* post translational modification
* precursor of cyclic ADP-ribose (calcium signaling)
* [Transmittor substance](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031738)

### FMN FAD FADH FADH~2~
[Top](#Table-of-Contents)

Riboflavin - Vitamin B2

Flavin mononucleotide


flavin adenine dinucleotide (FAD)

FAD has a more positive reduction potential than NAD+ and is a very strong oxidizing agent

Reaction of the __flavin group__ of FAD to form FADH2

Flavoproteins = 60% linked to human disease
redox cofactors

have either an FMN or FAD molecule as a prosthetic group, this prosthetic group can be tightly bound or covalently linked. Only about 5-10% of flavoproteins have a covalently linked FAD, but these enzymes have stronger redox power

There are many flavoproteins besides components of the succinate dehydrogenase complex, including α-ketoglutarate dehydrogenase and a component of the pyruvate dehydrogenase complex

Carbon-nitroge - Monoamine oxidase (MAO) is an extensively studied flavoenzyme due to its biological importance with the catabolism of norepinephrine, serotonin and dopamine

redox cofactors

FMO1 high in astro
the others low.

Other flavoproteins
LDHD d-lactate dehydrogenase
GPD2 Glycerol 3-phosphate dehydrogenase
CHDH Choline dehydrogenase
L2HGDH l-2-Hydroxyglutarate dehydrogenase
D2HGDH d-2-Hydroxyglutarate dehydrogenase
AOX1 - astro (mouse)
DPYD - oligo (mouse)
DHCR24 - astro + oligo
ACOX1 - AcylCoA oxidase - astro (human)
ACOX2
C7orf10 - astro (low)
ACADL astro (mouse)
ACADVL astro (human)
Nphp3 - astro (mouse)
MAOA Monoaminoxidase astro (human)
MAOB Monoaminoxidase astro
PIPOX - astro - Sarcosine related
SMO - mostly astro
SARDH - also astro Sarcosine related
PRODH - Astro - Prolinedehydrogenase
NQO1 - NAD(P)H Quinone Dehydrogenase 1

SQLE - astro in mouse also in OPC neurons - Squalene epoxidase catalyzes the first oxygenation step in sterol biosynthesis and is thought to be one of the rate-limiting enzymes in this pathway. Protein atlas suggest astrocytes.


STEAP3 - Iron reduction astro mouse
CRY2 - FAD-binding DNA-photolyase (astro+neurons mouse) circadian core oscillator complex. See [Circadian clock](#CircadianClock)

MICAL1 Axon guidance protein - all + Astro
MICAL2 Axon guidance protein - astro and neurons
MICAL3 Axon guidance protein - OPC lineage
MICALL1 - Oligo(mouse)
MICALL2 - Astro + endothelial (mouse)

Slc52a3 - C20orf54 / Riboflavin transporter

RFTN2

### Creatine Creatinephosphate
[Top](#Table-of-Contents)

# Lactate
[See Lactate page](https://hackmd.io/pppAihCtQOCwPq5J1Fu0VQ)

# Glucocorticoids
[Top](#Table-of-Contents)

# Sympathetic-Adreno-Medullar (SAM) axis
[Top](#Table-of-Contents)

# Hypothalamus-Pituitary-Adrenal (HPA) axis
[Top](#Table-of-Contents)

# Src Kinases
[Top](#Table-of-Contents)

# Sarcosine
[Top](#Table-of-Contents)

# Coenzyme Q10 (ubiquinol, ubiquinone)
[Top](#Table-of-Contents)

It is a component of the electron transport chain and participates in aerobic cellular respiration, which generates energy in the form of ATP

# Vitamin K?
[Top](#Table-of-Contents)

# CircadianClock
[Top](#Table-of-Contents)

Many genes from this mechanisms seems to be expressed in astrocytes.

circadian core oscillator complex

Per 1 - mostly mouse Astro +neurons
Per 2 - human astro
Per 3 - mouse astro
CRY1 - Human+mouse not entirely specific
CRY2 - astro
NPAS2
ARNTL
ARNTL2 - low
NR1D1 (astro) & NR1D2 (var cells) - nuclear receptors NR1D1/2
RORA - astro+neurons
RORB astro

Clock
# Wood-ljundal pathway
https://en.wikipedia.org/wiki/Wood%E2%80%93Ljungdahl_pathway

# Free energy - Gibbs free energy - Free Enthalpy - G
[Top](#Table-of-Contents)

"Available energy" [name=Josiah Willard Gibbs] 1873
distinguished from Helmholtz free energy.

thermodynamic potential that can be used to calculate the maximum of reversible work that may be performed by a thermodynamic system at a constant temperature and pressure (isothermal, isobaric)

decrease in Gibbs free energy equals the work done by the system to its surroundings, minus the work of the pressure forces

Enthalpy - a thermodynamic quantity equivalent to the total heat content of a system. It is equal to the internal energy of the system plus the product of pressure and volume.

Entropy is commonly associated with the amount of order, disorder, or chaos in a thermodynamic system.

In recent years, in chemistry textbooks there has been a shift away from using the terms "order" and "disorder" to that of the concept of __energy dispersion__ to describe entropy

__"The entropy of the universe tends to a maximum"__

"Entropy-driven order"

:::info
Acidosis too much lactate or rather lactic acid. Is a lack of electrons?

Driving force of evolution? Well what drives a bacteria to eat and divide? What drives a human to want to have children or go up in the morning. Food. The excess of energy in unsatisfied atoms. They want to become stable. Low entropy.

They react with each other in chasing this perfect balance. depending on their absolute environment they lean towards energy balance by reacting with each other. All atoms in a reasonably isolated system does this. This is the Idea of Gaia. No peak in entropy (no reactive compounds - no life. Entropy peaks can be explained in several ways e.g. crystal formation.

Earth recive high entropy heat and emitts low entropy radiation. Doing this is bounce off/ pass through earth compounds. This fuel reactions on earth.

The input of energy
* "Laser-ish rays sun"
* cooling off of the planet (Incl. radioactive decay in crust)
* Planet core fission - Thorium-U233 (debated)
* impacts
* Moon gravity
is the driving force of "evolution" or change over time.

Evolution is the path the dissipation of energy takes.
Microorganisms are predisposed to dissipate the energy in their diet/intake/interaction in the most efficient way. Creating copies of one self iterating this interaction over time, constitutes efficient dissipation.
Apes dont crave sugar to be able have kids. They are predisposed to take in high amounts of energy and spread it. Complexity and structure acts as an enzyme of energy dissipation.
:::