---
title: Amino Acids
disqus: hackmd
---
Amino Acids
===
:::success
> Documentation [name=MrDr.Staffan]
###### tags: `page`, `amino_acids`
:::

Aminoacids are the ash of the metabolic fire. [The TCA]

In the oxidation of carbon, Nitrogen carboxy acids are the smallest possible, that are difficult to fully oxidize. Clumping togheter, forming the matter of the cell.


Small side chains are more common? over represented in protein amino acids?

Bigger chains would not get into mitochondria.

Where does the aminoacid-interconversion of the cell happen?

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

**Why this page?**
Because they are smaller than nucleotides and each individual is a chemical building block & metabolite at once.

---

# Concentration of aminoacids in cellular compartments
Concentration of amino acids in the cytoplasm is relatively high, typically ranging from 1 to 20 millimolar (mM) or even higher for some amino acids.

Most compartments are similar to the cytoplasm (nuc. ER. Golgi.)

Lysosomes & Peroxisomes are typically lower than cytoplasm?

Mitochondria is low range of 0.1 to 2 mM.

[Need references for these]


[Top](#Table-of-Contents)

# early chemistry
[See Everything entropy - early chemistry]

However, many have hypothesized that before the advent of cellular life, amino acids must have been generated from completely different precursors, aldehydes, rather than α-keto acids, since enzymes to carry out the conversion did not yet exist. But that idea has led to debate about how and when the switch occurred from aldehydes to α-keto acids as the key ingredient for making amino acids.

https://dx.doi.org/10.1038/s41557-022-00999-w

https://phys-org.cdn.ampproject.org/v/s/phys.org/news/2022-07-scientists-life-chemical-reactions.amp?amp_gsa=1&amp_js_v=a9&usqp=mq331AQIKAGwASCAAgM%3D#amp_tf=From%20%251%24s&aoh=16593509679205&csi=0&referrer=https%3A%2F%2Fwww.google.com&ampshare=https%3A%2F%2Fphys.org%2Fnews%2F2022-07-scientists-life-chemical-reactions.html

# AA distribution



Percentages of amino acids in human collagen I. Amino acid composition of (a) collagen proteins and (b) non-collagen proteins in human lung (Bradley et al. 1974). While glycine and proline/hydroxyproline make up 33.37% and 20.51% of total amino acid residues in collagens, their percentage is much lower in other proteins.



# Essential


Nine amino acids—histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine—are not synthesized by mammals
Only left

# General
They are all hydrocarbons with both Nitrogen and Carboxy properties.

Not only do they all share that. They are seemingly also the only ones that are possible?. The few hydrocarbons that cant be oxidized are seemingly the constituents of the cell.

Nitrogen that close to carboxy, an absolute no for degradation.
Some aa. more common than others. Why? Those are good hypothesis. Sequestering. A cell on its own can only be logically understood in itself. And possibly with self similar around.

Not in a greater setting.

# Branched-chain amino acid catabolism
Degradation of branched-chain **amino acids** involves the branched-chain alpha-keto acid dehydrogenase complex (BCKDH). A deficiency of this complex leads to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine).



# Non proteinogenic amino acids

[Make page on, non proteinogenic amino acids. Dont know much about these. Its interesting tho. Those would be the first in line to actually BE handled by an OXPHOS-centric cell. "Current oxy-life is what survived the big "fire". Those few things left over that didnt immediately (gradually, naturally) burn away as the atmosphere became oxygenated. Its not the origin of life, just like mammals are not the orgin of life. They "originiated" in when they became dominant. When the oppertunity arose. Not because they gradually became better. They did their thing. And that thing eventually became pivotal. That's the power of divertsity.])


# Non-ribosomal peptides synthetase

[See NRPs](https://hackmd.io/@sholmqvist/BJpKurTBB/%2Fkuws1ReMQvK9WrT-C9et5Q)

# Precursors for neurotransmitters
These neurotransmitters are synthesized in the brain from aromatic amino acid precursors that have to be obtained from the circulating blood.

factors which alter the rates of entry of four amino acids (the important neurotransmitter precursors L-tyrosine and L-tryptophan, as well as L-phenylalanine and L-histidine) into the brain

# Amines

An organic compound that contains an amino group is called an amine
Amines are derivatives of the inorganic compound ammonia, NH~3|
The breakdown of amino acids releases amines

Many neurotransmitters are amines, including epinephrine, norepinephrine, dopamine, serotonin, and histamine



# Deamination - Formation of ammonia

Example of Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process.

Spontaneous deamination of 5-methylcytosine results in thymine and ammonia. This is the most common single nucleotide mutation.

Broken down by
[aminotransferases // deaminases](https://sci-hub.se/https%3A//www.sciencedirect.com/science/article/pii/B9780123919090500098)

APOBEC1
APOBEC3A-H, APOBEC3G - affects HIV
Activation-induced cytidine deaminase (AICDA)
Cytidine deaminase (CDA)
dCMP deaminase (DCTD)
AMP deaminase (AMPD1)
Adenosine Deaminase acting on tRNA (ADAT)
Adenosine Deaminase acting on dsRNA (ADAR)
Adenosine Deaminase acting on mononucleotides (ADA) severe combined immunodeficiency disease (SCID) which is the result of a deficiency [if Adenosine can't be broken down -> Immune problem. Why? What does Adenosine do to immune cells? Inhibit?
Guanine Deaminase (GDA)

## Transaminase - Transfers
In transamination, the NH2 group on one molecule is exchanged with the =O group on the other molecule. The amino acid becomes a keto acid, and the keto acid becomes an amino acid

Valproic acid - a GABA transaminase inhibitor

---

**Alanine Transaminase**
Glutamic--Pyruvic Transaminase
**GPT gene**
Gpt Gpt2

It catalyzes the two parts of the alanine cycle

L-alanine + α-ketoglutarate ⇌ pyruvate + L-glutamate

**Serum ALT level, serum AST (aspartate transaminase) level, and their ratio (AST/ALT) (GPT/GOT)**

---

**GOT1 // glutamic oxaloacetic transaminase**
Aspartate transaminase // ALT
**GOT1 gene**

GOT1/cAST, the cytosolic isoenzyme derives mainly from red blood cells and heart.
GOT2/mAST, the mitochondrial isoenzyme is present predominantly in liver.

---

BCAT Branched aminoacid transaminase
Leucine

---

ABAT // **GABA Transaminase**
GABA -> SSA
[See succinic acid - lipids carboxy acids](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F5rJT0LufQUmVlokJJmw4Hg#Succinic-acid-C4)
[See lipids in cell types](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FUvNTWpCvR3W68aoFEHwRiQ#Succinate)
[See TCAastro slides](https://docs.google.com/presentation/d/1OBWe0RZk7GlKqi6yrUXaou-iYRY9BSwG5OhjTSUT1u0/edit#slide=id.g5ea4b824854a67c_0)
[See Adhfe1](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FGqPHdmsuSiSbRPZcVfM42w#ADHFE1)

OAT // Ornithine Aminotransferase


---

# Non-proteinogenic amino acids

[2020 Chem rev. Biosynthetic Pathways to Nonproteinogenic α-Amino Acids](https://pubs.acs.org/doi/10.1021/acs.chemrev.9b00408)

{%pdf https://sci-hub.se/downloads-ii/2019-12-24/ee/[e-mail]#view=FitH %}

# Aminoacids as Structured chemicals

## pKa of common aminoacids

A group’s pKa is the pH at which it is 50% protonated
A group is primarily protonated when the ambient pH is less than its pKa
We call the groups acidic (e.g. carboxylic acid) if they have a low pKa (i.e. they are deprotonated at neutral pH) and basic if they have high pKa.


A group’s pKa is the pH at which it is 50% protonated
A group is primarily protonated when the ambient pH is less than its pKa
We call the groups acidic (e.g. carboxylic acid) if they have a low pKa (i.e. they are deprotonated at neutral pH) and basic if they have high pKa.

Elements are most electronegative towards the upper right of the periodic table.
:heavy_minus_sign:

Peptide bonds are formed via a dehydration reaction. :ocean:

Peptide bonds have a resonance structure whereby about 40% of the time they are double bonds, which is why they stay fairly planar.

Cysteines can be oxidized to form disulfide bonds. The cytosol is reducing; disulfide bonds exist in oxidizing environments (e.g. extracellular)

C

## Chirallity, Isomers, L & D, optical active ...
L-amino acids represent all found in proteins from ribosome production
D-amino acids found in some proteins produced by **enzyme posttranslational modifications** and translocation to the endoplasmic reticulum, as in exotic sea-dwelling organisms such as cone snails.[36] They are also abundant components of the peptidoglycan cell walls of bacteria.

D-serine may act as a neurotransmitter in the brain.[10.1111/j.1742-4658.2008.06515.x](https://doi.org/10.1111%2Fj.1742-4658.2008.06515.x)

D-amino acids are used in [racemic crystallography](https://en.wikipedia.org/wiki/Racemic_crystallography "Racemic crystallography") 10.1002/pro.125 to create centrosymmetric crystals, which (depending on the protein) may allow for easier and more robust protein structure determination. [# What does this property of increased stability in a specific "D-/L- racemmix"-environment suggesting? Worth looking at which protein groups share such property?]

* They are not optically active. The L and D convention for amino acid configuration refers not to the optical activity of the amino acid itself but rather to the optical activity of the isomer of glyceraldehyde from which that amino acid can, in theory, be synthesized (D-glyceraldehyde is dextrorotatory; L-glyceraldehyde is levorotatory)

* In alternative fashion, the (S) and (R) designators are used to indicate the absolute configuration. Almost all of the amino acids in proteins are (S) at the α carbon, with cysteine being (R = because of nomenclature! not structure.) and glycine non-chiral

### D-Serine

serine racemase SRR
Alpha-Methylacyl-CoA Racemase Amacr

## Rotation angles of aminoacids



## VSEPR THEORY bond angle from electron distribution.

Aspartate (Aspartic acid)
Glutamate (Glutamic acid)

Glast - glutamate aspartate sympor (in cell membrane)
Glutamate aspartate antiporter (in mitochondrial membrane)

## Dibasic - lysine, arginine, ornithine - contains second basic group usually amino.

![Lysine](https://i.imgur.com/wRmQeGx.png "Lysine" =150x) ![Arginine](https://i.imgur.com/S7qOTzZ.png "Arginine" =150x) ![](https://i.imgur.com/WM7mC55.png "Ornithine" =150x)

---
# Amin Acids A-Ö
## Alanine
Hydrophobic
[See lacate](https://hackmd.io/@sholmqvist/BJpKurTBB/https%3A%2F%2Fhackmd.io%2FpppAihCtQOCwPq5J1Fu0VQ#Relation-to-Cori-cycle-and-Cahill-cycle) Alanin can be converted into pyruvate by deamination

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

Inter-conversion of alanine and pyruvate by AlaDH is central to metabolism in microorganisms. Its oxidative deamination reaction produces pyruvate This is done by ALT//GPT (astrocytes) and GOT2 (neurons, others)

L-alanine accounting for 7.8% of the primary structure in a sample of 1,150 proteins (second only to leucine)

Alanine is also very over-represented in low complexity regions of proteins

Collagen

The lactate shuttle is basically suggesting the Cori cycle in the relationship of neurons/astrocytes as muscle/liver
![Cori cycle](https://i.imgur.com/BMUWpaT.png "Cori cycle" =300x)

**Cahill cycle**
![](https://i.imgur.com/tZb7L1j.png "Cahill cycle" =300x)

---

[Also See Transaminase](#Transaminase)

---

Alanine is produced by reductive amination of pyruvate, a two-step process.

1. α-ketoglutarate, ammonia and NADH --> glutamate dehydrogenase // GLDH // Glud1 --> glutamate, NAD+ and water.

2. the amino group of the newly-formed glutamate is transferred to pyruvate by an aminotransferase enzyme, regenerating the α-ketoglutarate, and converting the pyruvate to alanine
GPT // GPT2 (astro)

Summary: pyruvate + ammonia --> alanine
(coupled to a-ketoglutarate --> glutamate)

=Both Glud1 and Gpt2 high in astrocytes==

Gpt2 is also high in CA1

# Aspartate
[See NAA N-acetyl-Aspartate in aminoacids](https://hackmd.io/@sholmqvist/BJpKurTBB/https%3A%2F%2Fhackmd.io%2F5WeiKeHbTsCQkizzoVeGnw#NAA-HMDB0000812)

Can act as an excitatory neurotransmitter in some brain regions

Asrgl1 // "Asparaginase And Isoaspartyl Peptidase 1"
Asparagine catabolic process via L-aspartate

- specific to glia
- May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester.
- Has both L-asparaginase and beta-aspartyl peptidase activity.
- no activity toward glutamine

---



AspAT = GOT2


<br><br><br><br><br><br>

# Arginin


# L-cysteine
semiessential

Hair is 10% cysteine
Skin is 14% cysteine,

[See FA sheet for solubility](https://docs.google.com/spreadsheets/d/1m2mHV2WSeV8XSYT9GT5xUU0FTjzT41Dw8M_lFFnn8Wo/edit#gid=1728414127&range=B71:K79)

[Cysteine enhances activity and stability of immobilized papain](https://link.springer.com/article/10.1007/s00726-009-0302-3)

Transported by Slc7a11
toghter with Glutamate

<p style="text-align:left;">

<iframe style="width: 247px; height: 300px;" frameborder="0" src="https://embed.molview.org/v1/?mode=balls&cid=5862"></iframe>
<span style="float:right;">

<iframe style="width: 247px; height: 300px;" frameborder="0" src="https://embed.molview.org/v1/?mode=balls&cid=595"></iframe>

</span>
</p>

<p style="text-align:left;">
Cysteine
<span style="float:right;">
Cystine
</span>
</p>

### Biosynthesis of Cysteine
Synthesis of cysteine relies on astrocytic CBS and CTH. Most cells can catabolize cysteine.

**In animals,** Produced from Serine & Homocysteine (e.a.a Methionine via S-adenosylmethionine).

Cystathionine beta-synthase (**CBS**). Homocysteine and serine to form the asymmetrical thioether cystathionine.

The enzyme cystathionine gamma-lyase (**CTH**) converts cystathionine into cysteine and alpha-ketobutyrate.

alpha-ketobutyrate (*not alpha-Ketoglutaric acid*)
converted to propionyl-CoA by branched-chain alpha-keto acid dehydrogenase complex BCKDC (incl. DLD? )
[Also See propionic acid](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F5rJT0LufQUmVlokJJmw4Hg#C30-Propionic-acid-HMDB0000237)

|||
|-|-|
|**Anabolism**|| |
|Catabolism| |
(Propionyl CoA carboxylase PCCA,PCCB)
(Methylmalonyl-CoA Mutase MMUT)| Methylmalonyl CoA - Succinyl-CoA

In plants and bacteria, cysteine biosynthesis also starts from serine, which is converted to O-acetylserine by the enzyme serine transacetylase. The enzyme cysteine synthase, using sulfide sources, converts this ester into cysteine, releasing acetate.

### Homocysteine
[See SAM and MET cycles](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FHvBYED0fQeqORjIwdvNQqA)
non-proteinogenic

Methionine, SAM (methylation of histones), Glycine-Sarcosine


CBS does upper reaction.

CTH does lower reaction.

[See Slides TCA](https://docs.google.com/presentation/d/1OBWe0RZk7GlKqi6yrUXaou-iYRY9BSwG5OhjTSUT1u0/edit#slide=id.g12fd9a739a2_0_0)

cysteine aminotransferase
GOT1 is also CTA "cysteine aminotransferase"

This would suggest it can deaminase cysteine producing 3-mercaptopyruvate

SQR

See this article on the effect of NAC. They say NAC is such a good antioxidant because it states that NAC in itself is not a good oxidant and therefore the mechanism is unknown.
They suggest its broken to H2S that oxidize roGFP2.

[2018 N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production](https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(18)30033-3)

3-mercaptopyruvate sulfurtransferase

[[[For me it would be more obvious that NAC competitively compeet with Cysteine blocking its deamination by Got1/Cysteine aminotransferase. This interferes with its conversion to 3MP and aKG-Glu. I.e. it cant reduce the size of the TCA. 3MP may be highly oxidative in that it facilitates the oxidation in the TCA.]]]

### N-acetylcysteine (NAC)
N-acetylcysteine (NAC)

It is being studied in conditions, such as **autism**, where cysteine and related sulfur amino acids **may be depleted** due to multifactorial dysfunction of methylation pathways involved in methionine catabolism

### Mercapturic acid
Detoxification end product of glutathione

[See Glutathione](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FsZITyKgiSTGGEHEpKig2cw)

[See GSH](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FUDEo9fMDTPu0x9GGTDEGhg#GSH-hoards-all-the-cysteine%E2%80%94what-a-slimy-thing-to-do)

[See Mercapturic acid](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F5rJT0LufQUmVlokJJmw4Hg#Mercapturic-acid)

### Cysteine and evolution
[Relationship Between the Occurrence of Cysteine in Proteins and the Complexity of Organisms](https://academic.oup.com/mbe/article/17/8/1232/992796)

The occurrence and relative positions of cysteine residues were investigated in proteins of various species.

Considering random mathematical occurrence for an amino acid coded by two codons (3.28%), **cysteine is underrepresented in all organisms investigated**.

Representation of cysteine appears to **correlate positively with the complexity** of the organism, ranging between 2.26% in mammals and 0.5% in some members of the Archeabacteria order
[higher in more complex organisms]

Table 1 . Animals have more Cysteine in Ribosomal Proteins of Various Species.

### Methylcitrate cycle

[L-cysteine is a precursor to the biologic antioxidant glutathione](https://hackmd.io/@sholmqvist/BJpKurTBB/https%3A%2F%2Fhackmd.io%2FSfqcAU4uTK-tBuX41qqFrg#Glutathione)

### Slc7a11 - In astro. Glutamate-Cysteine antiporter.
sodium-independent, anionic amino acid transport system that is highly specific for cysteine and glutamate. In this system, designated Xc(-), the anionic form of cysteine is transported in exchange for glutamate.

> We report that the cystine/glutamate transporter xCT is essential for RAS-induced tumorigenicity by enhancing antioxidant glutathione synthesis. Our findings uncover that RAS controls xCT transcription by downstream activation of ETS-1 to synergize with ATF4 https://www.pnas.org/content/116/19/9433

### Selenocysteine

[Also see Ions Selenite](https://hackmd.io/@sholmqvist/BJpKurTBB/https%3A%2F%2Fhackmd.io%2FmkCWgpLJQWWBSjCGd1yDtA#Selenite)

Found in DIO2

Selenocysteine is located in the active sites of enzymes that participate in oxidation–reduction reactions.

Its antioxidant activity arises from its ability to deplete reactive species. Selenium and sulfur are chalcogen elements that share many chemical properties and the substitution of methionine to selenomethionine may have no effect on protein structure and function. However, the incorporation of selenomethionine into tissue proteins and keratin in horses causes alkali disease. Alkali disease is characterized by emaciation, loss of hair, deformation and shedding of hooves, loss of vitality, and erosion of the joints of long bones.

(Cystein but with Selenium instead of sulphur.)
biochemist Thressa Stadtman

Selenocysteine exists naturally in all three domains of life, but not in every lineage, as a building block of selenoproteins

Present in several enzymes (for example glutathione peroxidases, tetraiodothyronine 5′ deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases, selenophosphate synthetase 2, methionine-R-sulfoxide reductase B1 (SEPX1 // MSRB1), and some hydrogenases)

Selenocysteine has both a lower pKa (5.47) and a lower reduction potential than cysteine. Properties make suitable in proteins that are involved in **antioxidant activity.**

### Cystine_knot
https://en.wikipedia.org/wiki/Cystine_knot

NDP Norris disease protein
- wnt signaling

NGF Nerv growth factor

### Cysteinyl_leukotrienes

# Leucine
Branched aminoacid

[See mTOR signaling](https://hackmd.io/@sholmqvist/BJpKurTBB/https%3A%2F%2Fhackmd.io%2FHi_KrVDMS72extkwqJfUJw#mTORC-and-Leucine)

[How the amino acid leucine activates the key cell-growth regulator mTOR](https://www.nature.com/articles/d41586-021-01943-7)

# Iso-Leucine
Branched aminoacid

# Proline
[See Collagen](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FRW2q-ZQ1TLqiDgRAvsRyRA)

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


[20230923 Now I am interested in how Proline and glycine seems to be what neuron torde to want to get rid of. ]

==[Here I am intersted in how proline and collagen relates to the TCA through Glutamate.]==
[Possibly neurons form Proline as a by product. This is then degraded in Astrocytes by Prodh]

[This is supported by neurons express Ald18a1 or Pcyr1 "forming Proline from glutamate"]

[See Astrocyte genes Prodh](https://hackmd.io/@sholmqvist/BJN5dmhLu/%2F038vIB9uTSGAKcrStOuOHg#Prodh)
[See ECM](https://hackmd.io/@sholmqvist/BJpKurTBB/%2Fc7UkEUBYT26RS-oIC2bVZA#ECM-and-nutrient-stress)

Pipecolic acid is same but C6 instead of C5
[See Pipecolic acid ](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F5rJT0LufQUmVlokJJmw4Hg#Pipecolic-acid)
[See TCA slides Lysine, Glutamate, AAS alpha aminoadipic semialdehyde](https://docs.google.com/presentation/d/1OBWe0RZk7GlKqi6yrUXaou-iYRY9BSwG5OhjTSUT1u0/edit#slide=id.g15c540cb5a4_0_1)

---

Proline can be synthesized from glutamine as well as derived from collagen degradation. The metabolism of proline serves as a source of energy during stress, provides signaling reactive oxygen species for epigenetic reprogramming and regulates redox homeostasis

---


**"Glutamate snake biting its own nitrogen"**
[Which happens when O is low i.e in neurons]

---

[ ](https://link.springer.com/article/10.1007/s00726-021-02981-1)
[Proline metabolism and transport in retinal health and disease](https://link.springer.com/article/10.1007/s00726-021-02981-1)


Proline is catabolized into P5C [In astro], a key intermediate which serves as a precursor for glutamate, glutamine and ornithine.

The otherway, Pycr1 (Pycr2, Pycr3 (cytosolic)
Aldh18a1 - Glutamate -> P5C
(jmf P5CDH // Ald4a1)

[Aldh18a1 is the Aldh that is highest in Neurons (sharmar) this is odd since these cells supposedly wants to make Glu for glutamatergic signaling. ~~ unless they actually are trying to get rid of Glutamate.]
[-> this line of reasoning means that For some reason GABA ergic has settled for getting rid of GABA instead. Perhaps this is more efficient in ]

Pycr1 - P5C -> Proline

**This is marker for comitted OPC**s
See linnarsson.
Why would oligos who just became comitted to produce proline?

[Beacuse this inhibitd their TCA?]
[Neurons do not want proline for the same reason. They prefer Glutamate, as they have GOT2?]


==["the use of glutamate for fuel, is coupled to production of alanine (GPT/Alt in astrocytes) and aspartate (Got2 in neurons)"]["Astrocytes are needed to breakdown Collagen/proline into glutamate"]==

GPT = Alt // alanine transaminase
GOT2 enable glutamate to be used for fuel. Astrocytes are low in this, while other cell types are high, particularily neurons.
These to reactions are bidirectional.

[Astrocytes that do b-oxidation constantly expand its TCA metabolite pool.]

Aldh4a1 = P5CDH
See Aldh4a1

**Prodh**: mitochondrial protein that catalyzes the first step in proline degradation
Introduces a doublebond into the proline cyclic.
(forming P5C which converts to Ornithin **or** glutamate)

mitochondrial inner membrane flavoprotein

**plod1 plod2 prep p3h1 p3h2 fkbp3**

**Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase**
Plod1
plod2
hydroxylation of lysyl (lysine) residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks

## Hydroxyproline
Prolyl Hydroxylase
The enzyme catalyzed reaction takes place in the lumen of the endoplasmic reticulum.

L-proline + alpha-ketoglutaric acid + O2 → (2S, 4R)-4-hydroxyproline + succinate + CO2

**Prolyl 3-Hydroxylase**
Introduces a hydroxygroup in proline
P3H1
P3H2
P3H3
P3H4 (Inactive)

**Prolyl 4-Hydroxylase**
"major component of the protein collagen"
P4HA1
P4HA2
P4HA3
P4HB
P4HTM (up in cold proteomics Astro Holmqvist)
https://docs.google.com/spreadsheets/d/1Kb0LWjObdllfbeG9qnsMhUJIhdFW-RHdc6ExS7CzD70/edit#gid=1148296073&range=A1891


## Proline transporters

Slc6a7

Sit1 // Slc6a20 // Sit1
https://link.springer.com/article/10.1007/s00726-021-02981-1

Retinal epithelial cells prefer eating lipids and proline. Suggesting these are produced.

"Remarkably, the neural retina rarely imports proline directly, but it uptakes and utilizes intermediates and amino acids derived from proline catabolism in the RPE."
[Beacuse they try to get rid of specifically proline, that is formed when there is glutamate but no oxygen.]

### Crym
Proline can be formed from Ornithine in bacteria
[May be functional in astrocytes, that express this? See [Sharma](https://docs.google.com/spreadsheets/d/1w32HIRZfz-5ZrBswyEgS9Se63jPfDCsdZKbP7Gh8JlY/edit#gid=0&range=A2788)]
The (not functional in retina) enzyme Crym is similar to the bacterial enzyme.

Crym
binds thyroid hormone for possible regulatory or developmental roles.

Associated with deafness

<br><br><br><br>




https://en.wikipedia.org/wiki/Hydroxyproline

### Proline Glutamine and collagen
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228914/
"Recent data provided evidence that __extracellular Pro__ (added to culture medium) had significant, but relatively __little impact__ on collagen biosynthesis in fibroblasts (the main collagen synthesized cells) cultured **in the presence of glutamine** (Gln).
However, extracellular Pro drastically increased collagen biosynthesis in the cells cultured in Gln-free medium. It suggests that Pro availability determines the rate of collagen biosynthesis and demand for Pro in fibroblasts is predominantly met by conversion from Gln."

[20230923 Collagen is produced by skin cells, as they are exposed to oxygen, they use enthalpy to form proline and the this enthalpy is shed off.][Like the flagella shedding its tail]

[Interpret. Proline is a byproduct in neuronal metabolism. When Glutamine is present, the neurons can still run. But without Gln, then Proline needs to be sequestered to balance the anapletoric mechanisms.]

Glutamate ruins the oxidation of short chain dicarboxy acids in neurons. but why. and why in neurons. This must be related to why they do in the end secret glutamate (which is very close to being anapletoric)

Is Aldh18a1 & Pycr1 in neurons, then this fits nicely.

Aldh18a1 - Pyrroline-5-Carboxylate Synthetase (Glutamate Gamma-Semialdehyde Synthetase)

Pycr1 - Pyrroline-5-Carboxylate Reductase 1

### Additional on proline

Additionally, proline is the only amino acid that does not form a blue/purple colour when developed by spraying with ninhydrin for uses in chromatography. __Proline, instead, produces an orange/yellow colour__.

__osmoprotectant__

__In plants__, proline accumulation is a common physiological response to various stresses but is also part of the developmental program in generative tissues (e.g. pollen)

Proline is __biosynthetically derived from__ the amino acid L-glutamate. Glutamate-5-semialdehyde is first formed by glutamate 5-kinase (ATP-dependent) and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). This can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase (using NADH or NADPH), or turned into __ornithine__ by ornithine aminotransferase, followed by cyclisation by ornithine cyclodeaminase to form proline.

Glutamate - Ornithinin - Proline

The distinctive __cyclic structure__ of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids

Proline acts as a __structural disruptor__ in the middle of regular secondary structure elements such as alpha helices and beta sheets; however, proline is commonly found as the first residue of an alpha helix and also in the edge strands of beta sheets.

Proline is one of the two amino acids that do __not follow__ along with the typical __Ramachandran plot__, along with glycine


---


# Serine

* **Serine restriction alters sphingolipid diversity to constrain tumour growth**
* https://sci-hub.se/10.1038/s41586-020-2609-x
* Serine, glycine and other nonessential amino acids are critical for tumour progression. However, the molecular mechanisms driving this response remain unclear and the efects on lipid metabolism are relatively unexplored. Serine palmitoyltransferase (SPT) catalyses the de novo biosynthesis of sphingolipids but also produces **noncanonical 1-deoxysphingolipids** when using alanine as a substrate.
* Deoxysphingolipids accumulate in the context of mutations in SPTLC1 or SPTLC26,7 —or in conditions of low serine availability —to drive neuropathy, and deoxysphinganine has previously been investigated as an anti-cancer agent

Formation of sphingolipids
Serine palmitoyltransferase (SPT) (PubMed:19416851). The heterodimer formed with SPTLC2 or SPTLC3 constitutes the catalytic core (PubMed:19416851). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851). Required for adipocyte cell viability and metabolic homeostasis

Restriction of dietary serine and glycine potently induces the accumulation of deoxysphingolipids while decreasing tumour growth in xenograft models in mice. Pharmacological **inhibition of SPT rescues** xenograft growth in mice fed diets restricted in serine and glycine, and the reduction of circulating **serine by inhibition of phosphoglycerate dehydrogenase (PHGDH)** leads to the accumulation of deoxysphingolipids and mitigates tumour growth. The promiscuity of SPT therefore links serine and mitochondrial alanine metabolism to membrane lipid diversity, which further sensitizes tumours to metabolic stress.

## PHGDH in relation to mitochondria.
This needs to be read and rewritten.
[I think the main point here is that PHGDH mediates two separate conversions of metabolites close to the TCA]
C3 alpha=O generates serine, cysteine, glycine.

and

C5 alpha=O generates an inhibitor of cellular hydroxylations.

This occur when oxygen is low.
Formation of proteins.
Reducing the amount of oxygen used elsewhere.

Protein formation is a sequestration of NH+ which makes the TCA run smoother.

[If mito run too hot, it will eat also proteins, which then release NH+]

NH interfere with CO2/HCO3 formation generating simple Carbamides (Urea).

a feedback inhibiting the activity of the mitochondria. lowering its temperature.

## Two reactions occur.
==(consider removing all below - wrote as I reasoned. COntains contradictions.)==

*2-hydroxyglutarate + NAD+ ⇌ 2-oxoglutarate + NADH + H+*
High energy, when balancec is to the right.

The conversion of AKG to an inhibitor of those proteins that depend on it for their activity. Alpha-ketoglutarate-dependent hydroxylases.

In high energy state an excess of TCA metabolites activates hydroxylation of proteins via AKG.
(high energy state, desaturations, oxylipins, demethylations, and carnitine/FA use).
Excess TCA metabolite opens chromatin.

Decreased oxygen low TCA metabolite leads to closure of chromatin, reduced FA import. . .

High energy state also result in excess formation of 3-phosphonooxypyruvate and subsequent Serine/aa.

Low energy state here converts proteins into G3P as for use in TCA as fuel.

Decreased oxygen lead to formation of
*3-phospho-D-glycerate + NAD+ ⇌ 3-phosphonooxypyruvate + NADH + H+*

2-hydroxyglutarate and NAD+ <-> 2-oxoglutarate, NADH, and H+.

PHGDH converts alpha-ketoglutarate by reducing it to 2-Hydroxyglutaric acid. This moves this piece of mass from being structural components direct intermediate of the TCA, to instead being more accessible as fuel.

This is coupled to its main described function
Reducing phospho-glycerate's hydroxy group into the keton group of phospho-Phosphohydroxypyruvic acid.

This is the "committed step" of serine- and in extension Cysteine and glycine.

As such, holistical view becomes:
when short (5,3 carbon) oxidized acyls leave the mitochondria they loose their hydrogens become oxidized into more reactive compounds (sticky) (so that the oxygen groups hinders their conversion to fuel) these then are substrates in glycolysis, and substrates for certain aa.

NAD+ is the oxidized form - it lacks electrons.
This makes sense as there is 700:1 ratio of NAD+ : NADH.
This is not a reflection of lack of H+ it is due to the excess of O (that steals all H).

NAD+ levels are highest in the mitochondria. This reflects that this is where the vacuum of oxygen happens, where "available" oxygens are bind to Carbon forming CO2. This CO2 is so tightly bound that it in effect captures the oxygen "permanently". CO2 excists is partly dissolved in H20 as HCO3.
The tight bond makes it energetically expensive to convert to fuel.
So much so that it is extruded from the mitochondria, cell, tissue, and organism.

one can see the function of PHGDH as a node that handles those compounds closest but not possible to use for fuel.

G3P beacuse it is too short. And 2oxoglutarate as it is too long (C5). Their shared group of oxygenated alpha-carbon.

C5 is an acutal intermediate of the TCA.
C3 is a breakdown product of glucose. I.e. it needs more oxygen to become available as fuel.

This means that when oxygen is low, half burned glucose forms a precursor for serine and cysteine. As it leaves the mitochondria, a hydrogen is stolen by NAD+ (which makes it sticky (wants to donate electrons). Which can be assumed by a nitrogen.
[I predict there is a keton specificty of aminetransferase that generates serine.]

In hypoxia, the cell produces serine/cysteine/ from glucose.
Note this is not a desire, but an entropically driven reaction due to low activity in the mitochondria.

Concurrently the excess of TCA intermediate AKG, is in a similar process for same reasons converted into

3-phospho-D-glycerate + NAD+ ⇌ 3-phosphonooxypyruvate + NADH + H+
As C3 alpha=O leaves mitochondria they are

2-hydroxyglutarate + NAD+ ⇌ 2-oxoglutarate + NADH + H+

As c5 alpha=O leaves mitochondria, into the relatively oxygen poor cytosol, it acts as a competitive inhibitor for AKG-dependent enzymes.
- This arguably is how an overscaled TCA translates into lowered cellular activity (of AKG-dependent oxygenases?)

---

# Homoserine
Non-protogenic.

![](https://i.imgur.com/qFgOID5.png "homoserine" =200x)![](https://i.imgur.com/Fd052h6.png "serine" =100x)

lactone form "biting its own tail."

Homoserine is converted to o-succinyl homoserine by homoserine o-succinyl transferase, a precursor to L-methionine.

![](https://i.imgur.com/eBnJ5dq.png "precursor of methionine"=200x)
==There must be something here with the initiation of peptides?==

### Homoserine Synthesis
**Biosynthesis pathway for homoserine.**

# Glycine

[See Serine & Glycine in sphinoglipid diversity](https://hackmd.io/@sholmqvist/BJpKurTBB/%2F6boDt7fZRfmxzsr9k2HIgg#Serine)

[See Collagen](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FRW2q-ZQ1TLqiDgRAvsRyRA)

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


simplest amino acid
inhibitory neurotransmitter

Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form.

abundant amino acid in collagen triple-helices

When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP)

--

[See Gl/Gln AMPAr] (https://hackmd.io/@sholmqvist/BJpKurTBB/%2FOycr1qjqTeiFmC2iQLAVH)

Glycine Potentiates AMPA Receptor Function through Metabotropic Activation of GluN2A-Containing NMDA Receptors. NMDA receptors are Ca2+-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function.29 Sept 201
Grin2d

# Methionine

[See SAM and THF cycles](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FHvBYED0fQeqORjIwdvNQqA#SAM-and-THF)

==An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand==

Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids. Excluding the few exceptions where methionine may act as a redox sensor (e.g.,[10])

Cysteine 


[Shouldnt there be some biochemical logic to why in particular Methionine is always first in proteins and why the codon AUG "codes" for it. If its a code, what is the information behind the first letter? and also the only thioester aa]

==protein are the ash of hydrocarbon combustion, another type of ash is the methylgroups. that need to form ==

Methyl: It can act as either a strong oxidant or a strong reductant, and is quite corrosive to metals. https://en.wikipedia.org/wiki/Methyl_radical

[Seemingly, and from the looks of it, it is very difficult to "burn the fire of the cell"
as such methionine circles around driving
1. Methylation.
2. Protein formation and Cysteine (not Cystine aa)
Add Serine, Add Glutamte, Add Glycine = Gluthatione, "the main antioxidant"
3. With THF, Met drives purine and pyrimidine synthesis? DNA = Aromatic Nitrogen Carbons]
4.

[Sulphur and 02 forms acid if burn energy added, dissolving as H2SO4 in water.]


Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids
https://www.nature.com/articles/s41467-023-38289-9

**Methionine in proteins: The Cinderella of the proteinogenic amino acids** 2019 Review. Juan C. Aledo
https://onlinelibrary.wiley.com/doi/full/10.1002/pro.3698

**Methionine: A metabolically unique amino acid** - 2007. Livestock Science (!!!)
https://www.sciencedirect.com/science/article/pii/S1871141307004192

**Methionine in Proteins: It’s not just for protein initiation anymore** - 2019. Neurochem Res.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446232/

The start codon always codes for methionine in eukaryotes and Archaea and a modified Met (fMet) in bacteria, mitochondria and plastids

N-terminal of peptides

Can be removed by post-translational modification

> #Met is limiting in initiation of Protein synthesis (only indirectly (?) in mitochondria) by being the start codon AUG-aminoacid.

> Protein synthesis (initiator)
Glutathione
Homocysteine
Methylation
Energy production by fMet.
inflammation - regocnition of fMet as bacterial proteins by Fpr1 (expressed on microglia)

### Activation
As with phosphorylation, enzymatically-mediated oxidation and reduction of specific methionine residues functions as a regulatory process in the cell.

### Stability
Methionine residues also form bonds with aromatic residues that contribute significantly to protein stability

### Oxidized methionine
methionine sulfoxide
methionine sulfone

**methionine sulfoxide reductase**
MSRA
MSRB1
MSRB2
MSRB3

### Biosynthesis

---

### N-Formylmethionine - fMet
in bacteria and mitochondria
Addition of the formyl group to methionine is catalyzed by the enzyme methionyl-tRNA formyltransferase. This modification is done after methionine has been loaded onto tRNAfMet by aminoacyl-tRNA synthetase.

__Methionyl-tRNA formyltransferase__
__MTFMT__ - Mitochondrial Methionyl-TRNA Formyltransferase
This enzyme participates in 3 metabolic pathways:
- methionine metabolism,
- one carbon pool by folate
Folate, distinct forms of which are known as folic acid, folacin, and vitamin B9
tags: homocysteine depression
###### tags: `homocysteine` `depression`
- aminoacyl-tRNA biosynthesis - transcription
amino acid + ATP + tRNA ↔ aminoacyl-tRNA + AMP + PPi

---

# Glutamate

[See also GluGln Receptors](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FOycr1qjqTeiFmC2iQLAVHA)

**GLUD1 GLUD2** (Mm Glud1) converts glutamate to α-ketoglutarate, and vice versa
That is couples TCA to cellular glutamate levels/signaling. (Red. anm).

alpha-ketoglutarate produced by deamination of glutamate

alanine transaminase (ALAT//ALT//**GPT**) converts α-ketoglutarate and L-alanine to L-glutamate and pyruvate, respectively, as a reversible process

---

# Histidine
Histidine in Proteins: pH-Dependent Interplay between π–π, Cation–π, and CH–π Interactions

# Threonine


2005 Edgar - Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene
The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC555945/

* Three L-threonine (L-alpha-amino-beta-hydroxybutyric acid) degradation pathways

- L-threonine aldolase (**L-TA**)(EC 4.1.2.5)(gene **GLY1**)
- L-serine/threonine dehydratase (**SDH**)(EC 4.2.1.16)(gene **SDS**)
- L-threonine 3-dehydrogenase (EC 1.1.1.103)(**TDH**)

### Gly1 Tha1 // THA1P (Pseudogene)
Threonine - to - glycine and acetaldehyd

The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR.

### TDH (Pseudogene)
L-Threonine Dehydrogenase (Pseudogene)

### SDS (EC 4.2.1.19/17) In astrocytes
L-serine - to - pyruvate and ammonia

https://www.brenda-enzymes.org/enzyme.php?ecno=4.3.1.17

Threonine - to - NH4+ and 2-ketobutyrate
https://www.brenda-enzymes.org/enzyme.php?ecno=4.3.1.19

### SDSL
same EC# as SDS

Has low serine dehydratase and threonine dehydratase activity.

Diseases associated with SDSL include Subdural Empyema and Brain Compression. Among its related pathways are threonine degradation and Sulfur amino acid metabolism

mathematical ability rs12814443
body mass index rs729062

### KYNU // Kynureninase (alternative to SHTM1/2 and Gly1//THA1P)
EC 3.7.1.3


  

  

  

---

# Tyrosine TYR
non-essential amino acid
Mammals synthesize tyrosine from the essential amino acid phenylalanine (phe)

Tyrosine

NE
Tyramine - unable to cross the blood-brain barrier - Foods that are fermented
Octopamine - invertebrate correlate to NE.

In lobsters, octopamine seems to direct and coordinate neurohormones to some extent in the central nervous syste

Octopaminergic nerves in the mollusc may be present in the heart, with high concentrations in the nervous system

Octopamine might be an important amine that influences the therapeutic effects of inhibitors such as monoamine oxidase inhibitors

MAOs breakdown monoamine neurotransmitters. Thus inhibition of MAOs might lead to increased levels of octopamine in treatment of depression.

---

# Tryptophan
[Also see Serotonin](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FGM9BEBVTQLmcV6ha-pQO8w)

Can be converted to Serotonin (and subsequent Melatonin)

Precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3

### Degradation of Tryptophan
**First step**
Degradation starts with IDO1,2 or TDO2. See below.
Produce L-Kynurenine (HMDB0000684)
Is this released?

used in the production of niacin Vitamin B3

**Second step**
Degradation of Tryptophan in Microglia gives inflammation.

Degradation of Tryptophan in Astrocytes gives Kynurenic acid.
Kynurenic acid (KYNA or KYN)
> possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors. Wiki

> High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis,[8] schizophrenia and HIV-related illnesses

> When researchers decreased the levels of kynurenic acid in the brains of mice, their cognition was shown to improve markedly. http://10.1038/npp.2010.39.

> neuroprotective properties https://doi.org/10.1007%2F978-1-4614-5836-4_92

> One controlled study kept mice on a ketogenic diet and measured kynurenic acid concentrations in different parts of the brain. It found that the mice on the ketogenic diet had greater kynurenic acid concentrations in the striatum and hippocampus compared to mice on a normal diet, with no significant difference in the cortex.https://doi.org/10.1007%2Fs00702-011-0750-2

> Kainic acid is an agonist for Kainate excitatoryx receptors. Kynueric acid is an antagonist.

BBOX is incresed in epilepsy mouse model using kainic acid to enhance excitatory signaling. (==> astrocytic kynuceric acid production lantagonise excitation. (protein/Tryptophan catabolism correlated with lower BBOX?))

**In Microglia**
"Kynurenine 3-Hydroxylase / Kynurenine 3-Monooxygenase"

KMO is expressed which enables further breakdown to toxic metabolites picolinic acid (inflammation) and Quinolinic acid.

**In astrocytes**
Express Kynuramine amino transferases I, II, III,
Does not express KMO

https://www.sci-hub.se/10.1093/schbul/sbm030

### KYNA synthesis
- Synthesis is initiated by the oxidative ring opening of tryptophan by indoleamine 2,3-dioxygenase (IDO1,2) and/or tryptophan dioxygenase (TDO2).

TDO2 SchrimerHs Layer 4 cortical projection neurons and VIP interneurons.

L-Kynurenine (HMDB0000684)

- The reaction product of IDO and TDO, kynurenine, is then irreversibly converted to KYNA

- KYAT Kynurenine—oxoglutarate transaminase then irreversibly convert kynurenine into 4-(2-aminophenyl)-2,4-dioxobutanoate.

L-kynurenine + 2-oxoglutarate :arrow_backward::arrow_forward: 4-(2-aminophenyl)-2,4-dioxobutanoate + L-glutamate

KYAT1 (Mm Ccbl1)
AADAT (aka KYAT2) In astro
KYAT3 (Mm Ccbl2) In astro
GOT2 (aka KYAT4)

4-(2-aminophenyl)-2,4-dioxobutanoate is unstable and collapse into Kynurenic acid (HMDB0000715)

increased in schizophrenia and other disease brains.

**Enzymes**


ITO1,2 Indoleamine dioxygenase

TDO2 Tryptophan dioxygenase

- KMO kynurenine-3-monooxygenase // Kynurenine 3-Hydroxylase

KYNU Kynureninase (L-Kynurenine Hydrolase)

HAAO 3-hydroxyanthranilate oxidase // 3-Hydroxyanthranilate 3,4-Dioxygenase

**Metabolites**

2-Amino-3-carboxymuconic acid semialdehyde (**HMDB0001330**)
"ACS"

very strong basic compound

Picolinic acid (HMDB0002243)

Picolinic acid is a metabolite of the tryptophan catabolism. Picolinic acid is produced under inflammatory conditions and a costimulus with interferon-gamma (IFNgamma) of macrophage (Mphi) effector functions

Quinolinic acid (HMDB0000232
(Forms non-enzymatically from **HMDB0001330**)

Quinolinic acid is a very strong basic compound (based on its pKa)
Quinolinic acid is a metabolite of tryptophan with a possible role in neurodegenerative disorders.

# Valine

Branched aminoacid

---