Homocysteine

Source: Wikipedia, the free encyclopedia.
Not to be confused with homocystine.
Homocysteine
Skeletal formula
Ball-and-stick model
Names
IUPAC name
2-Amino-4-sulfanylbutanoic acid
Identifiers
(L-isomer) checkY
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.006.567 Edit this at Wikidata
EC Number
  • 207-222-9
KEGG
UNII
 (L-isomer) checkY
  • InChI=1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7) checkY
    Key: FFFHZYDWPBMWHY-UHFFFAOYSA-N checkY
  • InChI=1/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)
    Key: FFFHZYDWPBMWHY-UHFFFAOYAS
  • C(CS)C(C(=O)O)N
Properties
C4H9NO2S
Molar mass 135.18 g/mol
Appearance White crystalline powder
Melting point 234–235 °C (453–455 °F; 507–508 K)[2] (decomposes)
soluble
log P -2.56 [1]
Acidity (pKa) 2.25 [1]
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H302
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Homocysteine (

α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In the body, homocysteine can be recycled into methionine or converted into cysteine with the aid of vitamin B6, B9, and B12.[3]

High levels of homocysteine in the blood (

coronary arteries, which supply the heart with oxygenated blood.[4][5]

Hyperhomocysteinemia has been correlated with the occurrence of blood clots, heart attacks, and strokes, although it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions.

neural tube defects.[8]

Structure

Zwitterionic form of (S)-homocysteine (left) and (R)-homocysteine (right)

Homocysteine exists at neutral pH values as a zwitterion.

Biosynthesis and biochemical roles

Two of homocysteine's main biochemical roles - (Homocysteine is seen in the left middle of the image.) It can be synthesized from methionine and then converted back to methionine via the SAM cycle or used to create cysteine and alpha-ketobutyrate.

Homocysteine is biosynthesized naturally via a multi-step process.

tetrahydrofolate (THF) back into L-methionine or conversion to L-cysteine.[10]

Biosynthesis of cysteine

Mammals biosynthesize the amino acid cysteine via homocysteine.

Cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This reaction uses pyridoxine (vitamin B6) as a cofactor. Cystathionine γ-lyase then converts this double amino acid to cysteine, ammonia, and α-ketobutyrate. Bacteria and plants rely on a different pathway to produce cysteine, relying on O-acetylserine.[11]

THF
: tetrahydrofolate

Methionine salvage

Homocysteine can be recycled into

cobalamin (vitamin B12)-related enzymes. More detail on these enzymes can be found in the article for methionine synthase
.

Other reactions of biochemical significance

Homocysteine can cyclize to give

heterocycle. Because of this "self-looping" reaction, homocysteine-containing peptides tend to cleave themselves by reactions generating oxidative stress.[12]

Homocysteine also acts as an allosteric antagonist at Dopamine D2 receptors.[13]

It has been proposed that both homocysteine and its thiolactone may have played a significant role in the appearance of life on the early Earth.[14]

Homocysteine levels

Total plasma homocysteine

Homocysteine levels typically are higher in men than women, and increase with age.[15][16]

Common levels in Western populations are 10 to 12 μmol/L, and levels of 20 μmol/L are found in populations with low B-vitamin intakes or in the elderly (e.g., Rotterdam, Framingham).[17][18]

It is decreased with methyl folate trapping, where it is accompanied by decreased methylmalonic acid, increased folate, and a decrease in formiminoglutamic acid.[19] This is the opposite of MTHFR C677T mutations, which result in an increase in homocysteine.[citation needed]

Blood reference ranges for homocysteine:
Sex Age Lower limit Upper limit Unit Elevated
Therapeutic target
Female 12–19 years 3.3[20] 7.2[20] μmol/L > 10.4 μmol/L
or
> 140 μg/dl		 < 6.3 μmol/L[21]
or
< 85 μg/dL[21]
45[22] 100[22] μg/dL
>60 years 4.9[20] 11.6[20] μmol/L
66[22] 160[22] μg/dL
Male 12–19 years 4.3[20] 9.9[20] μmol/L > 11.4 μmol/L
or
> 150 μg/dL
60[22] 130[22] μg/dL
>60 years 5.9[20] 15.3[20] μmol/L
80[22] 210[22] μg/dL

The ranges above are provided as examples only; test results always should be interpreted using the range provided by the laboratory that produced the result.

Elevated homocysteine

Main article: Hyperhomocysteinemia

Abnormally high levels of homocysteine in the serum, above 15 μmol/L, are a medical condition called hyperhomocysteinemia.[23] This has been claimed to be a significant risk factor for the development of a wide range of diseases, including thrombosis,[24] neuropsychiatric illness,[25][26][27][28] and fractures.[29][30] It also is found to be associated with microalbuminuria, which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction.[31] Vitamin B12 deficiency, when coupled with high serum folate levels, has been found to increase overall homocysteine concentrations as well.[32]

Typically, hyperhomocysteinemia is managed with vitamin B6, vitamin B9, and vitamin B12 supplementation.[33] However, supplementation with these vitamins does not appear to improve cardiovascular disease outcomes.[34]

References

  1. ^
    PMID 19275147
    .
  2. doi:10.1021/ja01135a502
    .
  3. ^ "Homocysteine" (PDF). moh.gov.vn. Retrieved 5 April 2023.
  4. S2CID 3986295.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  5. ^ Boudi, Brian F. "Noncoronary Atherosclerosis". Medscape. Archived from the original on 2013-05-11.
  6. ^ Homocysteine: The Facts, Tufts Health and Nutrition Letter, July 31, 2020 update
  7. S2CID 26125655
    .
  8. ^ van der Put NJ et al Folate, Homocysteine and Neural Tube Defects: An Overview Archived 2015-09-16 at the Wayback Machine Exp Biol Med (Maywood) April 2001 vol. 226 no. 4 243-270
  9. S2CID 2335090
    .
  10. ^ Champe, PC and Harvey, RA. "Biochemistry. Lippincott's Illustrated Reviews" 4th ed. Lippincott Williams and Wilkins, 2008
  11. ISBN 1-57259-153-6
    .
  12. PMID 20080717
    .
  13. PMID 17081059. Archived
    (PDF) from the original on 2017-08-09.
  14. PMID 29139533
    .
  15. PMID 7474221
    .
  16. PMID 16702348
    .
  17. PMID 9892328
    .
  18. PMID 11411265
    .
  19. S2CID 29977127
    .
  20. ^ a b c d e f g h "Homocysteine". www.thedoctorsdoctor.com. Archived from the original on 2008-12-05. Retrieved 2008-11-22.
  21. ^ a b Adëeva Nutritionals Canada > Optimal blood test values Archived 2009-05-29 at the Wayback Machine Retrieved on July 9, 2009
  22. ^ a b c d e f g h Derived from molar values using molar massof 135 g/mol
  23. ^ "Hyperhomocysteinemia - Hematology and Oncology - Merck Manuals Professional Edition". merckmanuals.com. Archived from the original on 2017-06-09.
  24. S2CID 13228673
    .
  25. S2CID 20443022
    .
  26. S2CID 7689901
    .
  27. PMID 20838622
    .
  28. PMID 22270909
    .
  29. S2CID 22853996
    .
  30. PMID 15141041
    .
  31. PMID 11145936
    .
  32. PMID 18056804
    .
  33. S2CID 45945199
    .
  34. PMID 25590290
    .

External links

Wikiversity has learning resources about Homocysteine
Retrieved from "https://en.wikipedia.org/w/index.php?title=Homocysteine&oldid=1186054534"