Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

161
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
161
Translation01:31

Translation

14.7K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
14.7K
Mismatch Repair01:20

Mismatch Repair

4.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.8K
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Medical Biochemistry And Metabolomics
  9. Metabolic Medicine
  11. The Common Homocystinuria-associated P1173l Variant Of Human Methionine Synthase Impairs Reductive Methylation

The common homocystinuria-associated P1173L variant of human methionine synthase impairs reductive methylation

Arkajit Guha1, Ruma Banerjee1

  • 1Department of Biological Chemistry, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109.

The Journal of Biological Chemistry
|June 13, 2025

Related Experiment Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

646
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

33.7K
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

2.6K

View abstract on PubMed

Summary
This summary is machine-generated.

The P1173L mutation in human methionine synthase (MTR) impairs its function, especially with physiological repair systems. Small molecule electron donors may offer therapeutic benefits for homocystinuria patients with this MTR variant.

Area of Science:

  • Biochemistry
  • Enzymology
  • Molecular Biology

Background:

  • Human methionine synthase (MTR) is crucial for folate and one-carbon metabolism.
  • MTR is vulnerable to oxidative damage, requiring methionine synthase reductase (MTRR) for repair.
  • The P1173L MTR variant causes homocystinuria, linked to cardiovascular disease.

Purpose of the Study:

  • To investigate the biochemical and kinetic effects of the common P1173L MTR mutation.
  • To explore strategies for overcoming expression challenges and understanding MTR variant function.
  • To identify potential therapeutic interventions for P1173L-associated homocystinuria.

Main Methods:

  • Co-expression of MTR with the MMADHC chaperone for soluble protein production.
  • In vitro kinetic assays using artificial and physiological reducing systems (MTRR/NADPH).

Related Experiment Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

646
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

33.7K
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

2.6K
  • Electron Paramagnetic Resonance (EPR) and pre-steady state kinetic analyses.

    • Main Results:

    • Co-expression with MMADHC facilitated full-length human MTR expression.
    • P1173L MTR showed similar activity to wild-type with artificial systems but was significantly less active with MTRR/NADPH.
    • The mutation altered the rate-limiting step in MTRR-mediated reactivation, with electron transfer becoming rate-limiting.

    Conclusions:

    • The P1173L mutation imposes pleiotropic effects on MTR function, particularly impacting its reactivation by MTRR.
    • Electron transfer from MTRR to cob(II)alamin is identified as a key bottleneck for the P1173L variant.
    • Small molecule electron donors may represent a viable therapeutic strategy for homocystinuria patients with the P1173L MTR mutation.