NDLI: Metabolic engineering of lactate dehydrogenase rescues mice from acidosis

Content Provider	PubMed Central
Author	Acharya, Abhinav P. Rafi, Mohammad Woods, Elliot C. Gardner, Austin B. Murthy, Niren
Copyright Year	2014
Abstract	Acidosis causes millions of deaths each year and strategies for normalizing the blood pH in acidosis patients are greatly needed. The lactate dehydrogenase (LDH) pathway has great potential for treating acidosis due to its ability to convert protons and pyruvate into lactate and thereby raise blood pH, but has been challenging to develop into a therapy because there are no pharmaceutical-based approaches for engineering metabolic pathways in vivo. In this report we demonstrate that the metabolic flux of the LDH pathway can be engineered with the compound 5-amino-2-hydroxymethylphenyl boronic acid (ABA), which binds lactate and accelerates the consumption of protons by converting pyruvate to lactate and increasing the NAD+/NADH ratio. We demonstrate here that ABA can rescue mice from metformin induced acidosis, by binding lactate, and increasing the blood pH from 6.7 to 7.2 and the blood NAD+/NADH ratio by 5 fold. ABA is the first class of molecule that can metabolically engineer the LDH pathway and has the potential to have a significant impact on medicine, given the large number of patients that suffer from acidosis.
Related Links	http://dx.doi.org/10.1038/srep05189
Starting Page	5189
File Format	PDF
ISSN	20452322
e-ISSN	20452322
Journal	Scientific Reports
Volume Number	4
Language	English
Publisher	Nature Publishing Group
Publisher Date	2014-06-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Science and technology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Metabolic engineering of lactate dehydrogenase rescues mice from acidosis

The Tie2-agonist Vasculotide rescues mice from influenza virus infection

Metabolic acidosis due to D-lactate.

Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose

Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase

Engineering a d-lactate dehydrogenase that can super-efficiently utilize NADPH and NADH as cofactors

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice

Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein

Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle

Metabolic engineering of lactate dehydrogenase rescues mice from acidosis

Similar Documents

Metabolic engineering of lactate dehydrogenase rescues mice from acidosis

The Tie2-agonist Vasculotide rescues mice from influenza virus infection

Metabolic acidosis due to D-lactate.

Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose

Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase

Engineering a d-lactate dehydrogenase that can super-efficiently utilize NADPH and NADH as cofactors

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice

Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein

Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle

Metabolic engineering of lactate dehydrogenase rescues mice from acidosis