Related Experiment Video

Updated: Aug 8, 2026

Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging
11:43

Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging

Published on: December 30, 2016

Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency

Kristen Berendzen1, Douglas W Theriaque, Jonathan Shuster

  • 1Division of Endocrinology and Metabolism, Department of Medicine, University of Florida College of Medicine, P.O. Box 10226, Gainesville, FL 32610, USA. berenkm@medicine.efl.edu

Mitochondrion
|May 27, 2006
PubMed

Insights

Oral dichloroacetate (DCA) effectively reduced lactate levels in children with pyruvate dehydrogenase complex (PDC) deficiency. This treatment was well-tolerated and may improve cellular energy metabolism, warranting further controlled studies.

Area of Science:

  • Biochemistry
  • Pediatric Medicine
  • Metabolic Disorders

Background:

  • Congenital lactic acidosis is a severe condition often caused by pyruvate dehydrogenase complex (PDC) mutations.
  • Current treatment options for PDC deficiency are limited, highlighting the need for effective therapies.

Purpose of the Study:

  • To evaluate the efficacy and tolerability of oral dichloroacetate (DCA) in treating children with congenital lactic acidosis due to PDC mutations.
  • To explore DCA's potential mechanism of action in improving cellular energy metabolism.

Main Methods:

  • Retrospective analysis of case histories from 46 pediatric subjects diagnosed with PDC deficiency.
  • Assessment of clinical presentation, diagnosis, and response to oral DCA treatment, including lactate levels.

Main Results:

  • Oral DCA administration led to significant reductions in blood and cerebrospinal fluid lactate concentrations.
  • The treatment was generally well-tolerated by the pediatric subjects.
  • DCA demonstrated potential in stimulating residual enzyme activity in PDC-deficient patients.

Conclusions:

  • Oral DCA is a promising therapeutic agent for children with congenital lactic acidosis caused by PDC deficiency.
  • DCA may enhance cellular energy metabolism by activating residual PDC enzyme activity.
  • A controlled clinical trial is necessary to confirm DCA's definitive role in managing this disease.

More Related Videos

Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals05:59

Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals

Published on: May 19, 2023

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase05:51

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase

Published on: December 19, 2011

Related Concept Videos

Fates of Pyruvate01:20

Fates of Pyruvate

Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Depolarizing Blockers: Pharmocokinetics01:19

Depolarizing Blockers: Pharmocokinetics

Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
Loss of Carboxy Group as CO2: Decarboxylation of β-Ketoacids01:02

Loss of Carboxy Group as CO2: Decarboxylation of β-Ketoacids

Carboxylic acids, upon heating, undergo a decarboxylation reaction by releasing carbon dioxide gas. Monocarboxylic acids do not undergo decarboxylation easily. However, a silver salt of carboxylic acid reacts with bromine or iodine under high temperature to release carbon dioxide gas and forms halide with one less carbon. This reaction is called the Hunsdiecker reaction.