Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.1.1 (
hexokinase
)
5,274
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival. The activity of
BAD
, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors. Here we undertook a proteomic analysis to assess whether
BAD
might also participate in mitochondrial physiology. In liver mitochondria,
BAD
resides in a functional holoenzyme complex together with protein kinase A and protein phosphatase 1 (PP1) catalytic units, Wiskott-Aldrich family member WAVE-1 as an A kinase anchoring protein, and glucokinase (
hexokinase
IV).
BAD
is required to assemble the complex in that Bad-deficient hepatocytes lack this complex, resulting in diminished mitochondria-based glucokinase activity and blunted mitochondrial respiration in response to glucose. Glucose deprivation results in dephosphorylation of
BAD
, and
BAD
-dependent cell death. Moreover, the phosphorylation status of
BAD
helps regulate glucokinase activity. Mice deficient for
BAD
or bearing a non-phosphorylatable
BAD
(3SA) mutant display abnormal glucose homeostasis including profound defects in glucose tolerance. This combination of proteomics, genetics and physiology indicates an unanticipated role for
BAD
in integrating pathways of glucose metabolism and apoptosis.
...
PMID:BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. 1293 Nov 74
