ABSTRACT
Abnormal metabolism is an invariant and enduring feature of age-related neurodegenerative disorders that diminish brain function and the ability of the brain to
19.1 Glucose Metabolism Is Diminished in Age-Related Neurodegenerative Diseases. ..................................................................................................... 433
19.2 Reductions in Specic Enzymes May Underlie the Decline in Brain Metabolism in AD. ..................................................................................... 434
19.3 KGDHC is a Central Enzyme of Metabolism with Multiple Functions. .... 435 19.4 Relation of the Subunits or the Number of Copies of Subunits to the
Overall Activity of the Complex Is Unknown. ........................................... 438 19.5 KGDHC is Directly Linked to Cellular NADH and Sulfur Redox State. .. 438 19.6 Free Radicals Generated by the KGDHC Communicate between
Subunits and with Other TCA Cycle Enzymes. ......................................... 439 19.7 KGDHC and Its Subunits Have Multiple Functions. ..................................440 19.8 Reductions in KGDHC, Exaggerated Oxidative Stress, and
Neurodegeneration Are Closely Linked.................................................. 442 19.9 Sensitivity to Oxidants Suggests That KGDHC Is Modied
Posttranslationally in Neurodegenerative Diseases, and This Has Been Demonstrated Directly with Peroxynitrite. ................................................ 443
19.10 Interaction of KGDHC with Calcium is Critical in Neurodegenerative Diseases. .....................................................................................................444
19.11 Pathological and Clinical Implications of Reductions in KGDHC. ...........444 19.12 Reduced Activity of KGDHC Can be Readily Linked to Processing of
