Question

1. Consider that a molecule of glutamate can be converted to alpha ketoglutarate by the reaction seen below:

glutamate + NAD+ --> alpha-ketoglutarate + NADH + NH3+

what are the net use or production of NADH and FADH2?

iN THE LIVER, what is the net production or consumption of ATP (including ATP equivalents) under typical mitochondrial conditions if any net gain of NADH and FADH2 can be used by the electron transport chain? show work for credit.

Answer 1

First we have to understand what is NADH and FADH2 and what is use in the liver

Fatty liver disease (FLD), the most common chronic liver disease in the United States, may be caused by alcohol or the metabolic syndrome. Alcohol is oxidized in the cytosol of hepatocytes by alcohol dehydrogenase (ADH), which generates NADH and increases cytosolic NADH/NAD⁺ ratio.

Alpha-ketoglutarate dehydrogenase (α-KGDH) is a highly regulated enzyme, which could determine the metabolic flux through the Krebs cycle.

It catalyses the conversion of α-ketoglutarate to succinyl-CoA and produces NADH directly providing electrons for the respiratory chain.

α-KGDH is sensitive to reactive oxygen species (ROS) and inhibition of this enzyme could be critical in the metabolic deficiency induced by oxidative stress.

Aconitase in the Krebs cycle is more vulnerable than α-KGDH to ROS but as long as α-KGDH is functional NADH generation in the Krebs cycle is maintained. NADH supply to the respiratory chain is limited only when α-KGDH is also inhibited by ROS. In addition being a key target, α-KGDH is able to generate ROS during its catalytic function, which is regulated by the NADH/NAD⁺ ratio.