In this podcast I cover basic energy metabolism within the cell, with particular emphasis on how the mitochondria play a role. I also discuss the NAD+/NADH and things that lead to the age-related decline in the NAD+ pool and how circadian rhythms fit in to the picture. Below are the pictures and outline for this podcast to follow along with.
- Energy metabolism in the cytosol
- What is a redox pair?
- NAD+/NADH, FAD/FADH2
- Glycolysis yields pyruvate or lactate, 2 ATP and 2 NADH
- Dependent on the rate of energy production
- Pyruvate & NADH are shuttled in to the mitochondria
- Lack of O2 or mitochondria leads to lactate accumulation
- Pyruvate and lactate are only metabolized in the mitochondria
- What is a redox pair?
- Energy metabolisms in the mitochondria (~30 ATP from glucose, >100 ATP from fatty acids
- Pyruvate/lactate converted to Acetyl CoA
- The citric acid cycle(Krebs cycle, tricarboxylic acid cycle, TCA cycle)
- Uses NAD+, NADH enters ETC
- Beta oxidation of fatty acids
- Acetyl CoA Feeds in to the TCA cycle
- FADH2 enters the ETC
- Electron transport chain(ETC)
- NADH and succinate generated via TCA cycle
- System-wide energy metabolism
- During exercise, working muscles make lactate to maintain high cytosolic NAD+/NADH ratio
- Lactate is either:
- Transported to the mitochondria of that muscle cell, converted to pyruvate then Acetyl CoA to enter the TCA
- Kicked out of that muscle cell and transported to another local muscle cell to enter its mitochondria
- Enters the circulation and Metabolized by the brain, heart, and other muscles
- Converted to glucose in the liver, kidney, and gut
- Lactate can form due to high energy demand or high glucose supply
- Factors affecting NAD+ availability
- Synthesis occurs via de novo production from tryptophan as well as the salvage pathway
- PARP1(Poly [ADP-ribose] polymerase 1)-DNA repair
- NAD to NAM
- CD38-PM anchored enzyme, involved in inflammation, induced by endotoxin
- NAD to NAADP
- Sirtuins (1-7)-DNA repair, Epigenetics(Deacetylase), cell metabolism, increase NAD+ biosynthesis. Converts NAD to NAM. SIRT3-5 in mitochondria
- Activated by fasting
- Replenish NAD+ levels via the salvage pathway
- Regulate NAMPT(Nicotinamide phosphoribosyltransferase) (SIRT1 cytoplasm, nucleus)-NAM to NMN
- Loss of NAD+ from any of these pathways decreases energy metabolism(We need NAD+/NADH and these pathways form something else)
- Fasting induces SIRT1 to ramp up the salvage pathway and increases the NAD+/NADH because you’re not using energy