NAD+ regeneration - anaerobic glycolysis/fermentation & the Cori cycle
Glycolysis is wimpy compared to oxidative phosphorylation when it comes to ATP generation, but it’s better than nothing! So, when oxygen is limited (like in active muscles), preventing oxphos, or if you don’t have mitochondria (like is the case for red blood cells (erythrocytes)), you turn to anaerobic fermentation, relying solely on glycolysis for ATP. Glycolysis doesn’t need oxygen, but it does need NAD+, and it doesn’t need (in fact, it’s actually inhibited by) NADH. Glycolysis uses up NAD+ and generates NADH, so if you want to keep glycolysis going, you need to regenerate NAD+, which you can do by passing the electrons from NADH off onto something else - like pyruvate (in lactate fermentation) or acetaldehyde (the decarboxylated form of pyruvate) (in ethanol fermentation which some microbes & plants can do). That fermentation doesn’t produce ATP, but it regenerates the NAD+.
With regards to lactate, if you can then ship that lactate to the liver, the liver can reverse things, regenerating NADH and pyruvate. It could use that pyruvate to get the big ATP payout from the TCA and ETC, but that would deprive the sender cells of energy it started with in that glucose. So, instead, the liver can use gluconeogenesis to make fresh glucose to ship back to the tissues in need. When you get this cycling between muscle and liver, we call it the Cori cycle.
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