Flavin adenine dinucleotide

So moreover, Amino acids, remember glutamine, metabolize to produce intermediates also for the TCA pathway.

You have glutaminase that converts glutamine to glutamate, which is then transported in the mitochondria, then mitochondrial glutamate transporter, and that's used in the TCA via transamination to alpageta glutamate, right? And just also, you should always remember the TCA oxidizes those nucleotides, NADH and FADH2, driving electrons and proton motor force, ultimately reducing molecular oxygen to H2O, so that the electron transport chain sustains oxidative phosphorylation through complex bonds.

Okay.

And also remember the TCA pathway will produce citrate.

whether or not the T cell has to be activated only or further differentiated or indeed even proliferated.

So there is a final optimum balance of bioenergetic ATP production the interactive pathways so that there is a plenum of biosynthetic intermediates.

And of course, the redox pose, for example, NAD to NADH, FAD to FADH2, NADP to NADPH, has to be set for all of those physiological events to occur, such as activation, differentiation, proliferation, see? So a quiescent T-cell, must have basal bioenergetic needs that are always going to be supported by some oxidative phosphorylation.

And that can be fueled by fatty acid oxidation.

And then AMP as well, if it's depleted, means that you are now in a a demand for ATP biogenesis.

That means you're going to have AMP kinase turning on the kind of intermediary metabolism that's going to be promoting, for example, beta-oxidation, which would then generate a lot of NADH and FADH2, which would reoxidize the electrical transport chain, and then ultimately going through COPLEX-5 would generate more ATP in the mitochondria.

You see? So hexokinases, another important enzyme, important for mycolysis.

You know that many hexokinases, but not the particular one in liver, and also in some immune cells, known as glucokinase, catalyzes the same reaction, phosphorylation of glucose in sick position.

When oxygen is available, the second pathway activates, pyruvate enters the mitochondrion and is converted to acetyl-CoA, which then enters the TCA cycle.

The TCA cycle oxidizes acetyl groups and generates NADH and FADH2, electron carriers that power the third pathway, the electron transport chain.

This chain uses the electrons from NADH and FADH2 to pump protons across the inner mitochondrial membrane, creating an electrochemical gradient that drives ATP synthase, producing approximately 30 to 32 ATP molecules per glucose molecule under optimal conditions.

The three-step cascade from glucose to ATP extracts approximately 38 ATP per glucose molecule under aerobic conditions, representing the most efficient metabolic pathway available to human cells.

Biochemistry Consensus, Standard Textbooks, and Votenvote's Biochemistry Pathway 4.

So there's a mismatch between the stress and the activity that we're doing.

And therefore, because you're just sitting around, there's excessive substrate coming to your mitochondria, and therefore you're gonna make a lot of the reducing agents, the NADH and the FADH2.

But there's no ATP demand.

ATP is the energy.

Now, before entry into the mitochondria, beta-acyl-CoAs regulate cytosolic metabolism via allosteric and non-allosteric mechanisms.

Since the products of fatty acid oxidation include, of course, NADH and FADH2, which are then used to drive ATP synthesis and thus support gluconeogenesis, for example, in a fasting liver, what effect would you expect cytosolic fatty acyl-CoA would have on phosphofractor kinase 1 in the fasting liver? So that's a question you can answer on your own.

Obviously, this is a recorded lecture series, so you're not going to be able to answer it right now, but I want you to think about that.

And you know, we have a podcast email, authenticbiochemistry at gmail.com. You can send me your detailed answers, and I'd be glad to respond to those emails.

The first reaction, FAD, is the electron acceptor.

So FAD goes to FADH2 that generates enoyl CoA.

Then Water is added.

And what occurs here is 3L-hydroxyacyl-CoA is generated.

Oxidation, hydration, another oxidation, then cleavage.

So each cycle produces FADH2 and NADH, which feed into the electron transport chain to generate ATP.

For example, a common like 18 carbon fatty acid requires 18 complete cycles of beta oxidation.

Even if a lot of that to you is kind of like word salad, what you should be hearing is like this shit has to go through a lot of cycles before your body can meaningfully use it.

The final energy production step is the acetyl-CoA enters the citric acid cycle, shout out our old friend the Krebs cycle, producing more NADH and FADH2.

These electron carriers power oxidative phosphorylation in the electron transport chain.

So the final yield here is a 16-carbon fatty acid, which produces about 106 NADH.

The inner mitochondrial membrane contains four fixed protein complexes that form the backbone of the electron transport chain.

Complex 1 accepts electrons from NADH, while complex 2 accepts them from FADH2.

Neither complex can pass electrons directly to complex 3.

Instead, both hand their electrons to CoQ10, which performs a fundamentally different role than static membrane proteins.