4: Fuel for Now

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Learning objectives

Glycolysis and the pyruvate dehydrogenase complex

Compare the \(K_m\)s of glucokinase and hexokinase and relate this activity to their tissue specific activity.
Determine flux through glycolysis based on the regulation of phosphofructokinase 1 and 2 (PFK1 / PFK2), pyruvate kinase (PK), and the pyruvate dehydrogenase complex.
Describe the regulation and necessary cofactors of the pyruvate dehydrogenase complex (PDC).

Tricarboxylic acid cycle (TCA) and electron transport chain (ETC)

Describe the impact of the ratio of NADH/NAD⁺ and ATP/ADP on flux through the tricarboxylic acid cycle (isocitratedehydrogenase and α-ketoglutarate) and the ETC.
Determine the relevance of the TCA cycle for providing key intermediates to other synthetic pathways (i.e. heme synthesis) and the need to replenish TCA cycle intermediates.
Evaluate the role of the malate-aspartate shuttle and the glycerol 3-phosphate shuttle in transferring NADH across the mitochondrial membrane.
Determine the impact of inhibitors and uncouplers on the ETC.

Fatty acid synthesis

Describe fatty acid synthesis, including the location of the pathway, substrate, and regulation of acetyl-CoA carboxylase.

Glycogen synthesis

Determine how glycogen synthesis is regulated in the liver and skeletal muscle (key enzyme: glycogen synthase).

This chapter will focus on the pathways involved fuel usage in the fed state. Under these conditions, insulin is elevated and glucose uptake by most tissues is increased. The increase in fuel availability enhances both ATP production and fuel storage. Whether fuel is oxidized or stored depends on the regulation of various hepatic pathways (glycolysis, tricarboxyilc acid cycle (TCA), electron transport chain (ETC), fatty acid synthesis, and glycogen synthesis), and they all act in concert to maintain metabolic efficiency. The most important part of each of these pathways will be understanding the key regulatory enzymes and how flux can be altered through these regulatory mechanisms.

Thumbnail: Grey, Kindred, Chapter 4. 2021. CC BY 4.0.