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Chapter 5: Glucose Metabolism

1. PURPOSE

  1. This chapter focuses on the main pathways and enzymes that regulate processing of glucose into energy

  2. Think about it as a highway from glucose to ATP, with many entrances and exits to different pathways depending on what the cell needs

  3. Step 1 also likes to ask about how fed/fasting state affects the balance of different pathways, so understanding how pathways connect is key

2. OVERVIEW OF METABOLIC PATHWAYS

  1. On the “highway” of glucose to ATP, the central pathways are the focus of this chapter

  2. Pathways can be generally categorized as “fed-state” or “fasting-state” based on whether they build energy reserves or release energy for later use

  3. We can further break down the processes into 4 main categories

    1. Breakdown of energy sources: Glycolysis; fructose/galactose metabolism; the tricarboxylic acid (TCA) cycle; and oxidative phosphorylation

    2. Storage of energy: Glycogenesis and lipid synthesis

    3. Fasting state metabolism: Gluconeogenesis, lipolysis, glycogenolysis, protein catabolism

    4. Side pathways (other functions): Pentose phosphate pathway (HMP shunt), urea cycle, cholesterol synthesis

  4. Side pathways contribute energy from other sources and/or create energy stores and will be discussed in subsequent chapters

Figure 5-1.

Overview of metabolic pathways.

An illustration shows the multiple metabolic pathways that originate from glucose. Glucose is shown at the top, as the starting point of the pathway. It is shown to undergo glycolysis to form pyruvate, which in turn forms glucose again through gluconeogenesis. The pyruvate is also shown to form lactate through a double-sided resonance arrow. The pyruvate is also shown to form acetyl coenzyme A, which is shown to be involved in the T C A cycle, which is represented by a circular arrow that starts from acetyl coenzyme A and also ends with the arrow pointing toward the same substrate. Another curved arrow branches leftward from the T C A cycle, and this is labeled oxidative phosphorylation. The caption reads, “overview of metabolic pathways.”
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Figure 5-2.

Pathways in fed and fasting states.

Two list-format illustrations detail the different types of metabolic pathways that occur in the fed and the fasting states. The pathways in the fed state is shown in the left side and these include glycolysis, glycogen synthesis, lipid synthesis, and fructose or galactose catabolism. The pathways in the fasting state is shown in the right side and these include gluconeogenesis, glycogenolysis, protein catabolism, lipolysis, and ketone body metabolism. The caption reads, “pathways in fed and fasting states.”
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3. BREAKDOWN OF GLUCOSE

  1. Glucose may enter the cell from outside or be released from intracellular stores (glycogen)

  2. Glycolysis occurs in the cytosol

    1. Glucose is broken down into smaller components

    2. Only 2 molecules of ATP per glucose are produced

    3. Other carbohydrates, glycogen, and lipid metabolites (glycerol) enter the glycolysis pathway

  3. The TCA cycle takes over in the mitochondria when oxygen is present

    1. This produces the intermediates NADH (derived from vitamin B2) and FADH2 (derived from vitamin B3)

    2. Amino acids can also enter into the TCA cycle to supply energy

  4. Oxidative phosphorylation occurs on the inner mitochondrial membrane to turn NADH and FADH2 into ATP

Table 5-1.Glucose facilitators/transporters.
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Table 5-1. Glucose facilitators/transporters.
Protein Insulin-regulated? Tissues
GLUT1 No Red blood cells, cornea, brain, placenta
GLUT2 No β-islet cells, liver, kidney, small intestine. Imports monosaccharides from gut enterocytes into blood.
GLUT3 No Brain, placenta
GLUT4 Yes Adipose tissue, striated muscle
SGLT1 No GI tract, renal reabsorption of glucose from proximal tubule
SGLT2 No Renal reabsorption of glucose (proximal tubule)
Figure 5-3.

Breakdown of glucose.

A flowchart represents the breakdown of glucose across the cell to form pyruvate and then undergo the T C A cycle inside the mitochondria. At the top level glucose is shown to be present extracellularly. This is shown to travel across the plasma membrane into the cytosol, where it converts to glucose-6-phosphate. This in turn is shown to be related by a resonance arrow with fructose-6-phosphate. This in turn forms fructose-1, 6-bisphosphate, which forms glyceraldehyde 3 P, as represented by a resonance arrow. The glyceraldehyde 3 P forms phosphoenolpyruvate, as indicated by another resonance arrow. This phosphoenolpyruvate is shown to form pyruvate, which moves into the mitochondria to undergo the TCA cycle. The pyruvate is also shown to form lactate separately. In the flowchart all the single-direction reaction arrows are colored differently from the resonance arrows and glucose-6-phosphate, fructose-1. 6-bisphosphate, and pyruvate are specifically highlighted. The caption reads “breakdown of glucose.”
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4. GLUCOSE ENTRY INTO THE CELL

  1. Glucose enters the cell through facilitators (GLUT or sometimes SGLT proteins), and the cell needs a way to trap it there so it can't exit the cell

    1. Different cell types use different facilitator ...

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