Biochemical Pathways in Disease: Disruptions and Therapeutic Opportunities

Living cells rely on a complex network of interconnected biochemical pathways to function. These pathways, controlled by enzymes, manage essential cellular processes like energy production and waste removal. Disruptions in these pathways can trigger a series of events leading to disease. This blog post will explore how these disruptions contribute to cancer and metabolic disorders, and how researchers are targeting these pathways to develop new therapies.

Dysfunction in Disease Development

  • Cancer: Cancer arises from genetic and epigenetic alterations that disrupt normal cellular processes. One key culprit is the dysregulation of signaling pathways that control cell growth, proliferation, and death. Mutations in genes encoding proteins like RAS or p53 can lead to uncontrolled cell division, a hallmark of cancer. Additionally, cancer cells rewire their metabolic pathways, favoring a process called aerobic glycolysis even in the presence of oxygen. This shift allows them to generate energy for rapid growth, even in environments with low oxygen.
  • Metabolic Disorders: Disruptions in metabolic pathways can have severe consequences. Inherited disorders like phenylketonuria (PKU) result from mutations in enzymes responsible for breaking down specific amino acids, leading to their toxic build-up. Similarly, type 2 diabetes mellitus (T2DM) involves defects in insulin signaling, compromising the body's ability to regulate blood sugar levels.

Predominant biochemical alterations for progression of type 2 diabetes from insulin resistance and due to beta cells dysfunction.

Targeting Pathways for Treatment

Understanding the molecular basis of these diseases has enabled the development of targeted therapies. Here are some examples:

  • Cancer Therapeutics: Many targeted cancer drugs act on specific proteins within signaling pathways. Tyrosine kinase inhibitors (TKIs) are a prominent class that block the activity of mutated kinases driving cancer cell growth.
  • Metabolic Disease Therapeutics: Enzyme replacement therapy for PKU aims to supplement the missing or dysfunctional enzyme, facilitating the breakdown of the toxic amino acid. Drugs like metformin in T2DM work by enhancing insulin sensitivity and improving glucose uptake into cells.

Tyrosine Kinase-Inhibitor (TKI)-sensitive and-resistant Tumors and the Cellular Consequences. Both TKI-inhibitor sensitive (left panel) and resistant (right panel) tumors display an activating mutation in the EGFR. TKI-inhibitors reduce glucose uptake and suppresses pro-survival signals from PI3K-AKT-mTOR or Ras-Raf-MEK payhways, leading to tumor elimination in TKI-inhibitor sensitive tumors (left panel). On the contrary, tumor can become resistant to EGFR-inhibitors due to a mutation in the ATP-binding site of the EGFR kinase (the target of the inhibitors). The resistant tumors display enhanced glucose uptake and glycolysis. Dong et al now show that PHGDH is upregulated on the gene expression and protein level, which produces serine and replenish antioxidants, nucleotides and DNA damage repair proteins. These events combined promote tumor growth in the EGFR-resistant tumors.

Signaling Pathways: Cellular Communication Channels

Biochemical pathways often converge on and influence signaling pathways. These intricate networks of communication molecules coordinate various cellular processes. Disruptions in these pathways can have cascading effects, contributing to disease development.

Cell Signaling Events

The Future of Biochemical Pathway Research

Research on biochemical pathways continues to unravel the intricate mechanisms underlying disease. By deciphering these pathways, scientists are developing more targeted therapies with the potential to improve disease outcomes and patient lives. Continued exploration of these intricate networks holds immense promise for the future of personalized medicine.

Researchers can benefit from collaborating with reputable suppliers of biochemical reagents, such as Maxanim, to study these pathways. Maxanim offers a vast collection of enzymes, substrates, and other research tools to support investigations into cellular biochemistry and disease mechanisms.

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Biochemical Pathways in Disease: Disruptions and Therapeutic Opportunities
Gen store June 11, 2024
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