Tumor metabolism Flashcards
- What are the regulatory mechanisms contributing to the increased glycolytic activity
of the tumor cells? What are the metabolic advantages of the increased glycolysis?
a) Activation of gene expression (increased transcription-translation): higher levels of glucose transporters and glycolytic enzymes, and pyruvate dehydrogenase kinases. * Activators: HIF1a, PI3K pathway, c-myc
b) Novel enzyme isoforms: phosphofructokinase 2 (PFKB3) isoform. Continuous production of F-2,6-bP, Akt-dependent activity. Independent of insulin/glucagon ratio. Pyruvate kinase M2 isoform: Dimeric-P/Tetrameric, inactive/active ratio oscillating.
b) Regulatory role of PEP and consequences
c) Akt kinase: glycogen synthesis
d) Glycolitic intermediates vs. ATP production
e) Glycerol-3-P: phospholipids, serine – membranes and nucleotides
f) Pentose-P – NADPH (higher level of glycolytic enzymes + alternative pathway)
What is the role of increased glutaminolysis in tumor cells? How does it work in normoxia and in extreme anoxia?
Normoxia - production of ATP for fatty acid/cholesterol synthesis
Anoxia - production of ATP (Without TCA)
Describe in detail the metabolic processes supporting the increased DNA synthesis of tumor cells!
How are the following molecules produced in sufficiently high quantities in tumor cells?
a) C1 units (NADPH, serine, folic acid)
b) ATP and NADPH (normoxia/hypoxia) – significance of glycolysis and beta oxidation c) amino acids – glycine, glutamine, aspartate
d) ribose-5-P – pentose-P pathway, classical/alternative
e) ornithine, polyamines
f) high level of NAD+ (PARP)
Why do tumor cells need increased fatty acid and cholesterol synthesis? Describe the metabolic pathways that support these in tumor cells!
a) Membranes – phospholipids (fatty acids and glycerol-3-P), plus cholesterol
b) sources of cytoplasmic AcCoA (normoxia, hypoxia)
c) sources of NADPH
d) sources of glycerol-3-P
e) actication of PI3K/Akt pathway – SREBP – cholesterol metabolism
