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Figure 1 | Molecular Cancer

Figure 1

From: A possible primary cause of cancer: deficient cellular interactions in endocrine pancreas

Figure 1

Altered pancreatic beta cell mechanism silencing alpha and delta cells. A: right, anabolic hormones: In hyperglycemia, beta cells release insulin; tyrosine kinase receptors elicit glucose uptake, synthetic processes, cells divide. Enzymes are dephosphorylated: PK, PDH, glycogensynthase are switched on, phosphorylase a, HSL are off; glycogen and lipids increase. These effects are induced via (PKB). Citratesynthase is active, controlled by NADH. Anabolic beta cells turn off with GABA- Zn2+ catabolic alpha cells. A: left, catabolic hormones: In hypoglycemia alpha cells release glucagon; adrenals release epinephrine. GS-coupled receptors activate adenylate cyclase, (PKA) phosphorylates enzymes: phosphorylase a, is switched on, hydrolyses glycogen; glycogensynthase is off. Neoglucogenesis is activated; (PK) and PDH blockade orient the pathway, sparing pyruvate for neoglucogenesis. Glucagon elicits (CRH) (ACTH) release triggering glucocorticoid-cortisol release from adrenals. Cortisol induces muscle proteolysis, providing amino acids for neoglucogenesis. Citratesynthase inhibition spares oxaloacetate for neoglucogenesis. Phosphorylated (HSL) provides fatty acids, giving ketone bodies. B: Cancer hybrid metabolism: GABA release interruption from beta cells, cancels alpha cells inhibition, eliciting a hybrid catabolism-anabolism 1- In tumor cells, insulin induces mitosis and anabolism via PKB; citratesynthase is activate. But glucagon and epinephrine elicit, via PKA, phosphorylation and inhibition of PK and PDH. Low GABA increases epinephrine, inhibits somatostatin; reinforcing Growth Hormone-IGF- insulin actions.

2- In stores, catabolic hormones trigger proteolysis and lipolysis. 3- Metabolism is rewired below PK and PDH bottlenecks: tumor citratesynthase pulls the glucose flux; receiving oxaloacetate via (PEPCK), while acetylCoA comes from ketone bodies or fatty acids oxidized in peroxisomes (their mitochondrial transport is blocked by malonate forming tumor fatty acids via acetylCoA carboxylase). ATPcitratelyase receives the mitochondrial citrate efflux. Diverted from neoglucogenesis, amino acids form tumor proteins, feed lactatedehydrogenase via alanine transamination.

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