An In-Depth Study of TCA cycles, OPA1, S6K1, ATPase, TLR4, MHC-class-I, GCs, and IFNs Bio-Synthesis, and Their Roles of Deficiency in Diabetes, Asthma, Cancer, etc and the NAD Roles in Their Activities

The roles of S6K1 is regulating ATPase, and GTPase synthesis, and consequently the endocytic proliferations including endocytic soluble MHC class II synthesis which regulate both SIRPα1 and TLR4 synthesis , where diabetes reflect deficiency in Ser amino acids that reflect deficiency in pyrimidines synthesis consequently deficiency in Estrogen and reflect increasing in androgen synthesis with increasing in consuming in purines (A&G) that lead to decreasing in anabolic processes which depends on presence of adenosine and guanosine stored in ribosimes.

The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells

Pyruvate occupies a central metabolic node by virtue of its position at the crossroads of glycolysis and the tricarboxylic acid (TCA) cycle and its production and fate being governed by numerous cell-intrinsic and extrinsic factors. The former includes the cell’s type, redox state, ATP content, metabolic requirements and the activities of other metabolic pathways. The latter include the extracellular oxygen concentration, pH and nutrient levels, which are in turn governed by the vascular supply. Within this context, we discuss the six pathways that influence pyruvate content and utilization: 1. The lactate dehydrogenase pathway that either converts excess pyruvate to lactate or that regenerates pyruvate from lactate for use as a fuel or biosynthetic substrate; 2. The alanine pathway that generates alanine and other amino acids; 3. The pyruvate dehydrogenase complex pathway that provides acetyl-CoA, the TCA cycle’s initial substrate; 4. The pyruvate carboxylase reaction that anaplerotically supplies oxaloacetate; 5. The malic enzyme pathway that also links glycolysis and the TCA cycle and generates NADPH to support lipid bio-synthesis; and 6. The acetate bio-synthetic pathway that converts pyruvate directly to acetate. The review discusses the mechanisms controlling these pathways, how they cross-talk and how they cooperate and are regulated to maximize growth and achieve metabolic and energetic harmony.