pyruvate dehydrogenase acetyl CoA
FIGURE 6 Regulation of PEP formation by protein kinase A (cyclic AMP-dependent protein kinase). Protein kinase A catalyzes the phosphorylation and, hence, inactivation of pyruvate kinase whose activity limits the conversion of PEP to pyruvate.
accelerated by cyclic AMP-dependent phosphorylation of CREB (see Chapter 2).
Lipogenesis and Ketogenesis
An alternate fate of pyruvate in mitochondria is decarboxylation to form acetyl CoA (Fig. 7). This
2-carbon acetyl unit is the building block of fatty acids and eventually finds its way back to the cytosol where fatty acid synthesis (lipogenesis) takes place. Lipogenesis is the principal competitor of gluconeogenesis for
3-carbon precursors. The first committed step in fatty acid synthesis is the carboxylation of acetyl CoA to form malonyl CoA. Acetyl CoA carboxylase, the enzyme that catalyzes this reaction, is yet another substrate for protein kinase A and is powerfully inhibited when phosphorylated. Inhibition of fatty acid synthesis not only preserves substrate for gluconeogenesis but also prevents oxidation of glucose by the hexose monophosphate shunt pathway (Fig. 3). NADP, which is required for shunt activity, is reduced in the initial reactions of this pathway and can be regenerated only by transferring protons to the elongating fatty acid chain.
Fatty acid synthesis and oxidation constitute another substrate cycle and another regulatory site for cyclic AMP action. The same reaction that inhibits fatty acid synthesis promotes fatty acid oxidation and consequently ketogenesis (ketone body formation) (Fig. 7). Long-chain fatty acid molecules that reach the liver can either be oxidized or esterified and exported to adipose tissue as the triglyceride component of low-density lipoproteins. To be esterified, fatty acids must remain in the cytosol, and to be oxidized they must enter the mitochondria. Long-chain fatty acids can cross the mitochondrial membrane only when linked to carnitine.
Carnitine acyl transferase, the enzyme that catalyzes this linkage, is powerfully inhibited by malonyl CoA. Thus when malonyl CoA concentrations are high, coincident with fatty acid synthesis, fatty acid oxidation is inhibited. Conversely, when the formation of malonyl CoA is blocked, fatty acids readily enter mitochondria and are oxidized to acetyl CoA. Because long-chain fatty acids typically contain 16 and 18 carbons, each molecule that is oxidized yields eight or nine molecules of acetyl CoA. The ketone bodies ft-hydroxybutyrate and acetoacetate are formed from condensation of two molecules of acetyl CoA and the subsequent removal of the CoA moiety.
By reducing the concentration of malonyl CoA, glucagon sets the stage for ketogenesis, but the actual acetyl CoA carboxylase P (inactive)
acetyl CoA carboxylase P (inactive)
Was this article helpful?
One of the main home remedies that you need to follow to prevent gallstones is a healthy lifestyle. You need to maintain a healthy body weight to prevent gallstones. The following are the best home remedies that will help you to treat and prevent gallstones.