some glucose bypasses liver to provide fuel for brain anderythrocytes• in hepatocytes– glucose is actively phosphorylated• by the action of glucokinase– glucose‐6‐phosphate may be converted to:• glycogen to replenish liver stores• glucose via glucose‐6‐phosphatase if blood glucose < 4 mM• pyruvate via glycolysis, hence to acetyl‐CoA, but fatty acids are preferredfuel for liver cells• PPP intermediates providing NADPH for reductive biosyntheses andpentose phosphates for nucleotide biosynthesis

Glycolysis and gluconeogenesis are tightly regulated, opposing metabolic pathways that help control blood glucose levels.  Glycolysis converts glucose to two pyruvate molecules, whereas gluconeogenesis consumes a net total of 6 NTPs (4 ATPs and 2 GTPs) to convert two pyruvate molecules back to glucose.  When glycolysis is upregulated, gluconeogenesis is downregulated, and vice versa.As shown in Figure 1, glycolysis and gluconeogenesis in the liver are largely regulated by the allosteric action of the small molecule fructose-2,6-bisphosphate (F2,6BP) on the enzymes phosphofructokinase-1 (PFK-1) and fructose-1,6-bisphosphatase (F1,6BPase).  PFK-1 is a kinase that uses ATP to phosphorylate fructose-6-phosphate (F6P) in an irreversible step of glycolysis, forming fructose-1,6-bisphosphate (F1,6BP) and ADP.  During gluconeogenesis, F1,6BPase removes the phosphate group by hydrolysis.Figure 1  Activities of (A) PFK-1 and (B) F1,6BPase on their respective substrates in the presence (solid lines) and absence (dashed lines) of F2,6BPA bifunctional enzyme that contains a phosphofructokinase-2 (PFK-2) domain and a fructose-2,6-bisphosphatase (F2,6BPase) domain controls F2,6BP levels in the liver.  The PFK-2 domain converts F6P to F2,6BP, and the F2,6BPase domain converts F2,6BP back to F6P.  When blood glucose levels are low, the enzyme becomes phosphorylated.  This phosphorylation event simultaneously activates the F2,6BPase domain and inactivates the PFK-2 domain.  Under high blood glucose conditions, the enzyme becomes dephosphorylated, activating the PFK-2 domain and inactivating the F2,6BPase domain.Question 13Which metabolic process most likely provides the energy necessary for sustained gluconeogenesis?A.Fatty acid oxidationB.GlycogenolysisC.FermentationD.Pentose phosphate pathway

In glycolysis, glucose is converted toMultiple Choicepyruvate.NAD+ and ADP.citrate.acetyl CoA.CO2 and H2O.

In the liver, insulin signalling up-regulates glycolysis. Which of the following signalling pathways explains that mechanism?Group of answer choicesIt activates protein phosphatase-1 which dephosphorylates glycogen phosphorylase.It results in the activation of cAMP dependent protein kinase A (PKA) which phosphorylates pyruvate kinase.It activates the expression of hexokinase, PFK-1 and pyruvate kinase.It results in an increased expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase.

Which of the following regulatory mechanisms helps increase net glucose catabolism in the liver after a meal?A.Inhibition of hexokinase by glucose-6-phosphateB.Allosteric suppression of phosphofructokinase-1 by ATP bindingC.Hormonal suppression of fructose-2,6-bisphosphate synthesisD.Allosteric inhibition of fructose-1,6-bisphosphatase activity

Dietary carbohydrates are used to synthesize liver glycogen, which exists as particles of various sizes.  During the synthesis of a new glycogen particle, a glucose molecule is linked to the protein glycogenin, after which additional glucose molecules are linked to the first glucose and to each other to form regions that are successively farther from glycogenin.  Glycogen synthesis is catalyzed by the enzyme glycogen synthase, whose activity is inhibited by phosphorylation of three carboxy-terminal serine residues.  During the postabsorptive state (ie, after carbohydrate absorption from a meal is finished), hormone-stimulated release of glucose residues from liver glycogen stores help maintain adequate glucose levels in the blood.Although the important role of liver glycogen in whole-body glucose metabolism has long been appreciated, much remains unknown about the regulation of liver glycogen synthesis and breakdown.  Based on previous studies suggesting a relationship between glycogen particle size and the rate of glycogenolysis, a team of researchers measured the average sizes of liver α and β glycogen particles in wild-type (WT) mice (Table 1).Table 1  Dimensions of Liver Glycogen ParticlesTo better understand the role of the protein glycogenin in glycogen synthesis, the researchers also mated male and female mice that were heterozygous for glycogenin expression (GN +/−) to produce heterozygous offspring as well as mice with WT and knockout (GN −/−) genotypes.  Relative glycogenin gene expression (ie, mRNA levels) was measured in liver and heart samples from the mice (Table 2).  Glycogenin was undetectable in western blots of tissue samples from knockout mice.Table 2  Gene Expression (mRNA Levels Relative to WT) in Liver and Heart Samples.The researchers also measured glycogen concentrations in liver and heart samples from the mice.  The results are presented in Figure 1.Figure 1  Liver and heart glycogen concentrations Question 12The glucagon-induced entry of glucose derived from liver glycogen into the bloodstream for transport to other tissues involves close interaction among which enzymes?A.Glycogen phosphorylase, debranching enzyme, glycogen synthaseB.Glycogen phosphorylase, debranching enzyme, phosphoglucomutase, glucose 6-phosphataseC.Debranching enzyme, phosphoglucomutase, glycogen synthaseD.Debranching enzyme, phosphoglucomutase, phosphofructokinase, glucose 6-phosphatase