Questions 26 - 35

1. Questions 26 - 35 Glucose Disposal – The Pathways

2. 26. Parts of Glucose Disposal • Which process requires ATP? • Addition of glucose from UDP-glucose to a growing glycogen chain • Conversion of glucose residues in glycogen to glucose 6-phosphate • ANY of the reactions in the fatty acyl synthase complex (ie, from malonlyl-CoA to fatty acyl-CoA) • Carboxylation of acetyl-CoA to give malonyl-CoA • Decarboxylation of pyruvate to acetyl-CoA once the glucose is activated, no more ATP needed 47 42 6 115 9 phosphorolysis, uses just phosphate energy was invested in making malonyl-CoA yes very catabolic,

3. 27. Choice of G6P fates • Which statement about the balance between glycogenesis and glycolysis in muscle after a carbohydrate meal is CORRECT? • Consumption of ATP in glycogenesis stimulates glycolysis • Insulin stimulates dephosphorylation of phosphofructokinase • Glucose 6-phosphate concentration rises about 100-fold and stimulates glycogen synthase • Production of ATP in glycolysis is the major driving force for glycogenesis • A rise in the level of ATP stimulates glycogen synthase 103 22 44 26 19 Yes, PFK responds to lowering of ATP PFK not regulated by reversible phosphorylation G6P never gets that high in muscle – it inhibits HK demand drives oxidation, not vice versa tempting, but ATP already high and extra glycolysis not likely to make it higher

4. 28. Glucokinase vs Hexokinase • Which statement describes a genuine feature of glucokinase which is NOT shared by hexokinase? • Glucokinase irreversibly produces glucose 6-phosphate from glucose • Glucokinase is inhibited by a build up of glucose 6-phosphate • Glucokinase is stimulated by phosphorylation • Glucokinase can work on any hexoses • Glucokinase is not saturated by 10 mM glucose 18 24 17 17 142 both GK and HK make G6P from glucose – both ‘irreversible’c only HK is inhibited by G6P neither GK nor HK are regulted by reversible phosphorylation only HK can work on any hexose HK is saturated by 1 mM glucose, GK is not even saturated by 10 mM glucose

5. 29. Glycogen Synthesis • Which statement about the synthesis of glycogen from glucose is INCORRECT? • The formation of UDP-glucose is facilitated by the joining of two phosphates to form pyrophosphate • In UDP-glucose, the glucose residue is joined to UDP at the C-1 end of glucose. • Glycogen synthesis occurs in the cytoplasm • Activated glucose residues on UDP-glucose form glycosidic bonds with the C-4 ends of the growing glycogen chain • UTP is regenerated by the reaction of UDP and ATP 86 50 23 27 21 sneaky! pyrophosphate is involve but it is hydrolysed the C1 is the “activated” end most certainly same as B yes. forgot to mention that this year!

6. 30. Glycogen Synthesis • Which statement is CORRECT? • A rise in intracellular glucose concentration is sufficient to increase the rate of glycogenesis in liver • Liver does not have branching enzyme • The size of a glycogen molecule is unlimited in liver • Glucose transport into liver requires insulin • Liver glycogenesis can occur without a concomitant increase in a catabolic pathway it is. Stimulates dephosphorylation of GS 146 7 5 17 39 it does. Liver glycogen and muscle glycogen are the same perhaps less restricted than muscle but not unlimited perhaps less restricted than muscle but not unlimited all anabolic pathways must have a catabolic consequence!

7. 31. Fructose metabolism • Which statement is CORRECT? • Only the liver can dispose of fructose • Fructose is trapped as fructose 6-phosphate in the liver • A fructokinase deficiency would severely deplete ATP levels in liver after a meal containing fructose • The liver cannot convert fructose into glucose • The aldolase involved in liver fructose metabolism is slow in comparison to the rate of fructose trapping muscle can too 11 27 26 16 137 no, as fructose 1-phosphate would just stop trapping and the consumption of ATP F1P to triose phosphates, back up gluconeogenesis this is what causes the ATP depletion

8. 32. Insulin Action - WAT • In white adipose tissue, which process is NOT stimulated by insulin? • The rate of glucose uptake • Pyruvate dehydrogenase activity • Acetyl-CoA carboxylase activity • Expression of fatty acyl synthase • Lipolysis GLUT-4 stimulated 16 16 14 32 143 PDH phosphatase activated the main drive! it is (put down by high fat) inhibited by insulin

9. 33. Lipogenesis – AcCoA transport • Hydroxycitrate is an inhibitor of ATP-citrate lyase. What would be the MOST LIKELY consequence of adding hydroxycitrate to cells undergoing lipogenesis? • The movement of acetyl-CoA into the cytoplasm would decrease • Production of ATP would stop • Mitochondrial acetyl-CoA levels would rapidly deplete • The rate of fatty acid production would increase • Cytoplasmic acetyl-CoA levels would increase. 103 19 47 8 35 ACL aids movement of acetyl CoA to cytoplasm ACL not energy generating acCoA would stay in mito inhibitor of lipogenesis stopping movement out will decrease cytosolic acCoA

10. 34. Pentose Phosphate Pathway • Which statement best describes the relationship between the pentose phosphate pathway (PPP) and lipogenesis? • The PPP produces the glycerol needed for esterification of newly formed fatty acids • Lipogenesis provides glycerol 3-phosphate for the PPP • Lipogenesis uses NADPH produced by the PPP • The PPP provides ATP to fuel lipogenesis • The PPP is necessary to provide the carbon dioxide needed to produce malonyl-CoA 21 3 185 5 3 it doesn’t produce glycerol a nonsense statement true! no ATP made by PPP carbon dioxide not in short supply

11. 35. Fatty Acyl Synthase • Which statement regarding Fatty Acyl Synthase (FAS) is CORRECT? • FAS is inhibited by insulin • The order of reaction in FAS is (in sequence) oxidation, dehydration, and oxidation • FAS decides if a fatty acid is to be desaturated during lipogenesis. Once a saturated fatty acid has been made, it cannot be unsaturated. • FAS incorporates carbon dioxide into the growing fatty acid chain • During the elongation step, the two new carbon atoms are added to the carboxy- end of the growing fatty acid FAS expression stimulated by insulin 17 15 17 14 153 involves reduction FAs can be unsaturated at C9 or less the CO2 that makes malonyl-CoA is lost in FAS reactive unit is the acetyl – growing chain moves to this