3- Glycogen & Fat

Question 1

• why is glucose the preferred fuel? What cells have an absolute requirement?
• how is glycogen stored & where?
• describe the structure of glycogen.

Answer 1

• because it’s quickly absorbed and can be stored if needed. RBCs, neutrophils, innermost kidney medulla & lens of eye
• stored as granules in the muscles and liver
• has glycosidic 1-6 & 1-4 bonds, polymer of branched chains w many ends so it’s compact but also can be hydrolysed at many ends at the same time

Question 2

Define glycogenesis. Describe
Define glycogenolysis. Describe
-the glycogen stores in liver & muscle serve different functions. elaborate.

Answer 2

• glycogenesis= glycogen synthesis (glycogen + UDP glucose -> glycogen + UDP) enzyme glycogen synthase, synthesis requires energy
• glycogenolysis= glycogen degradation, uses different enzymes to above ie glycogen dephosporylase.
• liver= G6P converted to glucose & exported in blood
• muscle= muscle lacks G6P enzyme so G6P enters glycolysis for energy production.

Question 3

• how is liver glycogen stores regulated by hormones? What are the 2 rate limiting enzymes in synthesis & degradation
• outline glycogen storage disorders.

Answer 3

• glucagon & adrenaline act on glycogen synthase and phosphorylate it to decrease its activity, phosphorylates glycogen phosphorylase to turn on. Insulin acts on glycogen synthase and dephosphorylates it to increase activity, dephosphorylates glycogen phosphorylase to decrease its activity
• glycogen synthesis RLE= glycogen synthase
• glycogen degradation RLE= glycogen phosphorylase
• errors in metabolism, arise from deficiency or dysfunction of enzymes of glycogen metabolism, liver and or muscle can be affected, eg Von Gierke’s is G6P deficiency

Question 4

• outline gluconeogenesis. what are the three majors precursors, is acetyl coA one?
• name the three key enzymes in gluconeogenesis
• how is gluconeogenesis regulated?

Answer 4

• the production of new glucose, beyond 8 hours liver glycogen starts to deplete so we need a new source of glucose
• precursors: 1) lactate (from anaerobic glycolysis in muscles & RBCs), 2) glycerol (released from adipose via breakdown of triglycerides), 3) amino acids (mainly alanine) acetyl coA cannot be converted to pyruvate bc pyruvate dehydrogenase reaction is irreversible so no glucose from acetyl coA
• enzymes= 1)phosphenolpyruvate (PEPCK), 2) fructose 1,6-bisphosphate, 3) glucose-6-phosphate

Question 5

• describe the time course of glucose utilisation
• outline how lipids, including triacylglycerides and adipocytes, are stored.
• briefly outline TAG metabolism & fatty acid synthesis ie lipogensis

Answer 5

• feeding then glucose from food last 2 hrs, 8-10 hrs after feeding, glycogen is broken down to form glucose ie glycogenolysis then 10+ hrs new glucose is made ie gluconeogenesis
• TAGs are hydrophobic so stored in anhydrous form in adipose, utilised in prolonged exercise, pregnancy, mobilised under hormonal control
• adipocytes= large lipid droplet of mainly TAGs,
• TAGs in the S intestine hydrolysed into FAs and Glycerol by pancreatic lipase. Pass into intestinal epithelial cell & recombined to TAG in chylomicron, goes to lymph, then blood to tissues for FA oxidation for energy (not in RBCs) or stored as adipose
• lipogenesis in liver, glucose-> pyruvate in glyc, pyruvate forms acetylCoA & OAA, and condense to form citrate. Citrate to cytoplasm and cleaved back to acetylCoA & OAA. Acetyl coA carboxylase produces malonyl CoA from acetyl coA, FA synthase complex builds new FAs by adding 2C each time provided by malonyl CoA. requires ATP AND NADPH

Question 6

• compare and contract fatty acid oxidation and fatt acid synthesis
• outline how hormonal mobilisation of fat happens
• describe the typical fuel stores in a man of 70kg vs an obese man

Answer 6

• FA oxidation= cycle removes C2, C2 atoms removed as acetyl CoA, produces acetyl CoA, happens in mitochondria, oxidative & produces NADH AND FAD2H, small amount of ATP needed to activate FA, regulated by availability of FAs in mitochondria, insulin inhibits
• FA synthesis= cycle add C2 each time, C2 atoms added as malonyl CoA, consumes acetyl CoA, happens in cytoplasm, reductive so requires NADPH, large amount of ATP needed to drive it, regulated by activity of acetyl CoA carboxylase, insulin stimulates
• lipolysis ie fat mobilisation happens via hormone sensitive lipase. Glucagon and adrenaline phosphorylate and activate HSL, insulin dephosphorylates and inhibits HSL
• TAGs= 15kg, muscle glycogen= 0.3kg, muscle protein= 6kg vs obese TAG= 80kg, muscle protein=6kg