9 - Glycogenesis

• What types of fuels to most cells derive energy from?

  Carbohydrates, Amino acids and Fatty acids
• Which of these is the major source of energy?

  Fatty acids, which are degraded in mitochondria to Acetyl-CoA and enter the citric acid cycle
• What cells rely on glucose as their main source of energy?

  Cells which do not posses mitochondria (red blood cells) and cells which have relatively few (skeletal muscle), as they have a reduced ability to use fatty acids as fuels
• Approximately how much carbohydrate is consumed a day?

  Around 300g of starch, consisting of a mixture of amylose and amylopectin
• Describe the digestion of carbohydrates

  - Begins in the mouth with salivary amylase which breaks alpha 1,4 bonds

  - Pancreatic juice contains 2 alpha amylases

  - Cells of the intestinal villi secrete CHO degrading enzymes, a(1,6)glucosidase, maltase, sucrase and lactase
• What percentage of dietary starch is broken down before the stomach?

  50%
• What is amylose broken down into by amylase?

  Maltotriose and Maltose
• What is amylopectin broken down into by amylase?

  Alpha-limit dextrins
• What makes amylopectin district from amylose?

  The alpha 1,6 glycosidic bond
• What ions does amylase complex with?

  Ca2+ and Na+
• What cells of the intestinal mucosa absorb monosaccharides?

  Enterocytes
• What is the function of the brush border?

  To maximise surface area for glucose uptake
• How are monosaccharides transported across the lipid bilayer?

  - Glucose and Galactose are actively transport red across the membrane by SGLT1 with Na+

  - Fructose is transported via facilitated diffusion with GLUT5

  - Modnosaccarides exit cell via facilitated diffusion with GLUT2

  - Co-transport allows glucose uptake with SGLT1
• What vein do the monosaccharides eventually enter?

  The hepatic portal vein , which leads to the liver
• Explain how the liver acts as a first pass organ

  It acts as a buffer for glucose, and is the major organ for controlling glucose homeostasis
• What is glucose uptake into liver cells facilitated and determined by?

  Facilitated by GLUT2 and determined by relative concentrations inside and outside of cells
• Describe the GLUT2 transporter

  - High capacity but low affinity for glucose

  - This means it can only uptake rapidly when blood glucose is high
• What happens to the glucose in hepatocytes?


  It is phosphorylated by glucokinase, which effectively traps the glucose inside the cell, where it can then be stored as glucogen or metabolised to produce ATP by glycolysis
• For what reasons is Glucose phosphorylated to form Glucose-6-phosphate?

  - Prevent it from passing out of the cell

  - To prepare it for storage storage by Glycogenesis or break down by Glycolysis
• What enzyme catalyses this reaction?

  In the liver, Glucokinase, but in the muscle and other tissues Hexokinase
• Describe the differences between the Glucokinase and Hexokinase isoenzymes

  - Glucokinase is a low affinity and high capacity enzyme

  - Hexokinase is a high affinity enzyme
• Why is this useful for their specific functions?

  - Hexokinase has a very high affinity but a lower maximal capacity

  - Glucokinase has a low affinity and much higher capacity

  - This means when muscle cells have taken up the glucose they need, the liver can take up glucose for storage
• About how much free glucose is present in the blood and tissue fluid?

  12g
• How much glucose does the brain need per hour?

  5-6g, over 70% of the total glucose usage by the body
• Therefore, how long would circulating glucose support us for if not continuously replenished?

  2 hours
• Describe glycogen


  It is an extremely branched polysaccharide used for the storage of glucose. Has a helical structure and is semi-soluble
• What is the process of Glycogenesis?

  creation of glycogen from glucose molecules
• What is the process of Glycogenolysis?

  breakdown of glycogen into glucose
• What makes up the protein core of Glycogen?

  Glycogenin
• What bonds are found in Glycogen?

  Alpha 1-4 glycosidic bonds and alpha 1-6 branches
• Approximately how many 1-6 links are there compared to 1-4 links?

  1 1-6 per 10 1-4
• How is Glycogen stored?

  - It is synthesised from glucose-6-phosphate and can be rapidly broken down to give this

  - It is stored within tissues as glycogen granules, mostly in liver and muscle cells
• Describe step 1 of glycogen synthesis

  Glucose-6-Phosphate is converted to Glucose-1-phosphate by Phosphoglucomutase
• Describe step 2 of glycogen synthesis

  Glucose-1-phosphate is combined with UTP to form Uridine diphosphoglucose, which is activated to enable encorporation into glycogen chains

  - This reaction is catalysed by UDP-Glucose Pyrophosphorylase
• Describe step 3 of glycogen synthesis

  Glycogen synthase catalyses the addition of UDP-glucose onto the glycogen chain
• Why is this step the most important step?

  Because it is regulated
• What is step 4 of glycogen synthesis?

  Branching
• What is this step catalysed by>

  Amylo(1,4>1,6)transglycosylase, or 'branching enzyme
• Describe step 4


  Branching enzyme cleaves off 7 linked units and transfers the chain to a different glucose moity, forming a 1-6 glycosidic linkage