Carbohydrate Metabolism: Pentose Phosphate Pathway

Carbohydrate Metabolism Pentose Phosphate Pathway: While products of glycolysis go off into the rest of the cellular respiration pathway, there is also a branch that goes off to form sugars that make up DNA and RNA, which is known as the Pentose Phosphate Pathway (no energy in the form of ATP is produced or used up) and occurs in the cytosol of the cell The pentose phosphate pathway can use up any glucose-6-phosphate present in the cell (doesn’t have to be made by the first step of glycolysis) → interconversion occurs in the non-oxidative phase, therefore gluconeogenesis cannot occur through the PPP because the oxidative portion of the pathway is irreversible There are 2 main phases of the pathway: The oxidative phase: refers to the breakdown of a molecule where it loses at least one electron (this is made up of 2 irreversible steps) → forms one CO2 and two NADPH molecules and loses one H2O molecule 1. G-6-P is oxidized in order to form lactone and NADPH is produced (after this, a different reaction catalyzed by a second enzyme uses water to form 6-phosphogluconate) 2. A carbon is removed and CO2 is released (electrons reduced from here are used in order to reduce NADP+ to NADPH) forming Ribulose-5-phosphate (the precursor to the sugar that makes up DNA and RNA) The non-oxidative phase: refers to a set of reactions that are reversible, allowing different molecules to enter the pathway in different areas 3. Ribulose-5-phosphate is converted into Ribose-5-phosphate (cyclizes the linear version) 4. Options can occur from here, depending on the cell’s needs. One option is that it can combine with another molecule of ribose-5-phosphate to make a 10 carbon molecule (which is then converted into a 3 and 7 carbon molecule → 3 carbon one can be shipped to glycolysis if need be). Any extra ribose-5-phosphate is reconverted into a sugar and used in metabolic pathways for energy. 5. The 3 and 7 carbon molecules interconvert once more to form a 4 and 6 carbon molecule. The 4 carbon molecule is a precursor to amino acids while the 6 carbon molecule can be used in glycolysis. NADPH is in high concentrations within the cell and is often used in reactions that build molecules (also used in order to give electrons to antioxidants which donate their electrons in order to combat reactive oxygen species) → BIG ROLE IN DONATING ELECTRONS Cellular Respiration Introduction: C6H12O6 + 6O2 → 6CO2 + 6H2O + energy (gross oversimplification of cellular respiration) The energy portion is used in order to generate 38 ATP (heat is also a byproduct of cellular respiration) There is still variation in the amount of ATP (can vary from cell to cell depending on its efficiency) A couple different stages of cellular respiration: 1. Glycolysis which is the breakdown of glucose (6 carbon molecule) to pyruvate (3 carbon molecule) and generates 2 net ATP (makes 4 ATP while using up 2 ATP) 2. Pyruvate oxidation converted pyruvate into acetyl-CoA 3. Krebs cycle (Citric Acid Cycle) takes acetyl-CoA and pumps it into this cycle in order to generate 2 ATP (oxygen is needed) 4. The Electron Transport Chain uses the electron carriers in order to generate 34 ATP (oxygen is needed) Without oxygen, the byproducts of glycolysis are pumped into the fermentation pathway producing lactic acid (other organisms, such as yeast, will produce alcohol) During this entire process, NAD+ and FAD are being reduced to NADH and FADH2 respectively (important in the ETC) Overview of Glycolysis: At first, glucose must be broken down into two 3 carbon molecules (phosphoglyceraldehyde) which ends up using ATP (“investment” phase). This is then followed by the formation of pyruvate which generates 4 ATP (2 net ATP) and 2 NADH molecules per glucose (“payoff” phase) Regulatory steps are steps that are irreversible (such as in the first, third, and final steps) Also, hexokinase is found in most tissues of the body while glucokinase is found in hepatocytes of the liver and beta cells of the pancreas Overall, glycolysis is exergonic (-ΔG) although individual steps can be +ΔG (endergonic) or ΔG (exergonic) Gluconeogenesis: The Big Picture: Our body is able to regulate the amount of glucose found in the blood to a pretty narrow range (~60-150 mg/dL of blood) Fatty acid concentration can range 10 fold levels while blood glucose always stays at a constant range (important because a lot of our cells rely on glucose exclusively to produce ATP) There are two states: a fed state (after you’ve eaten a meal and therefore uses glucose from the meal to go into the blood) and a fasted state (needs a way to get glucose into the blood through two main ways: breakdown of stored glucose in glycogen (located in liver) lasting only 10-18 hours and gluconeogenesis which is the generation of glucose from other carbon molecules, most commonly amino acids and lactate) Gluconeogenesis is almost the exact reverse of glycolysis (since there are those irreversible steps (yellow arrows in the diagram above) because when you go backward, the ΔG is too unfavorable in order to go backwards (need to develop new enzymes in order to go backwards) Gluconeogenesis: Unique Reactions: Instead of using Pyruvate Kinase in the first step of gluconeogenesis, it uses pyruvate carboxylase in order to convert pyruvate (can be generated from lactate if needed) into oxaloacetate (this is why amino acids can be used since they can be broken down into oxaloacetate) and also PEP carboxykinase to convert oxaloacetate into phosphoenolpyruvate (PEP) → uses ATP in the first and GTP in the second Instead of using phosphofructokinase-1, it uses fructose 1,6-bisphosphatase in order to convert fructose 1,6-phosphate to fructose 6-phosphate (uses H2O in order to cleave that phosphate off) Instead of using hexokinase, it uses glucose 6-phosphatase in order to converted glucose 6-phosphate to glucose (uses H2O again in order to cleave the phosphate off) Glucose 6-phosphatase is also used in the breakdown of glycogen (without this enzyme individuals are hypoglycemic) Regulation of Glycolysis & Gluconeogenesis: There is basically a “balance” going on in the body at all time between glycolysis and gluconeogenesis in order to maintain glucose levels at a specific level (don’t break down too much but don’t generate too much) Le chatlier’s principle (fast speed) shows that influx of glucose will cause it to be broken down and influx of oxaloacetate will cause glucose to be produced There is also allosteric regulation that uses ATP, where ATP will inhibit glycolysis and AMP will inhibit gluconeogenesis In a slow response, you can also react to long term changes through transcriptional regulation (where certain enzymes are made in order to fit the cell’s needs/environment) There is also hormonal regulation (middle speed) through insulin (released with high blood glucose levels, promotes glycolysis because it needs to be broken down) and glucagon (released with low blood glucose levels, promoting gluconeogenesis) which are released whenever the body deviates from the set point of glucose (application of Le chatlier’s principle again When a hormone binds to a receptor on a cell, it causes certain enzymes to be phosphorylated within the cell (inhibiting or activating its use)