Biochemistry

• A Catabolic pathway is breaking down fuel molecules to generate energy

  An Anabolic pathway is using energy to build complex biomolecules required for life
• Glycolysis, pentose phosphate pathway, fatty acid synthesis all happen in the cytosol
• Aldehyde is an organic molecule with a carbonyl group at end of C chain

  Ketone is an organic molecule with carbonyl group in middle of C chain
• almost all sugars are in D-isomer form
• Starch stores glucose in plants and has 2 types: unbranched (amylose) + branched (amylopectin)
• Glycogen stores glucose in animals, is more branched than starch,

  formed around a protein in core known as glycogenin 
• Cellulose forms plant cell walls and is most abundant biomolecule with a rigid formation
• Chitin is a component of the extoskeleton of insects + crustaceans

  composed of N-acetylglucosamine groups
• The ∆G for glycolysis is -96.2 kJ/mol, meaning it is energetically favorable
• When energy levels are high: lots of ATP + glycolysis is inhibited

  When energy levels are low: lots of ADP and AMP + glycolysis is stimulated 
• 3 irreversible steps of glycolysis are the main control points (large negative ∆G)

  o   First step: catalyzed by hexokinase

  o   Third step: catalyzed by phosphofructokinase + main site of regulation

  o   Last step: catalyzed by pyruvate kinase 
• High ATP will inhibit PFK enzyme and cause intermediates from earlier to build up (more fructose-6P + glucose-6P). Glucose 6P inhibits hexokinase and forms negative feedback loop. Glucose 6P is stored in muscles as glycogen instead.
• In anaerobic conditions, NADH is oxidised to NAD+ to re-enter glycolysis. The e- are passed to pyruvate, converting it to lactate.
• In aerobic conditions, pyruvate and NADH are passed into the mitochondrion to enter the TCA cycle.
• Fructose enters glycolysis and then into the liver through being converted to DHAP + GAP. GAP needs to be further converted to glyceraldehyde 3-P.
• Galactose must be converted to glucose 1-P with the help of UDP-glucose. It must then be further converted to glucose 6-P
• Gluconeogenesis involved making glucose from non-carbohydrate molecules such as: lactate, amino acids, glycerol. Lactate can be converted to pyruvate, amino acids can be converted to pyruvate or oxaloacetate, glycerol can be converted to dihydroxyacetone phosphate 
• Gluconeogenesis' first step is irreversible: pyruvate to phosphoenolpyruvate. Unlike glycolysis, requires 2 enzymes to convert this, producing oxaloacetate as an intermediate. Oxaloacetate is taken out of the mitochondrion by the malate shuttle.
• The second irreversible step in gluconeogenesis is Fructose 1,6-BP to fructose 6-P done by FPBase. The mirror reaction in glycolysis is done by the PFK enzyme. These two enzymes are on the same polypeptide and are regulated by fructose 2,6-BP.
• Fructose 2,6-BP is a signal of high glucose, therefore inhibiting fructose 1,6-BP so that no more glucose is formed.
• When glucose is scarce, glucagon is released which activates protein kinase A which phosphorylates the polypeptide. This activates FBPase and inhibits PFK. This means gluconeogenesis is on
• When glucose is high, insulin is released which activates phosphoprotein phosphatase. This removes the phosphorylation on the polypeptide which stimulates PFK and inhibits FBPase. This means that glycolysis is on.
• The last step in gluconeogenesis is irreversible: Glucose-6P to glucose. Glucose is then released in the liver. The reaction only takes place in the ER, so glucose-6P is transported to the ER by T1. Then after the reaction, glucose and phosphate are transported by T2 and T3 respectively out of the ER.
• The Cori Cycle is where lactate (produced in anaerobic glycolysis) is transported to the liver and converted to pyruvate and then glucose by gluconeogenesis. It is very important for buffering glucose levels and keeps muscles going, even without oxygen.
• The Pentose Phosphate Pathway uses glucose-6P as its starting point and produces 2 products: NADPH (great reducing power) and ribose-5P (basis of nucleic acid synthesis).
• PPP happens in 2 stages. The first stage is oxidative and irreversible, producing 2 NADPH and 1 pentose. The second is stage is non-oxidative and reversible, turning the pentose into trioses or hexoses. This is a requirement for it to enter either glycolysis or gluconeogenesis.
• One of the first enzymes used in PPP is glucose 6P dehydrogenase, and is a common deficiency which causes favism. This reduces the amount of NADPH produced which is required to make glutathione. Glutathione is required to detoxify molecules in blood. This causes oxidative damage to RBC's which leads to haemolytic anemia
• When Pentose > NADPH, glycolysis is switched on which makes fructose 6P and glyceraldehyde 3P. Then non-oxidative PPP is switched on in reverse to form pentose.
• When Pentose = NADPH, only the oxidative phase is switched on
• When Pentose < NADPH, oxidative phase is switched on to generate lots of NADPH and pentose, and then non-oxidative shunts pentose into glyceraldehyde 3P which is used in gluconeogenesis. This forms more glucose 6-P which can repeat the cycle.
• When NADPH + ATP are needed, oxidative PPP makes lots of NADPH and pentose. Pentose is then shunted into non-oxidative phase to glyceraldehyde 3P which is then fed into glycolysis to form pyruvate and ATP.
• Glycogen synthesis is done by glycogen synthase. UDP glucose is the substrate for glycogen synthase. UDP glucose is made from phosphoglucomutase turning glucose 6P into glucose 1P and then adding UDP. To make the branched part of the chain, a branching enzyme is needed. Glycogen synthase must start from a primer called glygogenin.
• Glycogen breakdown is also known as glycogenolysis and is done by glycogen phosphorylase. The enzyme phosphorylates the end of the chain which breaks the bond and releases glucose 1P. Phosphoglucomutase then turns glucose 1P into glucose 6P which can go into glycolysis. Transferase is needed to breakdown branches. The more branched a chain is, the faster the breakdown.
• High glucose and ATP 6P actives glycogen synthase and inhibits glycogen phosphorylase. Ca2+ activates glycogen phosphorylase (signal for contracting muscles) and inhibits glycogen synthase. Insulin (sign of high glucose) also activates glycogen synthase.
• The first step in the TCA cycle is transporting and converting pyruvate into acetyl CoA, which is done by the pyruvate dehydrogenase complex (PDC) in the mitochondrion.
• The PDC is made up of 3 enzymes: E1 (uses TPP to decarboxylate + oxidise pyruvate), E2 (uses lipoamide to transfer resulting acetyl group to CoA), E3 (uses FAD to reset the complex back to its original form)
• Amino acids cannot be stored or excreted, so it must be degraded in the liver. The nitrogen is excreted as urea in mammals in their urine. The rest of the molecule is converted into intermediates for fat metabolism.
• The first step of nitrogen excretion produces NH4+. This occurs in the mitochondrial matrix to keep the toxicity out of the cytosol. In this step, aminotransferases catalyse the transfer between amino and keto acids. They use the cofactor PLP to transfer the amino group, the aldehyde forming a Schiff-base linkage.
• The second step of nitrogen excretion utilises the urea cycle. The urea cycle is very energetically demanding, and uses the equivalent of 4 ATP. The urea cycle has some intermediates which link to TCA, such as fumarate (oxidised to malate + converted to oxaloacetate).
• Most amino acids are gluco genic, meaning their carbon skeletons can be converted into intermediates of the TCA cycle or other molecules involved in gluconeogenesis. Some amino acids are ketogenic, and they provide acetyl CoA for the TCA cycle. The only 2 ketogenic amino acids are: Leucine, Lysine.