12006474
Description
Flashcards by Anna Hogarth, updated more than 1 year ago
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Created by Anna Hogarth
over 6 years ago
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| Question | Answer |
| What are the three different kinds of glucose transporter? | GLUT1 - ubiquitous, low km GLUT2 - Liver and pancreas, high Km, detect high blood glucose GLUT4 - inducible expression in muscle and adipose tissue. Regulated by insulin and AMPK (important in endurance exercise) |
| Which enzymes are responsible for converting glucose to glucose-6-phosphate? Why is this important? | 1) Hexokinase and glucokinase (liver and pancreas only) 2) Glucose transporters are bidirectional, need to stop glucose from leaving the cell |
| How is glucokinase regulated? | By glucokinase regulatory protein (GRP) - when glucose is low GK is bound to GRP in the nucleus, when glucose is high GK is released into the cytoplasm. Allows B cells to detect high blood glucose (GK has a high km, hexokinase is low). Glucokinase activity is also increased by insulin. |
| What are the important steps of glycolysis? (ATP, NADH, reversible by gluconeogenesis) | 1) Glucose ---- Glucose-6-phosphate (hexokinase; ATP-ADP; reversed by glucose-6-phosphatase) 2) Fructose-1-phosphate ---- Fructose-1,6-bisphosphate (PFK1, ATP-ADP; reversed by fructose-1,6-phosphatase) 3) 2X Glyceraldehyde-3-phosphate + PPi --- 1,3-bisphosphoglycerate (glyceraldehyde-3-phosphate dehydrogenase, NAD+---NADH) 4) 2X 1,3-bisphosphoglycerate + ADP ---- 3-phosphoglycerate + ATP (phosphoglycerate kinase) 5) 2X phosphoenolpyruvate + ADP --- pyruvate + ATP (pyruvate kinase, reversed by pyruvate carboxylase complex) |
| What are the net products of glycolysis? | 2 ATP (2 used up in producing glucose-6-phosphate and fructose-1,6-bisphosphate), 2 NAD+, 2 acetyl-Coa |
| What is produced by the TCA cycle? State the steps from which the products come from. | Per 2X pyruvate, 4X CO2 (from isocitrate(6C) to a-ketoglutarate(5C) and a-ketoglutarate(5C) to succinyl-CoA(4C)). 4X NADH (produces by isocitrate and a-ketoglutarate dehydrogenase). 2X FADH (from production of fumarate from succinate). 2XGTP/ATP from succinyl-CoA to succinyl CoA. |
| How many ATP molecules are produced by the ETC? What therefore is the total amount of ATP produced by aerobic glycolysis? What is the other product produced by aerobic glycolysis? | 1) 32 2) 36 (2 from glucose-pyruvate, 2 from TCA) 3) Water |
| What are the four components of the ETC? Which one makes the smallest increase in redox potential? How are ROS produced? Where do cyanide and CO act? | 1) Complex I (NADH-NAD+), II, III (FADH-FAD+) and IV 2) Complex 2 - does not power a proton pump, passes electron to complex III 3) Complex IV needs O2 as final electron acceptor - build up of electrons leads to production of ROS at complexes I and III (near membrane surface) 4) Complex IV |
| Where do fructose, glycerol and substances from the pentose pathway enter glycolysis? | 1) Fructose can be metabolised by hexokinase to produced fructose-6-phosphate. Or by fructokinase in the liver to fructose-1-phosphate then aldolase into triose sugars. 2) Glycerol---glycerol-3-phosphate (glycerol kinase). NAD to NADH produces glucose-1-phosphate. Glucose-1-phosphate to glucose-6-phosphate by phosphoglucomutase. 3) Pentose pathway produces fructose-6-phosphate and glyceraldehyde-3-phosphate |
| What is the function of the pentose pathway? | Provides basis to build hormones and fats. NADP is reduced to NADPH which can used to produce ROS in immune cells. |
| What are the steps in glycogen synthesis? Overall structure of glycogen? | 1) G-G6P (hexokinase) G6P-G1P (phosphoglucose mutase) G1P + UTP - UDP-G1P + PPi (UDP-G-pyrophosphorylase) (then PPi - 2 phosphate) UDP-G1P - glycogen (glycogen synthase) 2) a(1,4) bonds, branching at every 12-14 residues a(1,6) |
| Which enzymes regulate glycogen synthase? | Glycogen synthase is regulated by GLYCOGEN SYNTHASE KINASE (inactivates glycogen synthase through phosphorylation, activated by glucagon). GS is activated by GLYCOGEN/PROTEIN PHOSPHORYLASE (dephosphorylates GS, activated by insulin). |
| What are the steps in glycogenolysis? | GPCR (Gs protein) a subunit activated by binding of glucagon/adrenaline. AC - cAMP - PKA - phosphorylase kinase - glycogen phosphorylase. Glycogen phosphorylase converts glycogen to glycogen (n-1) + glucose-1-phosphate. |
| How is glycogenolysis regulated? | 1) Adrenaline and glucagon activate cascade and inhibit glycogen synthesis (through kinase inhibition) 2) Insulin inhibits through activation of phosphodiesterases (inhibition cAMP) and protein phosphatases (dephosphorylates phosphorylase kinase (a-b) and increases GS activity). Also inhibits GSK3 through PI3K and PKB. 3) Muscle contraction - calcium binds to phosphorylase kinase to increase activity. AMPK (activated by AMP from ATP) increases activity of already active (not phosphorylated) phosphorylase kinase. Pi from conversion can be used to increase activation of phosphorylase kinase. |
| What are the steps of fat (TAG) metabolism? | 1) TAG is broken down into 3X glycerol and fatty acids by hormone sensitive lipase. 2) Glycerol can be entered into glycolysis 3) Fatty acids undergo mitochondrial B oxidation to produce acetyl-CoA and FADH + NADH (fed into the ETC to produce energy). 4) Acetyl-CoA promotes gluconeogenesis and ketogenesis. |
| Other than HSL, what can breakdown triacylglycerol? | Adipose triglyceridelipase |
| What are the steps in the fatty acid to B oxidation (include carnitine shuttle). | 1) FA-Fatty acyl-CoA (Acyl CoA synthase) 2) Facyl-CoA - Facyl-carnitine (CPTI, into intermembrane space). Facyl-carnitine - Facyl-carnitine (M cytosol via translocase). Facyl-carntine - Facyl-CoA (CPT2). B oxidation by acetyl-CoA dehydrogenase. Cycle produces (FA chain length/2) X FADH and NADH and (FA chain length/2) + 1 acetyl-CoA. |
| Where doesn't fatty acid oxidation occur? | Brain - can't cross BBB RBC - no mitochondria |
| What regulates CPT1? | Inhibited by malonyl Co-A (i.e. when fat synthesis occurs, oxidation is inhibited). Glucagon promotes, insulin inhibits (don't need fat oxidation when glucose is high). |
| What can acetyl-CoA from fatty acid breakdown be used for? Why isn't is used in the TCA cycle/aerobic metabolism? | 1) Either for ketogenesis or for gluconeogenesis. 2) Acetyl-CoA inhibits pyruvate decarboxylase (as does raised NADH) and promotes pyruvate carboxylase (gluconeogenesis first step). |
| How are amino acids used for energy? | Can be ketogenic or glucogenic (i.e. feed into either cycle). Feed glutamine-alanine muscle-liver cycle (glutamine to a-ketoglutarate provides substrate for TCA cycle, alanine can be transported to liver, converted to pyruvate which can then be used for gluconeogenesis). |
| What happens in anaerobic respiration? What has to occur to prevent aerobic being attempted? What is the cori cycle? | 1) Pyruvate to lactate (to regenerate NAD+) 2) Build of acetyl-CoA (due to ETC blockage) inactivates PDC preventing pyruvates entry to the TCA cycle 3) Lactate transported to liver, converted back to pyruvate - gluconeogenesis. |
| What are the three enzymes involved in converting pyruvate to phosphoenolpyruvate in gluconeogenesis? | 1) Pyruvate decarboxylase 2) Malate dehydrogenase X2 3) Phosphoenolpyruvate carboxykinase |
| What happens to metabolism in the fed state (high BG)? | Insulin secretion - inhibits glycogenolysis through phosphodiesterase (cAMP inhibition) and protein phosphatase. Increases glycolysis (reduces gluconeogenesis) through increased hexokinase and F2,6P2 activity. Promotes glycogen synthesis (activates GS through protein phosphatase activity and inhibits GSK via PI3K and PKB). Increased fat synthesis as excess citrate leaves mitochondria, broken down into oxaloacetate and acetyl-CoA. Malonyl-CoA + insulin inhibit fatty acid oxidation (via CPT1 inhibition). Increased GLUT4 expression. High BG also promotes pyruvate decarboxylase activity. Excess citrate inhibits PFK1. High fructose-6-phosphate increase PFK1 activity. |
| What happens during low blood sugar (glucagon)? | Glucagon inhibits glycolysis through inhibition of F26P2. Low BG inhibits pyruvate decarboxylase. Inhibition of glycogen synthesis through activation of GSK/PKA. Increased glycogenolysis via GPCR (Gsa). Increased gluconeogenesis - cAMP increases FOXO expression which increases G-6-phosphatase expression (last step of gluconeogenesis). Glucagon promotes fatty acid entry to carnitine shuttle through CPT1. |
| What happens during starvation? | Proteolysis (produces pyruvate and products which can be used in the TCA cycle) and lipolysis. Ketogenesis for energy. PPARa is increased, transcription factor which increases the amount of HMG-CoA synthase. CPT1 expression is also increased in periods of prolonged starvation. |
| What are the steps in ketogenesis? | 3 acetyl-CoA are converted into HMG-CoA (3-hydroxy-3-methylglutaryl-coA; 6 carbons) by HMG-CoA synthase. This is then converted into acetoacetate by HMG-CoA reductase. Acetoacetate is split into acetone and B-hydroxybutyrate by B-hydroxybutyrate dehydrogenase. Acetone and B-hydroxybutyrate are in equilibrium, the amount of either is dependent on the ratio of NAD+/NADH. |
| How is ketogenesis regulated? | By PPARa. Enzymes: HMG-CoA synthase, HMG-CoA lyase and ratio of NADH to NAD+. NADH to NAD+ to convert acetone to B-hydroxybutyrate. Insulin decreases ketogenesis. |
| Why do ketogenesis and gluconeogenesis increase in diabetes? (why can diabetics who aren't consuming glucose become hyperglycaemic?) | 1) Ketogenesis occurs because insulin usually inhibits ketogenesis. 2) Gluconeogenesis occurs because there are more 'building blocks' (amino acids and fatty acids) available as tissues aren't taking up glucose. Insulin also usually inhibits gluconeogenesis through promotion of glycolysis (glucokinase and F26P2). The glucagon/insulin ratio is therefore increased resulting in hyperglycaemia. |
| What are the two different types of muscle fibre? | Fast twitch - anaerobic. Heavy chain myosin type II, fast ATPase. 2a - anaerobic only. 2b - anaerobic and aerobic (mixed endurance). Low myoglobin and mitochondria. Slow twitch - aerobic. High myoglobin and mitochondria. Oxidative respiration. |
| What happens to respiration short term exercise? | Fast twitch muscle fibres dominate - anaerobic metabolism. Lack of oxygen blocks the ETC, build of acetyl-CoA promotes pyruvate to lactate (pyruvate carboxylase, thiamine phosphopyruvate is the cofactor) and inhibits pyruvate decarboxylase (TCA cycle). Lactate dehydrogenase converts into lactate. Enters cori cycle, provides glucose for muscle energy (no net production of glucose and liver is using energy). Liver glycogen is not mobilised, muscle glycogen is. Note that a decrease in pH will decrease glycolysis. |
| How do calcium, AMP and AMPK regulate short term exercise? | CALCIUM : WITH O2: increase isocitrate and a-ketoglutarate activity and activates pyruvate decarboxylase phosphatase activity (increases pyruvate to acetyl-CoA) PROMOTES TCA CYCLE. Activates phosphorylase kinase (promotes GLYCOGENOLYSIS, doesn't need O2) AMP: Increases GLUT4, increases activity (of already active) phosphorylase kinase). AMP stimulates PFK1 (inhibits ATP) Activated AMPK inhibits acetyl-CoA carboxylase which reduces production of malonyl CoA, disinhibits fatty acid entry into the carnitine shuttle. |
| How is pyruvate decarboxylase regulated? | Through PDH kinase and PDH phosphatase. PDH phosphatase is activated by calcium - dephosphorylation activates PDH. Acetyl-CoA inhibits PDH. |
| What happens during endurance exercise? | AMPK - inhibits acetyl-CoA carboxylase, reduces production of malonyl-CoA. This disinhibits CPT1 and promotes fatty acid entry into the carnitine shuttle. In the heart activation of PFK2 increases PKF1 activity (via F26P2). Aerobic glycolysis is promoted in slow twitch muscle fibres. Fatty acid breakdown is also promoted, this may inhibit the TCA cycle and promote gluconeogenesis due to the build up of acetyl-CoA. |
| Why do athletes carb load and increase vitamin B intake before endurance exercise? | Carbohydrate loading increases blood glucose, increasing glycogen stores. B vitamins are used as cofactors in various stages of the TCA cycle - B1 is part of thiamine phosphopyruvate. |
| What happens during hypoxia? | Low pH (lactate) inhibits glycolysis. 1) Switch off non-vital functions 2) Promote anaerobic metabolism 3) Protect against ROS HIF1a (transcirption factor) subunit is stabilised and therefore expression increases. It binds to the hypoxia response element (HRE) leading to increased VEGF and EPO. But in terms of metabolism it promotes anaerobic glycolysis and reduces ROS through increased expression of PGC1a which cause mitochondrial autophagy. Promotes PFK1 activity. |
| In fatty acid synthesis how is acetyl-CoA carboxylase regulated? (Fatty acid synthesis) | 1) Polymerisation - polymer is the active form 2) Citrate promotes activity, long chain fatty acids inhibit (palmityl-CoA) 3) AMPK - inhibits acetyl-CoA, i.e when energy is low fatty acid synthesis won't occur. |
| Why do immune cells need products of amino acid break down (TCA top ups)? Products of the pentose phosphate pathway? | Immune cells use substances in the TCA cycle (such as a-ketoglutarate) to produce haem which is needed for catalase reactions. Glutamate can be converted to a-ketoglutarate through transamination which |
| What is unique about cancer cell metabolism? What do cancer cells need from amino acids? | 1) Cancer cells undergo anaerobic metabolism even when oxygen is available. Rate of glycolysis increases 200X in cancer cells. Warburg effect. Hypoxic conditions in areas of the tumour promote PFK2 activity which increases F26P2 activity, increasing PFK1 activity and therefore rate of glycolysis. HIF1a induced which also increases glycolysis. 2) TCA cycle topped up by glutamate and glutamine as cancer cells are using huge amounts of energy for growth. |
| What are the steps of alcohol metabolism? How does fatty liver occur? | Ethanol is converted into acetaldehyde (alcohol dehydrogenase). Acetaldehyde + NAD+ -- Acetate + NADH (Acetaldehyde dehydrogenase) ATP + Acetate + CoA -- AMP + Pi + Acetyl-CoA. Acetaldehyde is a carcinogen and known toxin. Some people lack the enzyme to break it down completely (asian flush). Fatty liver occurs because the build of acetyl-CoA causes a switch to fatty acid synthesis and impairs the entry of pyruvate to TCA cycle. |
| What is disulfiram (antabuse)? | Inhibits acetaldehyde dehydrogenase, gives instant sensation of hangover and is used to try and help alcoholics. |
| Consider how the following are regulated: PDC? PC? Glycogen synthase? Hexokinase? PFK1? Acetyl-CoA carboxylase? CPT1? | X |
| What effect on metabolism do the following have? Ca2+? (3) AMPK? (2) AMP? Glucagon? Insulin? | 1) Increases entry to TCA cycle through activation of PDC PHOSPHATASE. Isocitrate and a-ketoglutarate activity. Increases GLYCOGENOLYSIS through phosphorylase kinase activation. 2) AMPK inhibits acetyl-coA carboxylase (increases fatty acid oxidation through decrease malonyl-CoA. Increases PFK2 activity in heart 3) Increases GLUT4 expression, activates AMPK (PFK2), increase PFK1 activity (relieves inhibition by ATP), stimulates phosphorylase kinase. |
| What four things cause muscle fatigue? | 1) 500g glucose stored - marathon requires 700g, longer term fatty acid oxidation allows a power output of 60% (i.e. less than acetyl CoA) 2) Depletion of phosphocreatine 3) Excessive rates of conversion of glycogen & glucose to lactose acid - decreases pH and inhibits glycolysis and oxidative phosphorylation. 4) Insufficient (aging), inflexible (obesity) or inefficient mitchondria (density increases with regular exercise). |
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