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127 Cards in this Set
- Front
- Back
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2 main sites of metabolism:
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-Mitochondria
-Cytoplasm |
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What 3 metabolic pathways are limited to MITOCHONDRIA?
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-FA B-oxidation
-AcCoA production -Krebs cycle |
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What 5 metabolic processes occur in the CYTOPLASM?
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-Glycolysis
-FA SYNTHESIS -HMP shunt -Protein synthesis (rER) -Steroid synthesis (SER) |
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What 3 metabolic pathways take place in BOTH the mitochondria AND cytoplasm?
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-Heme synthesis
-Urea cycle -Gluconeogenesis |
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What is ATP made up of?
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-Adenine
-Ribose -3 phosphates |
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How many ATP are produced from Aerobic metabolism of one glucose molecule? Via which shuttle?
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38 via the Malate shuttle
36 via the G3P shuttle |
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How many net ATP are produced by ANAEROBIC metabolism of one glucose molecule?
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Only 2!!
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What is ATP used for?
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Hydrolysis and release of energy coupled to energetically unfavorable reactions.
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What is the activated carrier of phosphoryl?
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ATP
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What are three activated carriers of electrons?
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-NADH
-NADPH -FADH2 |
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What are 2 activated carriers of Acyl?
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Coenzyme A
Lipoamide |
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What is the activated carrier of CO2?
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Biotin
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What is the activated carrier of 1-carbon units?
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THF - tetrahydrofolate
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What is the activated carrier of methyl groups?
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SAM - s-adenosyl methionine
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What is the activated carrier of Aldehydes?
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TPP
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What IS SAM?
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The methyl donor man
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What is SAM made up of?
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ATP + Methionine
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What does SAM do?
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SAM transfers methyl units!
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What is regeneration of methionine, and hence SAM, dependent on?
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Vitamin B12
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What are the universal electron acceptors?
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NAD, FAD, and NADP
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What are NAD and NADP?
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Nicotinamides
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What is FAD?
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Flavin nucleotide
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Where is NADPH produced?
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HMP shunt
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What is NAD+ used in?
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CATABOLIC PROCESSES - carries reducing equivalents away as NADH
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What is NADPH's general use?
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ANABOLIC processes as a SUPPLY of reducing equivalents
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What 3 process is NADPH used in?
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-Anabolic processes
-Respiratory burst -P450 enzyme reactions |
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What are the 2 main anabolic processes that use NADPH?
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-Steroid production
-Fatty acid synthesis |
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Where is the Oxygen dependent Respiratory Burst seen?
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In neutrophils' phagolysosomes
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What are the 6 enzymes employed by the Respiratory burst?
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1. NADPH oxidase
2. Superoxide dismutase 3. Myeloperoxidase 4. Catalase/peroxidase 5. Glutathione reductase 6. G6PD dehydrogenase |
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What does NADPH oxidase do?
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Oxidizes NADPH as it reduces Oxygen into Superoxide radicals
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What happens to the Superoxide?
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Superoxide dismutase turns it into Peroxide H2O2
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What happens to Peroxide?
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Cl gets added to it by Myeloperoxidase to make BLEACH
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What does the Bleach (HOCl) do?
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Kills bacteria in the phagolysosome
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What happens to Peroxide that is not converted to bleach?
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It gets into the cytosol where it is converted to WATER by GSH peroxidase and by catalase.
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What happens to GSH peroxidase in the process of converting H2O2 to H2O?
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GSH becomes GSSG
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What is necessary to regenerate GSH from GSSG?
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Glutathione reductase and NADPH
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What is the source of NADPH?
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HMP shunt
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What is necessary for regenerating NADPH from NADP+ which is produced by GSSG reductase?
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Glucose-6P and G6PDehydrogenase
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What is the 1st thing that happens when cells take up glucose?
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Phosphorylation
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What enzyme phosphorylates glucose at ubiquitous sites?
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Hexokinase
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What enzyme phosphorylates glucose in the liver?
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Glucokinase
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What is the affinity/capacity of
-hexokinase -glucokinase |
Hexokinase: High affinity/Low capacity
Glucokinase: Low affinity/High capacity |
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So what is the Km for glucose of
-hexokinase -glucokinase |
Hexo = low Km
Gluco = high Km |
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How are Hexokinase and Glucokinase regulated?
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Hexo: by neg feedback inhibition
Gluco: not inhibited |
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Why is it good that Glucokinase has low affinity but does not exhibit neg FB inhibition?
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The liver only takes up glucose in the FED state when glucose is in excess; but there is not capacity.
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So what is the 1st step in glycolysis?
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D-glucose is phosphorylated to Glu-6P by hexo/glucokinase
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What inhibits this first step?
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G6P
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What is the next important step in Glycolysis?
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The RATE LIMITING STEP!!!
Phosphofructokinase-1 converts G6P to Fructose 1,6-BP |
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What inhibits/stimulates PFK1?
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Inhib: ATP and Citrate
Stim: AMP/F2,6-BP |
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What is the next important step in Glycolysis?
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PEP -> Pyruvate by Pyruvate kinase
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What is Pyruvate kinase inhibited by? Stimulated?
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Inhib: ATP and Alanine
Stim: F1,6-BP |
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What happens to Pyruvate?
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Pyruvate Dehydrogenase converts it to AcCoA
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What inhibits PDH?
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ATP, NADH, and AcCoA
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So what is the MOST POTENT ACTIVATOR of Phosphofructokinase-1? Which step is this again?
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F26BP! This is the RLS of glycolysis
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How potent of an activator IS F26BP?
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It even overides the inhibiting effects of ATP and Citrate
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What enzyme MAKES F26BP?
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Fructose Bisphosphatase 2
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When is Fructose Bisphosphatase 2 active? Why?
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In the fasting state - to produce F26BP, TO ACTIVATE PFK1!!
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What is PFK2's action?
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Breaks DOWN F26BP into F6P
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When is PFK2 active?
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In the FED state
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So what is the most potent activator of PFK1 and when is it elevated then?
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F26BP - high in the fasting state when Fructose Bisphosphatase 2 is active
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What are Glycolytic enzyme deficiencies associated with?
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HEMOLYTIC ANEMIAS
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Why are glycolytic enzyme deficiencies associated with HA's?
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Because RBCs are utterly dependent on glucose for their survival
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HOW do RBCs use Glucose?
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ANAEROBICALLY - they have NO MITOCHONDRIA for aerobic metabolism.
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So what are RBCs solely dependent on for their energy?
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Glycolysis
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What are the top 2 most common glycolytic enzyme deficiencies?
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-Pyruvate Kinase 95%
-Glucose 6phosphate dehydrog? 4% |
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What is the Pyruvate dehydrogenase complex made up of?
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3 enzymes requiring 5 cofactors
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What are the 5 cofactors of the PDH complex?
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-First four B vitamins
-Lipoic acid |
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What are the B vitamins that are cofactors for PDH complex?
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-Thiamine Pyrophosphate -B1 TPP
-FAD - B2, Riboflavin -NAD - B3, Niacin -CoA - B5, Pantothenate -Lipoic acid |
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What other enzyme complex is very similar to PDH?
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alpha-Ketoglutarate dehydrogenase - same cofactors, similar substrates
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What inhibits LIPOIC ACID?
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Arsenic!
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What does Arsenic inhibition of Lipoic Acid do?
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MAKES YOU GO TO YOUR GRAV
-Garlic breath -Ricewater stools -Vomiting (Arsenic) |
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What is the reaction catalyzed by PDH complex?
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NAD + CoA + Pyruvate goes to AcCoA + NADH + CO2
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What is the PDH complex reaction activated by?
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Exercise
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What substrates activate PDH complex?
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-NAD+/NADH ratio elevation
-ADP -Calcium |
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What happens if the PDH complex enzyme is deficient?
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Pyruvate and Alanine build up and cause lactic acidosis
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What are 2 ways that PDH deficiency can occur?
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-Congenital defect
-Alcoholics - lack Vit B1 |
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What are the clinical findings when PDH complex is deficient?
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Neurologic deficits
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What is the treatment for PDH complex deficiency?
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Increased intake of FAT or KETOGENIC substrates - Lysine and Leucine
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Why Lys/Leu?
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These are the only purely ketogenic amino acids!
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Once PYRUVATE is made, what are 4 fates of what it can become? What enzyme does each thing?
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-Alanine (ALT)
-Oxaloacetate (P Carboxylase) -AcCoA (PDH) -Lactate (LDH) |
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How many ATP equivalents are required for generating GLUCOSE FROM Pyruvate?
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6 ATP!
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What is the main role of Alanine generated by ALT conversion of Pyruvate?
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To take Amine groups from MUSCLE to LIVER
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What are the 2 main functions of OOA?
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-Replenish the TCA cycle
-Gluconeogenesis |
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What will Pyruvate conversion to AcCoA contribute to?
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The TCA cycle and ETC!
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What is Lactate?
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The endproduct of anaerobic metabolism
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In what 6 sites is Anaerobic metabolism the MAIN pathway of glycolysis and energy production?
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-Lens
-Cornea -Testes -Renal medulla -RBCs/WBCs |
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What is the Cori Cycle?
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Transfer of Lactate from Muscle/RBCs to the liver
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What does the LIVER do with the lactate?
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Converts it back to pyruvate and glucose - gluconeogenesis
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Why do Muscle/RBCs need the Cori cycle?
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To get rid of the reducing equivalents (Lactate) and shift that metabolic burden to the liver, which allows Muscle/RBCs to function anaerobically
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And what is the NET ATP production of Anaerobic glycolysis?
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2ATP
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Where does the TCA cycle occur?
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In mitochondria
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What are the 8 substrates in the TCA? Acronym?
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Can I keep selling sex for money officer?
Citrate, Isocitrate, a-KG, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate |
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What feeds the TCA?
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Pyruvate from the PDH complex reaction
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And what inhibits PDH complex again?
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ATP, NADH, and AcCoA
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What makes Citrate? What inhibits it?
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Citrate synthase
-inhib by ATP |
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How much NADH is made by the TCA? At what reactions?
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3 NADH
-Isocitrate dehydrogenase -a-KG dehydrogenase -Malate dehydrogenase |
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What other electron carrier is reduced in the TCA? What reaction?
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FAD makes FADH2
Succinate dehydrogenase making succinate -> fumarate |
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How many CO2 produced in the TCA and at what reactions?
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2 CO2
-a-KG dehydrogenase -Succinyl CoA synthase |
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What ELSE does the Succinyl CoA synthase reaction make?
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GTP!
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So what is the net production from the TCA cycle per 1 AcCoA?
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-3NADH
-1FADH2 -2CO2 -1GTP |
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And how many ATP are then made per AcCoA? Where?
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12 - by the ETC
3 ATP per NADH x 3 = 9 2 ATP per FADH2 x 1 = 2 plus the GTP |
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What is important to remember about a-KG dehydrogenase?
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-Same cofactors as PDH complex
-Substrate is a-ketoglutarate |
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Where does the ETC and Oxidative phosphorylation take place?
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MITOCHONDRIA
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What does the ETC consist of? where?
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Complex 1, 3, 4, and 5
On the inner mitochondrial membrane |
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What happens as electrons pass through the ETC?
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Protons get pumped into the intermembranous space, setting up a PROTON MOTIVE FORCE
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Where does NADH get reduced?
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Complex I
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Where do electrons flow from complex I to?
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Coenzyme Q in the membrane
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Where does FADH2 get reduced?
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Complex II - CoQ
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Where do electrons flow from CoQ?
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To Complex III, then cytochrome C
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What happens at Complex IV?
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1/2 O2 gets converted to H2O
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What is Complex V?
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ATP synthase
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What happens at Complex V?
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ADP + Pi -> ATP + H2O on the mitochondrial MATRIX surface as protons flow into the matrix from the intermembranous space
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How many ATP are made
-per NADH -per FADH2 |
NADH = 3 ATP
FADH2 = 2 ATP |
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What are 3 types of oxidative phosphorylation poisons?
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-ETC inhibitors
-ATP synthase inhibitors -Uncoupling agents |
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What are 4 ETC inhibitors?
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-Rotenone
-Cyanide -Antimycin A -Carbon monoxide CO |
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What effect will inhibition of the ETC have?
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Decreased PMF, blocks ATP synthesis
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What is an ATPase inhibitor?
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Oligomycin
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What effect will ATPase inhibition have?
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Blocks ATP synthesis, but INCREASES the PMF
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Will ATP be produced in the presence of Oligomycin?
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No - it stops up the ETC and stops electron flow.
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What are 3 uncoupling agents?
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UCP
2,4-dinitrophenol Aspirin |
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What is the mechanism of uncoupling agents?
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Decreased membrane permeability decreases the proton gradient and oxygen consumption.
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What effect do uncoupling agents have on
-ATP production -ETC flow |
ATP synthesis stops
ETC continues |
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So what is the main effect uncoupling agents have?
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Blow off a lot of steam
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So what are the ETC INHIBITORS:
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CCAR
-Cyanide -CO -Antimycin A -Rotenone |
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And what is the ATP synthase inhibitor?
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Oligomycin
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And what are the 3 uncoupling agents?
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2,4-dinitrophenol
Aspirin UCP |
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What are the 4 irreversible enzymes in GLUCONEOGENESIS?
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1. Pyruvate carboxylase
2. PEP carboxykinase 3. F16-bisphosphatase 4. Glucose6phosphatase |
