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498 Cards in this Set
- Front
- Back
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Three enzymes in the pyruvate dehydrogenase complex?
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Pyruvate dehydrogenase
Dihydrolipoyl transacetalyase Dihydrolipoyl dehydrogenase |
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Lipoic acid is also known as?
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Lipoamide
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TPP=?
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Thiamine pyrophosphate
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FMN=?
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Flavin monoucleotide
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FAD=?
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Flavin adenine dinucleotide
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Riboflavin=?
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ring + ribitol
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What is the reduced form of FAD and what happens to reduce it?
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FADH and occurs by transferring 2H atoms along with 2e- or 2H
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PDH Reaction 1
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Pyruvate onto TPP
-goes to hydroxyethyl-TPP -removes CO2 |
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PDH Reaction 2
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Hydroxyl-TPP + lipoamide-E2 goes to acetyl-lipoamide-E2 +TPP
-a disulfide is oxidized -acetyl-lipoamide-E2 is reduced |
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Reaction 3 for PDH
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E2 transfers acetyl to CoA-acetyl-Coa leaves
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PDH Reaction 4
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E3(Dihydrolipoyl dehydrogenase) uses its coenzyme FAD to oxidize lipoamide back to disulfide to produce FADH2
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PDH Reaction 5
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FAD is recovered from FADH2 by reducing NAD to NADH
-NADH generated |
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Regulation of Pyruvate Dehydrogenase
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-Allosteric inhibition by Acetyl-Coa and NADH
-Ihibiation by high ATP -Allosteric activation by AMP |
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Pyrivate Dehydrogenas activation/deactivation
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-Phosphatase activates E1-> activated by insulin
-Kinase deactivates E1->activated by acetyl-CoA, NADH, and not cAMP inhibitors:pyruvate, and ADP |
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How is phosphatase regulated?
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Insulin (indirectly)
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How is kinaseactivated?
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Acetyl-CoA, NADH, and cAMP
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How is kinase deactivated
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Pyruvate, ADP
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TCA Cycle
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Acetate from acetyl-CoA is derived from pyruvate and other metabolites and is oxidized to CO2
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What is produced for each cycle of TCA
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GTP
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What does the TCA cycle provide ?
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Reduced electron carries in the form Three NADH and one FADH2 and then energy for oxidative phosphorylation
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Other products of TCA cycle
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Precursors for anabolic processes
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Where are all enzymes for the TCA cycle at?
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Mitochrondrial matrix or inner mitochondrial membrane
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Overall reaction for the TCA cycle
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Acetyl-Coa+ 3NAD+ + FAD+ GDP + Pi + 2 H2O->2CO2 + 3NADH+FADH2+GTP+2H++CoA
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Step 1 TCA
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Acetyl-CoA + oxaloacetate
-Producres Citrate -Enzyme: citrate synthase -Uses h2O -Committing step of TCA -Highly exergonic |
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Step 1 enzyme
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Citrate synthase which is a condensing enzyme
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What is the committing step of the TCA cycle?
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Step 1
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Step 2 of the TCA
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Citrate to isocitrate with an intermediate of cis-aconitate
-Enzyme:aconitase -aconitate never leaves enzyme -dehydration/hydration |
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Step 2 enzyme
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Aconitase
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Step 3 TCA
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Oxidation of isocitrate to a-ketoglutarate
-Enzme: isocitrate dehydrogenase -Produces NADH -Two isoforms of isocitrate: one uses NAD+ or NADP+ -First oxidation in TCA -Loss of CO2 |
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Step 3 enzyme
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isocitrate dehydrogenase
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What are the two forms of isocitrate dehydrogenase?
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one uses NAD+ and NADP+
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Step 4 TCA
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a-ketoglutarate to succinyl-CoA and CO2
-Enzyme: a-ketoglutarate dehydrogenase complex -Produces NADH -Produces CO2 -Second Oxidation -Highly Exergonic (-33.5) -Similar to pyruvate to acetyl CoA but no regulation |
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Step 4 Enzyme
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a-ketoglutarate dehydrogenase complex
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Step 5 TCA cycle
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Succinyl CoA to succinate
-Enzyme: Succinyl CoA Synthase -Uses substrate level phosphorylation -Produces GTP -Near equilibrium |
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Step 5 enzyme
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succinyl CoA synthase
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Step 6 TCA
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Oxidation of succinate to fumarate
-Enzyme: succinate dehydrogenase -A dehydrogenation -Produces a double bond in fumarate -Produces FADH2 -Third oxidation in TCA -Electrons captured here for ETS |
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Step 6 enzyme
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Succinate Dehydrogenase
-a flavin containing enzyme that is BOUND to the inner membrane of the mitochrondria |
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Where are electrons captured for the ETS?
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Step 6 of TCA (succinate to fumarate)
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FADH2 yields how many ATP?
NADH oxidation yields how many ATP? |
2
3 |
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Step 7 TCA
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Hydration of fumarate to I-malate
-Enzyme: fumarase -Malate is used in gluconeogensis |
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Step 7 Enzyme
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Fumarase
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Step 8 TCA
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Malate to Oxaloacetate
-Final step of cycle Enzyme: malate dehydrogenase -Produces NADH -Fourth oxidation -Same step in gluconeogenisis |
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Step 8 enzyme
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Malate dehydrogenase
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Glycolysis energy yield?
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Glucose-> 2 pyruvate + 2NADH + 2 ATP
-8 ATP |
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Pyruvate Dehydrogenase energy yield?
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2 pyruvate-> 2 acetyl coa + 2 NADH
-6 ATP |
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TCA Cycle energy yield
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acetyl Coa-> 2 CO2 + 3 NADH _ FADH2 + GTP
-2x12 ATP |
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Overall evergy yield from glucose
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38 ATP
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delta G for the oxidation of glucose to CO2
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2,480 kJ/mole
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Percent conversion of energy in CO2 to ATP
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41% (1,160 kJ/mol)
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Way Citric Acid Cycle is regulated?
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1) Pyruvate dehydrogenase
2)Citrate Synthase 3) Isocitrate Dehydrogenase 4)a-Ketoglutarate dehydrogenase |
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Pyruvate dehydrogenase and its role in TCA regulation
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inhibited by ATP, acetyl CoA and NADH
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Citrate Synthase and its role in TCA regulation
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It's substrate is oxaloacetate which is limited
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Isocitrate Dehydrogenase and its role in TCA regulation
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activated by ADp and inhibited by NADH
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a-Ketoglutarate dehydrogenase and its role in TCA regulation
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ihibited by succinyl-CoA and NADH
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What is the major regulator for TCA?
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the intramitochondrial NAD+/NADH ratio
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High oxygen results in a ___ NAD+/NADH ratio
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increased level (decreased for low oxygen)
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What is a measure for oxygen availability?
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NAD+/NADH ratio
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Amphibolic=?
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removal of intermediates
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Anaplerotic=?
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filling reactions that replace cyclic intermediates
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Amphibolic pathways
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remove intermediates to make amino acids
ex: fatty acid biosynthesis and heme biosynthesis |
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Anaplerotic Reactions
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-Pyruvate carboxylase replase oxaloacetate (most important in kidney and liver)
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What is the most important anaplerotic reaction
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Pyruvate carboxylase which produces oxaloacetate (used in gluconeogensis too)
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Where is the pyruvate carboxylase reaction most important?
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Kidney and Liver
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Pentose Phosphate Shunt
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Oxidizes glucose to produce NADH and ribose 5-phosphate which are required for biosynthesis
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What is required for biosynthesis?
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NADPH and ribose 5-phosphate
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What oxidizes the substrates in PPS?
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NAD+/NADH
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What reduces substrates in PPS?
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NADP+/NADPH
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What are the functions of PPS?
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1) Generate reducing power in the cytosol as NADPH
2) generate pentose phosphates 3)Generate aldose and ketose families of C3,C4, C5 and C7 carbs 4) Pathway to produce glucose from CO2 in plants |
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Where is PPS located?
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Cytosol
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How many phases are there in PPS?
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Two phases one oxidizing and and one non-oxidinzg
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Oxidative phase of PPS Step 1
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G6P->6-phosphogluconolactone
-Produces NADPH -Enzyme: G6P Dehydrogenase |
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Enzyme for oxidative phase of PPS
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G6P Dehydrogenase
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Oxidative phase of PPS Step 2
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6-phosphogluconolactone to 6-phosphogluconate (sugar acid)
-Enzyme: Lactonase |
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Enzyme for Step 2 oxidative phase of PPS
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Lactonase
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Oxidative phase of PPS Step 3
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6-Phosphogluconate to 5CKetose
-Ennzyme: 6-phosogluconate dehydrogenase -Undergoes oxidative decarboxylation at C1 -Produces NADPH |
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Oxidative phase of PPS Step 4
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-Isomeization of 5C Ketose to 5C Aldose
-Enzyme: ribose phosphate isomerase |
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Overal reaction of oxidative portion of PPS
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G6P +2NADP+ + H20 -> Ribose-5-P + CO2 + 2NADPH + 2H+
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Nonoxidative portion of PPS
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THree pentose phosphates are transformed into two hexose phosphates and a triose phosphate
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Non-oxidative phase enzymes
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Ribulose(P) 3-epimerase, transketolase, and transaldolase
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What is stage 3 of respiration?
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Electron transport and oxidative phosphorylation
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What is the aerobic acceptor
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Oxygen
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Mitochondria
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-football shaped
-1-2u -electron transport and oxidative phosphorylation occur here |
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Mitochrondria outer membrane
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permeable to small molecules
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Mitochondira inner membrane
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-electron transport enzymes embedded
-ATP synthase embedded -Impermeable |
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Mitochrondira Matrix
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TCA enzymes are located here as well as enzymes for ATP, ADP, NAD+, NADPH, Mg2+
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What does the electron transport system do?
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Converts energy in NADH and FADH2 into ATP
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How do electrons flow in the ETS?
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Along an energy gradient via carriers in one direction from hi reducing potential to low reducing potential.
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What does high reducing potential mean?
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Greater tendency to donate electrons
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Overall energy trop from NADH to O is?
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1.14 Volts
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Free energy change from NADH to O
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-220 KJ/Mole
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NADH Dehydrogenase Complex 1
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-NADH-CoQ oxioreductase
-Contains FMN/FMNH2 and an Iron sulfur center as electron carriers -NADH is substrate -CoQ is a second substrate |
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CoQ =?
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Ubiquinone
-lipid in inner membrane -carries electrons -polyisoprene tail -move freely |
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Succinate Dehydrogenase Complex II
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Enzyme: Succinate CoQ oxioreductase
-Second entry into electron acceptor -Substrate is succinate -FAD is reduced -Contains Iron center -CoQH2 carries electrons to cytochrome b |
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How many entry points for NADH have?
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Two entry points
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SUccinate dehydrogenase-Complex II
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Yields CoQH2
-Second entry into electron transport -Substrate is Succinate -Enzyme: Succinate CoQ reductase -FAD is reduced -Contains Iron Sulfur Center |
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What does CoQH2 do?
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Carries electrons to cytochrome b
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What do cytochromes do?
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They carry electrons and contain a heme like group
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Where are cytochromes in respiration located?
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inner mitochondrial membrane
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What is the order of cytochromes?
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b, c1, c, a , a3
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Which cytochrome is mobile?
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Cytochrome C
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What is complex III?
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Cytochrome b an Fe-S and c1
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What is Complex IV?
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a+a3 or cytochrome c oxidase
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What is the only component that can interact with O2 in the ETS?
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Cytochrome a3
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Cytochrome C oxidase
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large protein that is a part of complex IV
-contains a and a3 subunits which have a heme A and Cu |
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What do heme A and Cu do?
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They work together to transfer electrons to oxygen which interacts with the A3 subunit of complex IV
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In respiration what is NADH converted to?
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FMN via NADH dehydrogenase
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What is FMN converted to in respiration?
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Fe-S
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What is Succinate converted to in respiration?
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FAD via succinate dehydrogenase
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Cytochrome C oxidase
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large protein that is a part of complex IV
-contains a and a3 subunits which have a heme A and Cu |
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What is FAD converted to?
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Fe-S
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What do heme A and Cu do?
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They work together to transfer electrons to oxygen which interacts with the A3 subunit of complex IV
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What is Fe-S converted to?
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Coenzyme Q
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In respiration what is NADH converted to?
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FMN via NADH dehydrogenase
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Complex I can jump to?
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Complex V where is produces ATP
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What is FMN converted to in respiration?
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Fe-S
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CoQ gets converted to?
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Cytochrome B in complex III
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What is Succinate converted to in respiration?
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FAD via succinate dehydrogenase
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What is FAD converted to?
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Fe-S
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Cyt B gets converted to
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Fe-S
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What is Fe-S converted to?
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Coenzyme Q
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Cytochrome C oxidase
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large protein that is a part of complex IV
-contains a and a3 subunits which have a heme A and Cu |
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Complex I can jump to?
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Complex V where is produces ATP
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CoQ gets converted to?
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Cytochrome B in complex III
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What do heme A and Cu do?
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They work together to transfer electrons to oxygen which interacts with the A3 subunit of complex IV
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Cyt B gets converted to
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Fe-S
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In respiration what is NADH converted to?
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FMN via NADH dehydrogenase
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What is FMN converted to in respiration?
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Fe-S
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What is Succinate converted to in respiration?
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FAD via succinate dehydrogenase
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What is FAD converted to?
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Fe-S
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What is Fe-S converted to?
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Coenzyme Q
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Complex I can jump to?
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Complex V where is produces ATP
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CoQ gets converted to?
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Cytochrome B in complex III
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Cyt B gets converted to
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Fe-S
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Cyt c1 gets converted to?
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Cytochrome C
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Fe-S from complex II can go straight to?
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Complex V- producing ATP
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Cyt C gets converted to
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Ctytochrome A
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Cyt A gets convereted to
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Cyt A3
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Cyt A can go directly to?
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Complex V- producing ATP
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Cyt A3 gets converted to
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Produces H2O
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Amytal, rotenone
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Inhibitor that stops Fe-S (from succinate) from being converted to Co-Q
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Antimycin A
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Inhibitor that stops Cytochrome B from being converted to Fe-S
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CN,CO
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Ihibitor that stops production og Cytochrome A3 (does not produce O2)
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What is NADH oxidized by?
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CoQ
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What is cytochrom B oxidized by?
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Cytochrome C1
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What is Cytochrome a oxidized by?
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O2
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Oxidative Phosphorylation
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Production of ATP using transfer of electrons for energy
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What are the requirements for energy coupling?
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Intact mitochondria, Pi, ADP, NADH
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How is coupling accomplished?
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Coupling occurs indirectly in that a proton gradient is generated across the inner mito membrane
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What is the ATP machinery?
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F0F1 ATP Synthase Complex
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Where is the ATP Synthase complex located?
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inner mitochondrial membrane
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What side is ATP synthesized on?
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MAtrix side
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Chemiosmotic theory
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A proton gradient is created using energy from electron transport which is accomplished by the proton pumping of complexes I,III,IV from matrix to intermembrane space
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How is ATP synthase driven?
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The proton motive force dictates that the protons have a tendency to move from the intermembrane space back to the matrix which drives ATP production
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What are the proton pumps?
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Complexes I, III, IV
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What subunit rotates through F1
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gamma
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What turn is needed for ATP release?
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gamma does a 1/3 turn
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From what unit in gamma is ATP released?
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O
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What compound uncouples?
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DNP (2,4,-Dinitrophenol)
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What compound blocks flow of protons?
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Oligomycin blacks H+ flow through Fo which blocks oxidative phosphorylation
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What is a natrual uncoupler?
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Brown fat cells
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Dihydroxyacetone phosphate shuttle yields?
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2ATP/NADH
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Malate shuttle yields?
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3ATP/NADH
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What is the major source of energy in the body?
|
Fatty Acids in triglycerides
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What tissues use fatty acids for energy
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liver, heart, skeletal muscles
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What breaks down dietary fats
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bile salts and pancreatic lipases
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How are triglycerides broken down?
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By lipases
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Hormone sensitive lipases
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-Hydrolyzes triglycerides to glycerol and fatty acids
-Hormonally regulated - |
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What carries fatty acids in the bloodstream?
|
Albumin
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How is hormone sensitive lipases regulated?
|
Epinephrine or Glucagon stimulates adenylyl cyclase
-Which stimulates cyclic AMP -Which stimulate protein kinase -Which becomes active protein kinase A- -Which uses ATP to convert lipase to its active form |
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How are hormone senstitive lipases regulated (inhibitied)?
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Insulin stops adenyly cyclase from being activated
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Glycerol metabolism steps
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Glycerol + ATP goes to G3P which gets converted to dihydroxyacetone phosphate which enters glycolysis
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Glycerol metabolism enzymes
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Glycerol to G3P uses Glycerol Kinase
-G3P to dihydroxyaceton uses glycerol phsphate dehydrogenase |
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How are fatty acids activated?
|
Fatty acids must be converted to fatty acyl CoA
-occurs via fatty acyl CoA synthetase -Uses ATP |
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Cyt c1 gets converted to?
|
Cytochrome C
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Fe-S from complex II can go straight to?
|
Complex V- producing ATP
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Cyt C gets converted to
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Ctytochrome A
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Cyt A gets convereted to
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Cyt A3
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Cyt A can go directly to?
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Complex V- producing ATP
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Cyt A3 gets converted to
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Produces H2O
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Amytal, rotenone
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Inhibitor that stops Fe-S (from succinate) from being converted to Co-Q
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Antimycin A
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Inhibitor that stops Cytochrome B from being converted to Fe-S
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CN,CO
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Ihibitor that stops production og Cytochrome A3 (does not produce O2)
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What is NADH oxidized by?
|
CoQ
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Fatty Acid Activation
|
Fatty acids get converted to fatty acyl Coa via fatty acyl CoA synthase
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Fatty Acid Activation enzyme
|
Fatty acyl CoA synthetase or tiokinase
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How many steps are there in Fatty Acid Activation
|
Two
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Step 1 of fatty acid activation
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Fatty acid gets converted to fatty acyl adenylate which is enzyme bound
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Step 2 fatty acid activation
|
Fatty acyl adenylate gets converted to fatty acyl CoA
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Where are fatty acids stored
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cytosol
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How are fatty acids transported into the mitochondria
|
via carnitine and carnitine acyl transferases
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B-oxidation steps
|
Oxidation between and alpha and bB carbon
2) hydration across a double bond 3) oxidation of a ketone 4) tiolysis releases acetyl-CoA |
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B-Oxidation
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Two carbon groups get removed from the carboxyl terminal of the fatty acid acetyl CoA
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How are fatty acids degraded?
|
By the release of C2 fragments as acetyl CoA
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Energy Yield from the Oxidation of Fatty Acids
|
FAD->FADH2: 2 ATPS
NAD+->NADH: 3ATPS acetyl CoA->TCA: 12 ATPS TOTAL: 17 ATPS per round of B-oxidation |
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Where does fatty acid degredation occur?
|
In the mitochondria
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What does fatty acid degredation yield?
|
Acetyl CoA and reduced co-factors
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How much energy does palmitate oxidation yield?
|
129 ATPS
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What does odd chain fatty acid oxidation yield?
|
Three carbon propionyl CoA
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What does metabolism of propionyl CoA use?
|
Biotin and Vitamin B12
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What does propionyl CoA get converted to?
|
Succinyl CoA
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Odd Chain Fatty Acid Oxidation
|
Produces three carbon propionyl CoA
- |
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|
Odd Chain Fatty Acid Enzyme
|
Propionyl CoA carboxylase (biotin)
|
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Ketogensis
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Process where acetyl CoA is converted into ketone bodies
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What are ketone bodies
|
Acetoacetic acid, B-hydroxybutyrate and acetone
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Where are acetoacetic acid and B-hydroxybutyrate dispersed to
|
Muscles and brain to be used for ATP production
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What is a key intermediate in ketogensis?
|
HMG-CoA (hydroxymethylglutaryl CoA)
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Ketogensis steps
|
1) Two acetyl CoA get condensed by thiolase
2) Another Acetyl CoA gets added by HMG-CoA synthase 3)An acetoacetate is split off by HMG-Coa lysae 4)Acetoacetate can get converted to acetone or B-hydroxybutyrate |
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Step 1 Ketogensis enzyme
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Thiolase
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Step 2 Ketogensis enzyme
|
HMG-CoA synthase
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Step 3 Ketogensis enzyme
|
HMG-CoA lyse
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Step 4 Ketogensis enzyme
|
acetoacetate decarboxylase or B-hydroxybutarate dehydrogenase
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Fate of ketone bodies
|
Liver: undergoes fatty acid oxidation
Brain/Muscle: TCA |
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Overall fatty acid biosynthesis
|
14 NADPH+8acetyl CoA+ 7ATP-> c16 +14 NADP+ + 8CoA + 7ADP + 7Pi + h20
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What is the key factor that begins the fatty acid biosynthesis process?
|
acetyl CoA carboxylase which uses a biotin cofacter
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What is required for Acetyl CoA Carboxylase?
|
CO2, ATP and Biotin
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What is rate limiting in fatty acid biosynthesis?
|
Acetyl CoA carboxylase
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Regulation of Fatty Acid Biosynthesis
|
Inactivated by phosphorylation
Activated by dephosphorylation Citrate increases activity allosterically |
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How does chain elongation occur in fatty acid biosyntheses
|
The fatty acid bound to the carrier protein, acyl carrier protein (ACO)
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Fatty Acid Synthase
|
Complex of enzymes that adds C2 units to a gorwing fatty acid chain.
-Uses NADPH -Homodimer of a polyfunctional protein |
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Where does Malonyl attach in fatty acid synthase?
|
To the ACP
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Where does that Acetyl attach
|
to the SH group
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Steps in fatty acid synthase
|
Acetyl displaces carboxylic acid (as CO2) adding two carbons
-Then the ketone is reduced to hydroxide using NADPH -Then dehydration occurs forming a double bond -Then the double bond is hydrogenated using NADPH -Then the acyl group is transferred from the ACP to the SH |
|
|
What are sources of Acetyl Coa
|
pyruvate dehydrogenase
breakdown of fatty acids catabolism of ketogenic amino acids |
|
|
What is the carrier of acetyl groups?
|
Citrate
|
|
|
Citrate transportation enzymes
|
Uses citrate synthase and citrate lyse
|
|
|
Citrate transportation steps
|
OAA to Citrate via citrate synthase
-Citrate to OAA via citrate lyase |
|
|
Where does fatty acid oxidation occur?
|
Mitochondria
|
|
|
Where does fatty acid synthesis occur?
|
Cytoplasm
|
|
|
What are the initial substrates of fatty acid oxidation?
|
Fatty acyl CoA
|
|
|
What are the inital substrates of fatty acid synthesis?
|
Acetyl CoA or malonyl CoA
|
|
|
What is the tioester linkage for ffatty acid oxidation?
|
CoASH
|
|
|
What is the thioester linkage for fatty acid synthesis?
|
Protein SH (ACP)
|
|
|
What are the coenzymes for fatty acid oxidation?
|
FAD and NAD+
|
|
|
What are the coenzymes for fatty acid synthesis?
|
NADPH
|
|
|
Bicarbonate dependence for fatty acid oxidation and synthesis
|
Oxidation: NO
Synthesis: YES |
|
|
Energy state for fatty acid oxidation
|
High ADP
|
|
|
Energy state for fatty acid synthesis
|
High ATP
|
|
|
Is fatty acid oxidation activated by citrate?
|
NO
|
|
|
Is fatty acid Synthesis activated by citrate?
|
YES
|
|
|
Is fatty acid oxidation inhibited by Acyl CoA?
|
NO
|
|
|
Is fatty acid synthesis inhibited by Acyl CoA?
|
YES
|
|
|
When is fatty acid oxidation highest?
|
During fasting and starvation
|
|
|
When is fatty acid synthesis highest?
|
Ate carbs
|
|
|
How is lipid metabolism regulated?
|
-Hormonally
-Metabolically by allosteric control -Expression control |
|
|
What is the key regulatory enzyme for lipid metabolism?
|
Acetyl CoA Carboxylase
|
|
|
How is acetyl Coa carboxylase inhibited and activated?
|
Ihibited by glucagon (phosphorylation)
Activated by Insulin-dephosphorylation and by Citrate |
|
|
Hormonal control (fats) with glucagon
|
Glucagon binds to the plasma membrane and causes phosphorylation with protein kinases:
-Acetyl Coa carboxylase-inhibited -Hormone sensitive lipase: Activated -Pyruvate Dehydrogenase:inhibited -decreases fatty acid synthesis -increases mobilization of stored fats -increased gluconeogensis |
|
|
What effects does glucagon have
|
-Decreases fatty acid synthesis
-Increases mobilization of stored fats -Increased gluconeogenesis |
|
|
Hormonal control with insulin
|
-Causes dephosphorylation
-Acetyl CoA carboxylase: activated -Hormone sensitive lipase: inactivated -Pyruvate dehydrogenase:activated -Increase fatty acid synthesis -Decreases mobilization of stored fats -Decrreased gluconeogensis |
|
|
What effects does insulin have
|
Increases fatty acid synthesis
Decreases mobilization of stored fats Decreased gluconeogensis |
|
|
What does Palmitoyl CoA inhibit
|
alloseterically inhibits acetyl CoA carboxylase
|
|
|
What does malonyl Coa inhibit
|
It inhibits carnitine palmitoyl transferase
|
|
|
What inhibits carniting palmitoyl transferase?
|
Malonyl CoA
|
|
|
What is activates Acetyl CoA Carboxylase allosterically?
|
Citrate
|
|
|
Uses of cholesterol
|
membranes, precursor for bile acids, precursor to steroid hormones, and precursor to Vitamin D
|
|
|
Mevalonate pathway steps
|
1) Two aceytl groups are condensed
2) Then another Acetyl group is added from Acetyl CoA 3) HMG-COA reductase makes mevalonate |
|
|
HMG-CoA Reductase
|
Beta-hydroxy-beta-methylglutyral-CoA reductase
|
|
|
What is the rate limiting step in cholesterol synthesis?
|
Making mevalonate
|
|
|
What is the key regulation step of cholesterol synthesis?
|
Making mevalonate
|
|
|
What is used to make isoprene from mevalonate?
|
Three kinases and a decarboxylase
|
|
|
Step 3 in Mevalonate cholesterol synthesis
|
Two isoprene units join head to tail to form geranyl phosphate (C10)
-reaction driven by: pyrophophate hydrolysis |
|
|
Step 4 in Mevalonate cholesterol synthesis
|
Another isoprene is added head to tail to form farnesyl pyrophsphate (C15)
-reaction driven by:pyrophsphate hydrolysis |
|
|
Enzyme for Step 3 and Step 4 of mevalonate cholesterol synthesis
|
Prenyl transferase
|
|
|
Step 5 in Mevalonate cholesterol synthesis
|
2 farnesyl units joined head to head to form squalene
-enzyme: squalene synthase -Reduced by NADPH and 2 pyrophsphates released |
|
|
Step 6 and othes in mevalonate cholesterol synthesis
|
Squalene monooxygenas produces epoxide using oxygen
-then cholesterol |
|
|
Progesterone
|
Steroid precursor and regulates pregnancy
|
|
|
Estrone/Estradiol
|
female development hormones
|
|
|
Testosterone
|
male sex hormone that helps develop males
|
|
|
Cortisol
|
Glucocorticoid that promotes gluconeogenesis and is an anti-inflammatory
|
|
|
Aldosterone
|
mineralcorticoid that regulates ion balance
|
|
|
Lipoproteins
|
High molecular weight complexes of specific proteins and lipids which transport lipids in the blood
|
|
|
Lipoprotein classes
|
-Chylomicrons
-Very low density lipoproteins -Low density lipoproteins -Intermediate density lipoproteins -High Density Lipoproteins |
|
|
Very low density lipoproteins
|
VLDL: are the richest inlipid and lowest in protein
-Deliver triglycerides to tissue |
|
|
Chylomicrons
|
made in the intestines and deliver triglycerides to peripheral tissues
|
|
|
Intermediate density lipoprotein and Low dentisty lipoprotein
|
Intermediate in density
LDL carries cholesterol to peripheral tissues |
|
|
High Density Lipoproteins
|
most dense
made in the liver and intestine remove cholesterol from peripheral tissues |
|
|
Chylomicrons and VLDL are synthesized with what proteins, which do what?
|
apoB48 and apoB100 which are attached to the proteins during TG metabolism
|
|
|
Recognition of LDL and IDL
|
apoB and apoE receptors on the surfaces of cells can sense when the LDL and IDL are depleted of TGs and cause the cell to take up the LDL/IDL bu receptor mediated endocytosis
|
|
|
Enzyme associated with HDL
|
LCAT (lecithin cholesterol acyl transferase)
-enables the HDL to transfer fatty acyl groups from phosphatidyl choline to cholesterol to form cholesterol esters |
|
|
Where do cholesterol esters can transferred
|
They go from HDL to the liver of VLDL for processing
|
|
|
Cholesterol Biosynthesis Regulation
|
-Synthesis of LDL receptors decreases with increased cholesterol
-Synthesis of HMG CoA reductase decreased with increased cholesterol -Mediated by inhibition of gene transcription |
|
|
Atherosclerosis
|
Disease where artery walls become less elastic and thicker with fatty material
|
|
|
What is rate limiting in cholesterol biosynthesis
|
HMG-CoA reductase
|
|
|
Compactin
|
HMGCoA Reductase inhibitor: Changes R1/R2 to H
|
|
|
Simvastatin (Zocor)
|
HMGCoA Reductase inhibitor: Changes R1/R2 to CH3
|
|
|
Pravastatin (Pravachol)
|
HMGCoA Reductase inhibitor: Changes R1/R2 to H and OH
|
|
|
Lovastatin (Mevacor)
|
HMGCoA Reductase inhibitor: Changes R1/R2 to H and CH3
|
|
|
Hormone Sensitive Lipase
|
In fat cells, hydrolyzes TG to release fatty acids, controlled by glucagon, epinephrine and insulin
|
|
|
Albumin
|
Carries fatty acids in the blood stream
|
|
|
Glycerol Kinase
|
Produces G3P
|
|
|
Glycerol 3 Phosphate Dehydrogenase
|
Oxidizes G3PD to DHAP for glycolysis
|
|
|
Fatty acyl-CoA synthetase (tiokinase )
|
Uses ATP and CoA to activate fatty acids
|
|
|
Carnitine
|
Small molecule used to transport fatty acids into mitochondria
|
|
|
Carnitine Acyl Transferase I and II
|
adds fatty acyl to carnitine from fatty acyl CoA and removes
|
|
|
Acyl-Coa Dehydrogenase, hydratase and OH Acyl-CoA dehydrogenase
|
dehydrogenase oxidise hatty acyl CoA, hydrates oxidize to ketone at beta position
|
|
|
Acyl-CoA acetyltransferase
|
removes acetyl-CoA by attack of CoA leaving a shortened acyl CoA
|
|
|
Propionyl-CoA Carboxylase
|
adds CO2 to propionyl CoA to form methylalonyl-CoA, uses ATP, Biotin and B12
|
|
|
Ketone Bodies
|
Acetoacetone, D-beta hydroxybutyrate and acetone
|
|
|
Thiolase
|
puts 2 acetyl CoAs together to form acetoaceytl-CoA
|
|
|
HMG-CoA Synthase
|
adds 3rd acetyl-CoA to produce HMG-CoA, also in Cholesterol synthesis
|
|
|
D-Beta-hydroxybutyrate dehydrogenase
|
oxidizes acetoacetate to D-beta hydroxybutyrate
|
|
|
Beta-ketoacyl CoA transferase
|
exchanges acetoacetyl for succinyl in succinyl-CoA
|
|
|
Diabetic Ketosis
|
lare increase in levels of circulating ketone bodies in untreated diabetes
|
|
|
Acetyl CoA carboxylase
|
carboxylates acetyl-CoA to make malonyl-CoA, uses ATP, Biotin and is regulated and rate limiting
|
|
|
Acyl Carrier Protein (ACP)
|
Has a prosthetic group, part of fatty acid synthase, carries malonyl-CoA and Acyl-Coa
|
|
|
Fatty Acid Synthase
|
homodimer of large polypeptide that synthesis fatty acids
|
|
|
Citrate-malate shuttle
|
transports acetyl-CoA from mit to cytosol
|
|
|
Citrate synthase and citrate lyase
|
produces acetyl-CoA carrier in mit and releases acetyl-CoA in cytosol
|
|
|
Function of phospholipids
|
-Membrane consitutents
-Precursors of triglycerides -Storage of polyunsaturated fatty acids -Prostaglandin precursors -Lung surfactants |
|
|
Where are the glycerol units derived for phospholipids and triglycerides
|
They come from the glycolytic pathway or salvage of glycerol
|
|
|
Where are the fatty acids derived from?
|
Fatty acid biosynthetic pathway
|
|
|
Glycerol Kinase is only present in?
|
Kidney and Liver
|
|
|
Glycerol Phosphate production
|
Glucose goes to Dihydroxyacetone phosphate which gets converted to G3P by G3P dehydrogenase
|
|
|
Glycerol phosphate production
|
Glycerol to G3P via glyceral kinase
|
|
|
R1 in phospholipids favors..
|
Saturated fatty acids
|
|
|
R2 in phospholipids favors...
|
Unsaturated fatty acids
|
|
|
Where are phospholipids made?
|
On smooth ER and mitochondrial inner membrane
|
|
|
Intermediates for Strategy two to make phosphstidylcholine
|
diacylclycerol and CDP-Choline
|
|
|
Who uses Strategy 2
|
Mammals
|
|
|
Who uses strategy 1?
|
Eukaryotes
|
|
|
What does strategy 1 make?
|
Phosphatidyl inositol
|
|
|
Key intermediates for strategy 1
|
phosphatidic acid and inositol
|
|
|
Sources of amino acids
|
Dietary proteins, endogenous protein turnover, de novo protein synthesi
|
|
|
What does endogenous protein turnover do?
|
Removes misfolded proteins, removes old and damaged proteins, regulates cell metabolism, plays critical rols in cell cycle transitions
|
|
|
What is de novo protein sythesis used for?
|
Protein synthesis, adjust amino acid pools, energy source
|
|
|
Amount of amino acids for adults
|
.8g/kg
|
|
|
Essential Amino Acids
|
Phe, Arg, Trp, Thr, Ile, Met, His, Leu, Lys
|
|
|
Conditionally essential amino acids
|
Arg, Tyr (at low Phe), and Cys ( at low Met)
|
|
|
How are digestive proteins stored?
|
AS zymogens in the pancreas where they get secreted to the small intestine or lumen
|
|
|
What is trypsinogen activated by
|
enterokinase which is a protease
|
|
|
What does trypsin activate?
|
It activates chymotrypsinogen
|
|
|
What does zyomogen formation do?
|
Prevents autophagy and apoptisis
|
|
|
Pepsinogen
|
Active:Pepsin
Located: Stomach pH: 1-3 |
|
|
Chymotrypsinogen
|
Active: Chymotrypsin
Located: Intestine pH: 7 |
|
|
Trypsinogen
|
Active: Trypsin
Located: Intestine pH: 7 |
|
|
Procarboxypeptidase
|
Active: Carboxypeptidase
-removes one -cooh residue at a time |
|
|
How is chymotrypsinogen activated?
|
By proteolysis
|
|
|
Activation of pepsin is...
|
an autocatalytic process
|
|
|
A
|
Ion Dependence: Na+
AA's transported: Neutral AA |
|
|
ASC
|
Ion Dependence: Na+
AA's transported: Neutral AA |
|
|
L
|
Ion Dependence: Na+ independent
AA's transported: Branched chain and aromatic |
|
|
N
|
Ion Dependence: Na+
AA's transported: Nitrogen side chain (Glin, Asn, His, Lys, Arg) |
|
|
y+
|
Ion Dependence: Na+ independent
AA's transported: cationic |
|
|
Xag
|
Ion Dependence: Na+
AA's transported: Glutamate and Aspartate |
|
|
P
|
Ion Dependence: Na+
AA's transported: Proline |
|
|
Mammals nitrogen excretion
|
Ureotelic: Urea excreting
|
|
|
Birds
|
Uricotelic: Uric acid exreting
|
|
|
Fish
|
Ammonotelic: NH3 excreting
|
|
|
Humans excrete
|
Urea, small amount of uric acid and creatine
|
|
|
Rate of protein turnover depends on
|
the particular protein and metabolic state of the person
|
|
|
Two pathways of protein turnover
|
-Proteases in lysosomes and phagolysosomes
-Ubiquitin dependent pathway that works in conjunction with proteasomes |
|
|
True nitrogen balance
|
intake=excretion
|
|
|
Positive Nitrogen Balance
|
intake>excretion
|
|
|
Negative Nitrogen Balance
|
Excretion>Intake
|
|
|
When do you have a negative nitrogen balance?
|
Starvation, malnutrition, disease
|
|
|
When do you have a positive nitrogen balance?
|
growing, pregnancy, wound, convalescing adult
|
|
|
Transamination
|
Loss of an alpha amoino group to form an alpha keto-acid
-Uses transaminases or aminotransferases -Transfers the amino group to pyruvate of a-ketoglutarate to make alanine of glutamate -Fully reversible |
|
|
What amino acids are not transaminated
|
Proline/hydroxyproline (secondary amine)
Lysine (toxic) Threonine (toxic) |
|
|
Transaminases
|
-Requires cofactor of pyridoxal phosphate which comes from B6
|
|
|
Transaminase Mechanism
|
1) Aldimine forms
2)Aldimine convert to ketimine 3)Hydrolysis of ketamine |
|
|
Demination Reaction (Glutamate Dehydrogenase)
|
-Undergoes oxidative deamination by Glutamate Dehydrogenase
-Regenerates the amino acceptor a-keotglutarate |
|
|
Where is glutamate dehydrogenase located?
|
in the mitochondrial matrix
|
|
|
Glutamate Dehydrogenase
|
Performs oxidative deamination
-Uses NAD+ |
|
|
Allosteric control of Glutamate Dehydrogenase
|
-High ATP , GTP and NADH INHIBIT
-High ADP, GDP and free AA's ACTIVATES GDH |
|
|
Why do we need both L and D amino acid oxidases?
|
D-aminos in old proteins, and in old dried foods, and D has an antibacterial effect
|
|
|
Hydrolytic Deamination
|
-Non-oxidative deamination reaction
-Enzymes: glutaminase, asparginase, and histidinase -Yields ammonia |
|
|
Eliminative Deamination
|
-Forms a double bond eliminating an NH3
-Enzyme: Histidinase and Histidine ammonia lyase |
|
|
Glycogenic AAs are..
|
Can be converted to intermediates of the TCA cycle of Gluconeogenesis
|
|
|
Glycogenic AAs
|
Alanine, Aspartate, Glutamate, Cysteine, Glycine, Serine, Tryptophan, Glutamine, Asparagine, Isoleucine
|
|
|
Ketogenic AAs are...
|
AAs that can be converted to ketone bodies
|
|
|
Ketogenic AAs
|
Leucine and Lysince
|
|
|
Potentially ketogenic AAs:
|
Alanine, Cysteine, Glycine, Serine
|
|
|
AAs that are both glycogenic and ketogenic
|
Isoleucine, Phenylalaline, Tyrosine, Tryptophan, Threonine
|
|
|
Why is ammonia toxic?
|
Ammonia is toxic because it crossses membranes and can dissipate H+ gradients
-Deplete a-ketoglutarate inhibiting TCA activity |
|
|
How is ammonia assimiltation catalyzed?
|
Glutamate Dehydrogenase or Glutamine Synthase or Carbamoyl-Phosphate Synthetases 1 and 2
|
|
|
Glutamine Synthetase
|
-Major way to trap NH3
-Uses ATP and Glutamine Synthetase |
|
|
What does Gln do?
|
Inter-organ nitrogen shuttle that doesn't affect blood pH
|
|
|
E.Coli Glutamine Synthetase
|
-Unique mechanism relying on post translational modification
-Multisubunit complex that has 12 identical 50kDa subunits |
|
|
E.Coli Glutamine Synthetase Enzyme Info
|
-Enzyme catalyzed covalent interconversion
-Gln Synthetase has a tyrosyl residue outside it's active site -Residue forms phophodiester linkage with ATP |
|
|
What residue does E.Coli Gln Synthetase have?
|
Tyrosyl residue
|
|
|
Bacterial GS regulation
|
-GS adenylyation and deadenylylation is catalyzed by a single bifunctional enzyme that is regulated by PII protein.
|
|
|
PII protein
|
-Two forms
-UMP-PII activates deadenylyation -Deuridylylated-PII activates adenylylation |
|
|
PII protein regulation
|
PII uridylylation ihibited by Glutamine (activates adnylylation)
-PII uridylylation activated by a-ketoglutarate (activates deadenylyation) |
|
|
Regulation of Glutamine Synthetase (bacteria)
|
Weakly ihibited by eight metabolites that are direct glutamine end-products
-Gly,Ser,His,Ala,Carbamyl-P,Glucosamine, Try,AMP,CTP |
|
|
What metabolites weakly ihibit E.Coli Gln Synthetase?
|
Gly,Ser,His,Ala,Carbamyl-P,Glucosamine, Try,AMP,CTP
|
|
|
Carbamoyl-Phosphate Synthetase
|
-Form of ammonia assimilation
-High energy dependent reaciton -Occurs in two steps -Has enzyme bound intermediates -USes two ATP |
|
|
Carbamoyl-Phosphate Synthetase II
|
-Uses Glutamine in place of ammonia
-Removes NH3 from glutamine and transfers it through a tunnel to a biosynthetic subunit |
|
|
CPS-I Location
|
Mitochondria
|
|
|
CPS-II location
|
Cytosol
|
|
|
CPS-I Substrate
|
Ammonia
|
|
|
CPS-II Substrate
|
Glutamine
|
|
|
CPS-I Km for NH3
|
Low
|
|
|
CPS-II Km for NH3
|
Very High
|
|
|
CPS-I Km for glutamine
|
Doe not bind
|
|
|
CPS-II Km for glutamine
|
Very low
|
|
|
CPS-I Pathway
|
Urea
|
|
|
CPS-II Pathway
|
Pyrimidine Nucleotide
|
|
|
CPS-I Activator
|
N-acetyl glutamate ormithine
|
|
|
CPS-II Activatro
|
ATP and P-Ribosyl-PP
|
|
|
CPS-II Inhibitor
|
Purine nucleotides
Pyrimidines |
|
|
CPS-I Inhibitor
|
None
|
|
|
CPS-I Structure
|
Heterodimer
|
|
|
CPS-II Structure
|
Part of CAD polyprotein
|
|
|
Urea Cycle
|
-Occurs mainly in the Liver
-Nitrogen is transported between organs in organic forms -Highly energy dependent |
|
|
In mammals what is the main end product of the nitrogenous cycle?
|
Urea
|
|
|
Urea Reaction
|
CO2 + NH4 + 3ATP +Aspartate + h2o-> UREA + 2ADP + 2Pi+ PPi +fumarate +5H+
|
|
|
Urea enzymes
|
Ornithine Transcarbamoylase
Arginosuccinate Synthetase Argininosuccinate LYase -Arginase |
|
|
Urea cycle control
|
-High protein diets/fasting causes increase in urea cycle enzymes
-Glucagon induces synthesis of all five urea cycle enzymes -Arginine and Glutamate are two of the most powerful regulators of the urea cycle |
|
|
What is the first committing step fo the urea cycle?
|
CPS-1
|
|
|
NAGS
|
N-acetyl-glutamate synthase (NAGS)
|
|
|
NAGS synthesis
|
-Activated allosterically by arginine
-Two distinct domains-one if a c-terminal transferase domain -N-terminus arginine sensing domain |
|
|
NAGS deficiency
|
Leads to hyperammonemia
|
|
|
What restores/improves urea cycle function in the abscence of NAGS
|
N-carbamoylglutamate
|
|
|
Acinus
|
Structural organization and functional organization of cells into an acinus which involves differential management of nitrogen metabolism along the flow path of blood
|
|
|
Peri-portal hepatocytes in portal venule take up?
|
Gln
|
|
|
How many mols of NH3 are consumed in urea synthesis?
|
2 mol
|
|
|
Arginine
|
Produces Creatine and Creatinine
-Uses glycine amidinotransferase |
|
|
Glutamate
|
-Made by four reactions
:Transamination :Reductive Amination (via NH3 and Glutamine) :Hydrolysis |
|
|
Aspartate
|
-Formed by transamination of glutamate
-Formed by hydrolysis of asparagine |
|
|
Asparagine
|
-Formed from aspartate and Gln and ATP using asparagine synthetase
|
|
|
Alanine
|
Formed from transamination of pyruvate and glutamate
-Serves as a way to transfer ammonia nitrogen from organs to liver |
|
|
Proline
|
-Key step is reduction of glutamate to glutamate semi-aldehyde
|
|
|
Serine
|
-Made in tow pathways from 3-phosphoglycerate
|
|
|
Glycine
|
-Four pathways
-Glutamate to Glycine -Choline to Glycine -Ammonia to Glycine -Serine to Glycine |
|
|
Tyrosine
|
-Conditionally essential
-Two step catalytic process -Made from Phe -Enzyme: Phenylalanine Hydroxylase |
|
|
Deficiency in Phe Hydroxylase results in?
|
Phenylketonuria-high serum Phe and high urinary Phenyl pyruvate
|
|
|
PKU
|
1/1000 births
-autosomal recessive -phenyl rises to 1.3mM -Causes nerve damage -Treatable with diet |
|
|
Cysteine
|
-Conditionally essential amino acid
-Methionine is converted to S-adenosyl methionine -Which gets converted to S-adenosyl homocysteine -Converts to Homocysteine -Homocysteine to Cystathionine -To Cysteine |
|
|
Thyroxine biosynthesis
|
-Formed from the enzymatic action of thyroglobulin
-660 KDa protein - |
|
|
Iodination cannot occur with
|
free tyrosine
|
|
|
What does release of T3/T4 do?
|
Stimulates mitochondria
|
|
|
Metabolic actions of Thyroxine
|
Stimulate or ihibitspecific gene transcription
-Increase basal metabolic rate -Increase O2 consumption -Stimulate fat mobilization and increase plasma fatty acids -Plasma cholesterol and triglyceride levels are inversely correlated with thyroid hormone levels -Increase in free glucose by enhancing insulin dependent glucose uptake |
|
|
T3/T4 enters cells with the help of
|
ATP dependent transporters
|
|
|
T3
|
Triiodothyronin AKA The active hormone
|
|
|
T4
|
Tetraiodothyronine AKA Thyroxine
|
|
|
Amino acids that are neurotransmitters
|
Glutamate, Aspartate, D-Serine, Glycine
|
|
|
Where does heme biosynthesis occur?
|
In mitochondrial and cytosolic compartments
|
|
|
Where does the first step in heme synthesis occur?
|
In the mitochondria
|
|
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First step Heme Synthesis
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Succinyl CoA is condensed with glycine to form ALA
enzyme: ALA synthase |
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Second step Heme
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ALA goes to cytosol to produce porphobilinogen
enzyme: ALA Dehydrtase |
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Third step Heme
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Pophoilinogen is converted to hydroxymethyibilane
enzyme: PEG deaminase |
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Fourth step heme synthesis
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Hydroxymethylbilane froms Uroporphrynogen III
Enzyme: Uro-gen III synthase |
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Fifth step heme synthesis
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Urophorphigen II forms coproporphrynogen III
enzyme: Urogen III decarboxylase |
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Step 6 heme
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OCCURING UN CYTOSOL
Coproporphrynogen III forms protophorphrynogen IX Enzyme: Cop gen III oxidase |
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Step 7 heme
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Protoporphrynogen IX forms Protophorphyrin IX
enzyme: protogen IX oxidase |
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What inserts FE(II) into protoporphyrin IX to form HEME
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Ferrochelatase
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What does lead produce
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anemia by inhibiting heme synthesis
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Metabolic requirements for nucleotide synthesis
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-Dietary intake of RNA and DNA
-Salvage of cellular constitutions -de novo nucleotide synthesis |
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Endonucleases
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Cleave P-O bonds within nucleic acid chains
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Exonucleases
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Cleave P-O bonds at the end of nucleic acid chains
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What do salvage and de novo synthesis produce?
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nucleoside-5-monophosphates
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PRPP=
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5-phosphoribosyl-1-pyrophosphate
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PRPP is used for
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Purine biosynthesis and salvage reactions
-is an activated sugar intermediate |
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Where does purine synthesis occur
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Liver
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What is the first fully formed nucleotide?
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inosin 5-mono-P
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Synthesis of IMP requires
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1 mol CO2, 1 mol Asp, 2 mol formate
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1st /2nd step purine biosynthesis
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Formation of phosphoribosylamine and glycinamide ribonucleotide (GAR)
-glutamine hydrolysis and displacement of PPi -amide bond formation |
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3rd step purine bio
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Formation of formylglycinamide ribonucleotide (FGAR)
enzyme: formyl transfer -formyl transfer |
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4th/5th Step Purine Bio
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Formation of formylglycinamidine ribomnucleotide and aminoimidazole ribonucleotide (AIR)-joins aspartate as an amide bond
--glutamine hydrolysis and displacement of PPi -ring closure |
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6th step purine biosyntheis
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Formatio of aminoimidazole ribonucleotide (CAIR)
--adding a carboxamide |
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7th step purine bio
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Formation of Succinyl-CAIR (SCAIR)
-joins aspartate as amide bond |
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8th STep Purine Bio
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Formation of aminoimidazole-carboamide ribonuceltoide (AICAR)
-elimination reaction |
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9th Step Purine biosynthesis
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Formation of formyl-aminoimidazole carboamide ribonucleotide
-formyl transfer |
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10th step purine formation
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Formation of inosine 5 monophsphate
-ring closure |
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Conversion of IMP to AMP enzyme step 1
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Adenylosuccinate synthetase
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Conversion of IMP to AMP enzyme step 2
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Adenylsuccinate lyase
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Conversion of IMP to GMP enzyme step 1
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IMP dehydrogenase
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Conversion of IMP to GMP enzyme step 2
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GMP Synthase
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What provides energy for AMP synthesis?
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GTP
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What provides energy for GMP synthesis
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ATP
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Enzyme to go from AMP to IMP
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Adenylosuccinate Synthetase
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Each turn of the PN cycle converts what into what?
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Aspartate into fumarate and ammonia
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What does fumarate feed
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TCA cycle
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What does ammonia feed?
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Raises pH and stimulates glycolysis and TCA
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What is the only source of anaplerotic substrate
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Fumarate generation from PN cycle
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WHat do anaplerotic substrates do?
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Increase TCA cycle activity
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Muscle Specific AMP deaminase isoenzyme is known as
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myoadenylate deaminase
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What do deficiencies in myoadenalate deaminase do
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result in post-excercise fatiguem cramping, mylagias
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Lesch-Nyhan syndrome
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A deficiency in HGPRT(hypxanthine guanine phosphoribosyl)
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Gout
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Condition that occurs from precipitation of uric acid
-crystals form in joints -stimulate interleukins |
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What drug treats gout
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allpurinol
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Carbamoyl-P Synthetase
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-160kDa
-Small subunit is 42kDa and site of glutamine hydrolysis -100A tunnel where NH3 is transferred |
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Pyramidine Biosynthesis Step 1
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-Formation of carbamoyl-phosphate
-enzyme: cabamoyl-P-synthetase |
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Pyramidine Biosynthesis Step 2
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Formation of carbamoyl-aspartate
-enzyme: ATCase |
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Pyramidine Biosynthesis Step 3
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-Formation of dihydroorotate
Enzyme: Dihydroorotase |
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Pyramidine Biosynthesis Step 4
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Formation of orotate
Enzyme: Dihydrooronate dehydrogenase |
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Pyramidine Biosynthesis Step 5
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Formation of Orotidine 5-monophosphate (OMP)
enzyme: pyrimidine phosphoribosyl transferase |
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Pyramidine Biosynthesis Step 6
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Formation of uridine 5-monophsphate (UMP)
-enzyme: OMG decarboxylase -removes CO2 |
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CTP is a...
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feedback inhibitor of ATCase
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Bacterial Aspartate Transcarbamoylse
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-Three catalytic subunits
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CTP Synthetase
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CTP formed directly from UTP
coopoerative enzyme Activated by GTP (purine) |
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Human CS-I
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essential for phohpholipid biosynthesis
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Human CS-II
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rate limiting enzyme in pyramidine precursors
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Ribonucleotide Reductase (RNR)
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Converts ribonucelotides to 2-deoxy-ribonucleotides
-two iron center -performs irreversible reaction -only enzyme generating deoxyribonucleotides |
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How is DTTP made?
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Thymidylate synthase
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What does Dttp do
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converts dUMP to dTMP
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Marasmus
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-wasting away due to malnutrition or inadequate adsorption
-dry skin -loose folds -fretful -rritable -PEM protein energy malfunction |
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Kwashiorkor
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-childhood protein energy malnutrion
-edema, irritability, ulcerating, enlarged liver |
