ch 10 - Carbohydrate Metabolism II Flashcards
Krebs cycle
also called citric acid cycle or the tricarboxylic acid (TCA) cycle. In mitochondria. Main function: oxidation of acetyl-CoA to CO2 and H2O. Also produces high energy e-carrying molecules NADH and FADH2.
Acetyl-CoA
obtained through the metabolism of carbs, fatty acids and amino acids. Key molecule in crossroads of many metabolic pathways
pyruvate dehydrogenase complex (review from ch 9)
located in mitochondrial matrix; multienzyme complex that catalyzes oxidation of decarboxylation of pyruvate in the mitochondrion (pyruvate is a product of glycolysis of glucose)
five enzymes that make up pyruvate dehydrogenase complex
pyruvate dehydrogenase (PDH), dihydrolipyl transacetylase, dihydrolipoyl dehydrogenase, pyruvate dehydrogenase kinase, and pyruvate dehydrogenase phosphatase final two regulate action of PDH
coenzyme A (coA)
a thiol, containing an -SH group, resulting in formation of thioester which contains sulfur instead of typical oxygen ester -OR. This is very energy taxing but when hydrolyzed it gives off so much energy that it can drive other reactions such as citric acid (Krebs) cycle forward
Order of pyruvate dehydrogenase complex enzymes needed to catalyze acetyl-CoA formation
- Pyruvate dehydrogenase (PDH) - pyruvate oxidized yielding CO2 while remaining 2-C molecule binds covalently to thaimine pyrophosphate
- Dihydrolipoyl transacetylase - 2-C molec from previous transferred to lipoic acid which creates an acetyl group which binds to acid via thiolester linkage. Then this catalyzes the CoA-SH interaction with new thioester link, causing transfer of an acetyl group to form acetyl-CoA.
- Dihydrolipoyl dehydrogenase: after previous step lipoic acid is in reduced state. FAD(flavin adenine dinucleotide) reoxidizes it and it aids in future acetyl-CoA formation. FAD is reduced to FADH2 in the process. And reoxidized in the future while NAD is reduced to NADH
Fatty Acid oxidation (beta-oxidation)
in cytosol, process called activation - thioester bond forms bt carboxyl groups of fatty acids and CoA-SH. Activated fatty acyl-CoA taken to intermembrane space of mito. then transferred to carnitine by transesterification. Then acyl-carnitine, it crosses the inner membrane and transfers fatty acyl group to mitochondrial CoA-SH. Once acetyl-CoA is formed in matrix beta-oxidation can occur, which removes 2-C fragments from the carboxyl end
Amino acid catabolism
used to form acetyl-CoA. must lose their amino group via transamination, C skeletons then form ketone bodies. These amino acids are called ketogenic
Ketones to form acetyl-CoA
Acetyl-CoA is normally used to produce ketones when pyruvate dehydrogenase is inhibited but reverse rxn can occur also
Alcohol to form acetyl-CoA
in moderate amounts the enzymes alcohol dehydrogenase and acetaldahyde dehydrogenase convert this to acetyl-CoA; used to synthesize fatty acids because this rxn causes a build up of NADH which inhibits the Krebs cycle.
overall rxn of pyruvate dehydrogenase
pyruvate + NAD+ + CoA-SH -> acetyl-CoA + CO2 + NADH + H+
NADH and FADH2 (reminder)
energy carriers
Citric Acid Cycle overview
reminder: does not require O2 directly but will not proceed w/o it because NADH and FADH2 will not mulate. pyruvate (glucose and amino acids) with PDH then forms acetyl-CoA - then citrate and cis-Aconitase forms isocitrate+NAD+ andiocitrate dehydrogenase forms NADH, CO2 and alpha-Ketoglutarate; alpha-Ketoglutarate + NAD+ via alpha-Ketoglutarate dehydrogenase = NADH, CO2 and Succinyl-CoA; Succinyl-CoA + GDP+Pi via succinyl-CoA synthetase = GTP and succinate; succinate + FAD and succinate dehydrogenase (complex II) = Fumarate and FADH2; Fumarate forms malate and fumarase; Malate forms oxaloacetate and NADH and NAD+ via malate dehydrogenase; oxaloacetate feeds back into the cycle and citrate synthase
Step 1 of citric acid cycle
citrate formation:
acetyl-CoA and oxaloacetate form citryl-CoA as an intermediate via condensation rxn. Hydrolysis of citryl-CoA = citrate and CoA-SH. This is catalyzed by citrate synthase
acetyl-CoA + oxaloacetate + H2O -> citrate + CoA-SH + H+
Synthases vs synthetases
synthases are enzymes that form new covalent bonds w/o needing significant energy. Synthetases create new covalent bonds with energy input.
Step 2 of citric acid cycle
citrate isomerized to isocitrate:
citrate isomerized to 1 of 4 isomers of isocitrate. Citrate binds at 3 points to aconitase enzyme, water is lost = cis-aconitate; water is added back to form isocitrate which is a metalloprotein and requires Fe2+.
citrate ->(aconitase, H2O in and out) (aconitase, H2O in and out)
Step 3 of citric acid cycle
alpha-Ketoglutarate and CO2 Formation
Isocitrate from step 2 oxidized to oxalosuccinate by isocitrate dehydrogenase. oxalosuccinate decarboxylated to form alpha-ketoglutarate and CO2. First of two Cs from cycle is lost and first NADH produced from intermediates in cycle.
Isocitrate with NAD+ -> NADH + H+ and oxalosuccinate with H+ -> CO2 and alpha-ketoglutarate
rate-limiting enzyme of the citric acid cycle
isocitrate dehydrogenase
step 4 of citric acid cycle
succinyl-CoA and CO2 Formation:
carried out by the alpha-ketoglutarate dehydrogenase complex (similar in mechanism, cofactors and coenzymes to pyruvate dehydrogenase (PDH) complex). alpha-ketoglutarate and CoA come together to give off second and last CO2 lost in cycle. Reduced NAD+ gives another NADH.
alpha-ketoglutarate with CoA-SH, NAD+ ->(alpha-ketoglutarate dehydrogenase complex/TPP, lipoic acid, Mg2+)-> succinyl-CoA + CO2