106. THE KREBS CYCLE 



The Krebs Cycle (tricarboxylic acid cycle) l8 a major pathway for the final (aerobic) oxidation of carbohydrates, fats, and pro- 

 teins. These three nutrients are channeled into the cycle via their two key metabolites, pyruvate and acetyl-CoA ("active ace- 

 tate"). Each "revolution" of the cycle oxidizes 1 mole (59 g) of acetate to CO2 and H2O, with release of approximately 200 kllo- 

 calorles of energy. A portion of the released energy (approximately lAA kilocalorles) enters the phosphate energy pool as ATP. 

 Twelve moles of ATP are formed from ADP and PO^, (by energizing PO^ to -PO^). The remainder of the released energy appears as 

 heat. Oxidation of 1 mole (87 g) of pyruvate, proceeding via acetyl-CoA, contributes a total of 15 moles of ATP to the energy 

 pool. 



lA « Pyruvic decarboxylase; B = Malic enzyme; C = Transaminase ; D = CondeiiBlng enzyme; E = Aconitase; F * Isocltric dehydrogenase] 

 G = Oxalosueclnic carboxylase; H = ot-Ketoglutarlc dehydrogenase; I = Succinic dehydrogenase; J = Fumarase; K « Malic dehydrogenase; 



L » Oxalacetic decarboxylase 



Protein; 

 Carbohydrate; 



^ 



Protein: 

 Fat 



Pyruvate |^6.8. 12, 14_A. 



(C3H4O3) 



Protein 



V. 



Aspartate 

 (C4H7O4N) 



S 



Fumarate 

 (C4H4O,) 



Cis-aconitate 



Glutamate 

 (C5H9O4NI 



8, 14- 



/l/ Glucogenic amino acid precursors for pyruvate are: alanine, glycine, serine, threonine, methionine, cysteine, val i ne. /2/ Keto- 

 genlc amino add precursors for acetyl-CoA are: leucine, Isoleuclne, phenylalanine, tyrosine. /3/ Aspartic acid occurs as a com- 

 ponent of protein. /U/ Glutamic acid occurs as a conqjonent of protein or may be formed from: arginlne, proline, hydroxyproline, 

 hlstldine, ornithine. /5/ Coenzytt-A ( = ATP-pantoyl-p-alanyl-thloethanolamine) and d-lipoic acid required. /6/ In the oxidative 

 direction, DPN ( = dlphosphopyridlne nucleotide, a conqwund of nicotinamide, D-ribose, ^POi,, and adenine; also known as coenzyme I) 

 acts as hydrogen acceptor; in the reverse direction DPSHg is hydrogen donor. /?/ In the oxidative direction, TPN (= trlphosphoryrt- 

 dine nucleotide; coenzyne II) acts as hydrogen acceptor; In the reverse direction, TPNH2 is hydrogen donor. /8/ DPT (= dlphos- 

 phothiamlne; thiamine pyrophosphate; cocarboxylase ) required as coenzyme for the carboxylase (a); also Mg"*^, or Mn"*"*" Is required 

 ae activator for the enzyne. /9/ Blotln required as coenzyme for decarboxylation. /lO/ 2H enters into the reaction. /ll/ 2H 

 released and their electrons transferred to cytochrome. /12/ Hydrogen ions transferred to DPN (or. In the case of Isocitrate — ^ 

 oxalsucclnate, to TPN) and pass In turn to flavoproteln, cytochrome-c, cytochrome oxidase, and finally to combination with mo- 

 lecular oxygen. For each H thus passed and finally oxidized, 1.5 moles of ATP are formed by the addition of energized phosphate 

 ( --PO1+) to ADP. /15/ CO2 enters into the reaction. /ll*-/ COo released. /15/ HgO enters into the reaction. /16/ HgO released. 

 /I7/ NHi enters Into tae reaction by transamination. /18/ NHj transferred frcm glutamate by transamination, then enters 

 Into Krebs Cycle via succlnyl ^ CoA. /l9/ Footnotes 5, 6, 8, 12, U apply to this reaction. /20/ For details of cytochrome 

 system, see table 108. 



189 



