CHEMICAL ARCHITECTURE OF THE CENTRAL NERVOUS SYSTEM l8oi 



(Tr)-cysteine-(2r)-cysteine (H ISTIDINE ) 



I kiu _ r~ U _ ^ r\' 



table 4. Other Components oj Brain* 



HC— CH 



NH - CH - CO 



I 



C = CH 



HN N 



\ A. 2e 



H + 



2H* 



2H 



FIG. 7. Structural formula of the hemopcptide of cytochrome 

 C. The porphyrin nucleus is joined to the peptide chain by 

 thioether bonds between cysteine and the vinyl side chains of 

 the 2 and 4 positions on the pyrrole rings. R indicates amino 

 acids intervening between those named. The covalent bond 

 between the imidazole ring of histidine and the iron (Fe) of 

 the porphyrin nucleus is indicated by the broken arrow. The 

 suggested point of electron (<■) transfer is shown to the right 

 of the imidazole ring. Inset: Suggested structure of the cyto- 

 chrome C molecule (axial cross section view). The porphyrin 

 plate (P) is visualized as surrounded by helices (I!) of amino 

 acids. The solid circle represents the end-on \ iew of helix formed 

 from the hemopeptide chain with the two nitrogens A ' of the 

 histidine imidazole ring and the covalent bond to the porphyrin 

 iron (F). Three other peptide helices, as proposed, are also 

 viewed end-on, as indicated by broken circles, and one of these 

 is also thought to have a histidine element with similar covalent 

 bonding as indicated (53). 



(53) have elucidated much of the structure of this 

 enzyme-protein, as shown in figure 7. Cytochrome c 

 is a metalloprotein containing 0.43 per cent iron in a 

 porphyrin unit which is joined to the protein by 

 thioether bonds. The hemopeptide shown has been 

 isolated and its structure established, although the 12 

 amino acids vary somewhat from species to species. 

 The functional group is visualized as the imidazole 

 ring of histidine, joined by co-valent bonding to the 

 iron nucleus and accepting the electrons from previous 

 donors to pass them on through mediation of cyto- 

 chrome oxidase to join with oxygen as water. Ehren- 

 berg & Theorell (5:3) have determined that the 

 peptide chain exists in the form of an a-helix and 

 visualize the cytochrome-c molecule as formed of 

 four such helices enclosing the porphyrin plate, as 

 sketched in the figure. The molecule has a molecular 

 weight of about 12,000, comprising some hundred 

 amino acids and one porphyrin nucleus, with di- 



o 



mensions of the order of 25 X 25 X 40 A. Such a 



% dry wt. 



Acid soluble N: 



(', total N) 

 Amino N (,% acid sol. N) .. . 

 Acid soluble P: ', , dry wt. . 

 Inorganic P ('} acid sol. P) 



Ash: c / c dry wt 



Nucleic acids 



Gray 



1.6 



(.8) 

 (50) 

 0.9 



(25) 

 6.1 



White 



I .1 

 (.8) 



(30) 



0.85 



(25) 



4-2 



Whole Brain (jimole/gm) 



Glycogen 



Glucose 



I.actic acid 



Pyruvate 



Oxygen : 



cerebral go 



vascular 225 



ATP 4- ADP 

 Phosphocreatine 



Citrate 



a-Ketoglutarate 



Succinate 

 Fumaratc 

 Malate 

 Fatty acids 



Oxaloacetate . . . . 



DPN (as nicotina- 

 mide) 



Pyridoxinc 



Coenzyme A (as 

 pantothenair 



Riboflavin 



Cytochrome C (as 

 Fe).... 



Ammonia 



Free glutamate, as- 

 partate and deriv 



Serine 



Choline (free). . . . 



Ethanolamine (free 

 and phosphate i 



O.65 



0.2 

 O.06 



o. 1 



O.OI 



0.005 



0.16 



25 

 0.7 



trace 

 1.0-6.5 



* References : 46, 80, 91 , 94, 

 185, 213, 214, 218-220. 



95, 123-125, 127, 153, 163-166, 



molecule is, of course, not typical of protein molecules 

 of other types, but it provides an example of how 

 subunits of a protein may be aggregated. The helical 

 configuration has been proposed for other molecules, 

 notably nucleic acids (11, 184), so that this principle 

 of construction may lac rather general for proteins 

 and related molecules. 



other constitutents. Compared to the three 

 principal constituents of cerebral tissues, water, 

 lipids and proteins, the remaining compounds con- 

 stitute a small portion of the total (about 4 per cent 

 of the total mass, or 15 per cent of the total solids). 

 Some of these are listed in table 4. Most of the im- 

 portant substrates and metabolites of the brain are 

 present in trace amounts only. Even though the 

 oxygen content appears to be appreciable, this amount 

 at a normal rate of utilization by human brain would 

 last only about 10 sec. (125). Thus, the brain contains 

 no significant store of essential nutrients but depends 

 upon a continual supply from the cerebral circulation. 

 When this supply fails, destruction of cell framework 



