Biology 216 - Lect 3 (Metabolism)
Objectives: Gross metabolism relevant to Med Bact      
Note: Text too much detail
I. Growth requirements of pathogens
   A. Chemoorganoheterotrophs - chemical bond energy; 
	reducing equiv from organic; carbon non-CO2

TABLE

	Photo	Chemo
Litho	Green Sulfur Bact	Nitrifying
Organo	Purple Non-sulfur	Pathogens

   B. Nitrogen - few can fix N2 (ex Klebsiella); May get N by 
	toxins which damage tissue - necrosis.
	N2 ---> NH3 (energy expensive)
   C. Inorganic ions - Mg, Mn, S, Fe
        Fe - Ability to acquire plays a central role in pathogenesis
	Restricted as Fe3+ in nature (insoluble ferric)
	Restricted in host by transferrin (systemic) and
		 lactoferrin (secretions)
	Host responds to infection by sequestering iron
		 (Decrease saturation of transferrin)
	Siderophores - 	small iron chelating compounds (siderophore 
		   receptor on bact surface/Outer membrane)
		Sid- mutants less virulent 
		(how were these isolated? EGTA media)
	N. mening uses Fe-transferrin cell receptor;	
	Others - citrate
	Iron regulation of dipth toxin transcription
	 (and certain other toxins)
   D. Temperature - most pathogens at body temp
	(37 C - we use 35 C)
         Exceptions - M. leprae (33 C - found on extremities/ 
	internal immune complexes)
	Yersinia enterocolitica - 30 C (37 in vivo) - Montana 
		outbreak found by leave plate out.
   E. Oxygen requirements
         1. Aerobes - require O2 as terminal e- acceptor of respiration. 
 	M. tuberc - apical regions of lung
         2. Facultative - both
         3. Strict anaerobe - cannot survive or grow in O2; 
	Require special transport and growth in lab.
	a. Pathogens in areas low in O2 - ischemic, necrotic,
		facultative (ex. fuso/actino gum disease)
	b. Unable to detoxify O2 products (O2-, H2O2 - super oxide 
		dismutase, catalase/peroxidase)
		O2-    ------> H2O2by SOD
		H2O2 -----> 1/2 O2 + H2O by Catalase
		 (Heme as cofactor, lactics don't produce heme)
		H2O2 -----> 2 H2O
II. Catabolism - breakdown reduced molecule (sugar, AA..) 
	in discrete steps and trap as ATP
    Pathways are unique and helpful in ID - Ex. Microscan, Biolog (H-acceptor)
    (Walk through HANDOUT)
	Glucose (686 Kcal) ----------------------> 6 CO2 (0 Kcal)	
	(respiration - final e-acceptor inorganic)
	Glucose (686 Kcal) ----------------------> CHO (Kcal discarded)	
	(fermentation)
	Polysaccharides (starch, maltose, lactose.....)		
	Monosaccharides (xylose, dulcitol.......)
	Glucose (central sugar)
	2 ATP by substrate level phosphorylation
	2 NADH ------------- 2 NAD (recycled)
	Pyruvate --------------> Organic end product (e-acceptor)
	Krebs (TCA) - sugars completely oxidized to CO2 ---> 
		NADH, FADH, ATP
	Electron transport (inner cell membrane) -> pH gradient -> 
		oxidative phosphorylation
	Final acceptor inorganic (O2 = aerobic respiration; 
		Non-O2 = anaerobic respiration)
    A. Sugars
    B. Fermentation pathway - homolactic, propionic, 
	2,3 butanediol, mixed acid...
    C. Respiration - O2, NO3 (anaerobic by Nitr Red), 
	cytochrome oxidase (phenylene diamine -> indophenol red)
    D. Generation of ATP
	Substrate level phosphorylation 
		(ATP from glycolysis and Krebs)
	Oxidative phosphorylation (ATP from pH gradient 
		across a membrane)
III. Summary - know general metabolism, where lab tests fit in.