the rate of an elementary reaction is proportional to the product of the concentrations of the participating molecules.

ex. substrate, product, cofactor, enzyme

makes simultaneous but seperate operation and regulation of similar pathways possible.

allows coordination of pathways through regulation of transport of metabolites and coenzymes between cell compartments.

direct stimulation or inhibtion of the activity of critical enzyme.

it rapidly alters pathway activity.

these enzymes operate far from equilibrium and deteremine the flow of materials through a pathway called the flux.

enzymatic actiivty can be regulated through non-covalent interactions of enzymes with small molecules other than substrate.

allosertic binding occurs at sites seperate from the substrate binding site.

binding of allosteric regulators changes the rate of reaction.

binding of effectors is reversible, so response time can be instantaneous.

in reversible pathways (glycolysis and gluconeogensis), seperate enzymes are needed to run in opposite directions-controlled by allosteric.

isozymes are different enzymes that catalyze the same reaction

they share similar sequences

their regulation and kinetics are often different

1. muscles consume glucose to use it for energy production= capture glucose for its own use

hexokinase I, II, III

2. liver maintains blod glucose homeostasis by consuming or producing glucose, depending on prevailing blood glucose concentration

hexokinase IV

1. pyruvate can be converted into oxaolacetate to start gluconeogenesis

-glucose can be converted into glycogen(storage form)

2. pyruvate can be oxidized to acetyl Co-A for energy production via the citric cid cycle

(first enzyme in each path is regulated allosterically by acetyl Co-A)

negatively allosterically modulated (inhibited) by NADH, succinyl Co-A, citrate and ATP (indicating that an E sufficient metabolic state)

-stimulated by ADP

inhibited by high levels of ATP

stimulated by igh levels of ADP and Ca2+ (in muscle tissue, Ca2+ signals contraction and stimulates E yielding metabolism to replace the ATP consumed by contraction)

inhibited by succinyl Co-A ad NADH

stimulated by Ca2+

DNA first isolated (from WBC's by treating them with HCl to remove nuclei and then alkali to extract the contents of the nuclei).

found that nuclei contents were composed ot C, H, O, N and P (called all of this nuclein) -later called nucleic acid.

the basic subunit of nucleic acids is a nucleotide, which is composed of a nitrogenous base (pu or pyr) and one or more phosphate groups.

nitrogenous base

pentose sugar

phosphate (1 or more)

nitrogeneous base

pentose

synthesis takes place in the liver.

all nucleotides can be made up of CO2, NH3, amino acids, and 5C sugars

when you are trying to come up with a drug to counteract a specific agent, you want to kill off the microbes but not harm the patient.

when theres a pathway that we dont have or use, it is used as a really good target site because it is not used by the body so it cannot cause harm

catalyzes the reaction of carbamoyl phosphate and aspartate to yield carbamoyl aspartate (in the biosynthesis of pyr)

in bacteria:

it is also a key regulatory enzyme(catalyzes an early reaction in seqeunce)

-inhibited allosterically by CTP

-stimulated by ATP

catalyzes a reaction to yield carbamoyl phosphate in the biosynthesis of Pyr

in mammals:

it is the key regulatory enzyme (catalzyes an early reaction in sequence)

-inhibited by UTP (end product)

-stimulated by PU nucleotides (keeps balance)

a purine base without the sugar

important in nucliec acid breakdown

binds to bacterial DHF reductase nearly 100, 000x better than to mammalian enzyme (selective toxicity)

-used to treat certain urinary and middle ear bacterial infections

inhibitor of dihydrofolate (DHF) reductase (so cells cant make thymine)

-related to methotrxate and has similar mode of action

-used to treat cancer

bacteria are able to manufacture folate from constituent molecules one of which is PABA.

the first antibiotic discovered was sulfanilamide, which is an analog of PABA.

its effective because it inhibits bacterial growth but not growth in eukaryotic cells because they cant make folate anyway.

good selective toxicity inhibits/kills the microbe but little effect on the human host

two main functions

1. NADPH is used for biosynthetic reactions- therefore, PPP is very active in tissues that are involved in biosynthesis of fats, amino acids, and steroids (ex. adipose tissue, mammary glands, adrenal cortex and liver).

-in these tissues where large amounts of NADPH are needed, there is even an option that recycles the sugars back to G6P so that the pathway can be run again and more NADPH can be produced.

2. NADPH is also used to counter the damaging effects of oxygen radicals (via glutathione)

very important in detoxifying hydrogen peroxide

reduces H2O2 to water (H2O, but is oxidizes itself

to continue to function it must be reduced again by NADPH produced by the PPP

NOTE: ionizing respiration, sulfa drugs, herbicides and antimalarial drugs all increase the production of hydrogen peroxide and free radicals and thus increase reliance on the PPP to produce NADPH

caused by an elevated concentration of uric acid in the blood and tissues.

joints become inflamed, painful and arthritic due to abnormal deposition of sodium urate crystals.

common manisfestation is a sudden onset of painful arthritic pain.

excess uric acid may also deposit in kidneys and ureters as stones--> renal damage.

mostly in males

inhibits xanthine oxidase (which catalyzes the conversion of hypoxanthine to xanthine to uric acid)

used to cure GOUT

when xanthine oxidase is inhibited... the excreted products of purine metabolism are xanthine and hypoxanthine, which are more water-souldble and uric acid and less likely to for crystalline deposits

results from a severe HGPRT deficieny

indicaes how important the salvage pathways are

sexlinked=mostly in males

results in excessive uric acid production (uric acid is a purine degradation product)

symptoms= spasticity, mental retardation, highly aggresive and gout like symptoms

ADA catalyzes the conversion of adenosine to inosine

if the reaction is blocked, dAMP is salvaged by kinases to give high levels of dATP--> leads to an increased concentration of cell dATP

dATP is a strong inhibitor of ribonucleotide reductase

(ribonucleotide reductase catalyzes the reduction of ribonucleotides to deoxyribonucleotides

provided eviednce that DNA is the genetic material of life

used transformation of non-virulent to virulent strains of Streptococcus pneumoniae

provide definitive proofthat DNA is the genetic material of life

-used bacteriophage infection of bacterial cells and radiolabelled to prove that DNA, not protein, carried the  genetic information

watson and crick structure

right-handed double helix

10.5 base pairs per turn of helix

most common and most stable under physiological conditions

right-handed double helix

11 base pairs per turn --> helix is wider with deeper major groove and shallower minor grooves

favoured in solutions relatively devoid of water

(still debateable, only seen in labs so far)

left-handed helix

12 base pairs per turn --> slender, elongated helix

may play a role in regulating expression of some genes or in genetic recombination

close interactions between stacked bases in nucleic acid has the effect of decreasing its absorption of UV light relative to that of a solution with the same concentration of free nucleotides

-absorption is further decreased when two complementary nucleic acid strands are paired

 genotypic classification

- DNA form organism to be identified is extracted and exposed to species-specific molecular probes

genotypic classification

-probes used to localize specific nucleic acid sequences unique to agenus, species or subspecies and then sequences are amplified and sequenced to define precise identity

microfilaments

microtubules

intermediate filaments

function is is cell division, protein localizationa nd determination of cell shape

irregular shaped

80% mass of dsDNA (arranged either as circular, or single bacterial chromosome) +20% RNA and protein

not membrane bound

 a closed circular dsDNA molecule

(except vibrio cholerae and borrelia burgdorferi

looped and coiled extensively

nucleiod proteins aid in folding (different from histones)

small, closed, circular DNA molecules

exist and rpelicate independently of chromsome

relatively few genes present

genes on plasmid are not essential to host but may confer selective advatage (drug resistance or ability to use unusal nutrients)

CURINg is the loss of aplasmid

classificaiton of plasmids based on mode of existence, spread and function

complex structures consisting of proteina nd RNA in 2 subunits

sites of protein synthesis

often in chains or clusters

extremely numerous (~20 000 per bacterium)

smaller than eukaryotic ribosomes

separation of cell from envt

selectively permeable barrier

-prevents leakage of components out of cytoplasm

-GATE throughw hich nutrients, small molecules enter cells and through which wastes leace

-ransport systems aid in movement of molecules

location of crucial metabolic processes in PROKAYOTES

-proteins for biosynthetic reactions, generate energy, transport nutreints

detection of and response to chemicals in surroundings -aid of special receptors in membrane

found in prokaryotic membranes

because htey lack STEROLS

hopanoids are sterol like and aid in maintaing membrane stability and fluidity

only a few prokaryotes lack cell wall

provides shape to cell

protects cell from osmotic lysis

protects against toxic substances

contributes to pathogenicity

has peptidoglycan

produces symptoms of disease (fever)

site of action of antibiotics (penicillin)

different chemical composition... gram staining

meshlike polymer composed of identical subunits

two sugar derivatives and several different amino acids

sugar derivatives... N-actely glucosamine (NAG) and N-acetylmuramic acid (NAM)

amino acids - L-alanine, D-glutamic acid, meso diaminopimelic acid DAP and sometimes L-lysine

backbone has alternating NAG and NAM residues by covalent bonds --> high molecular weight

a peptide chain of four alternating D and L amino acids connected to carboxyl group of each NAM in glycan backbone

in GRAM POSITIVE CELL WALL

polymer of glycerol and ribitol joined by phsophates and connected to peptidoglycan

important virulence factors

-promote attachment to other bacteria and specific receptors on mamalian cell surfaces (adherence)

-may be shed (toic to host)

can be used to distingiush bacterial serotypes

lipotechioc acid is connected to PM lipid

in GRAM NEGATIVE CELL WALL

the area between external surface of cytoplasmic membrane and internal surface of outter membrane

contains peptidoglycan

-contains variety of hydrolytic enzymes for breakdown of large macromolecules for metabolism (proteases, lipases, collagenases) important for virulence factors

in GRAM NEGATIVE lipid bilayer with other molecules embedded in it (lipopolysaccarhide, lipoprotein, porin proteins)

aymmetric bilayer structure

--inner leafleft= phospholipids

--outer leaflet composed of LPS

-unique to gram negative bacteria

-also called endotoxin

three parts

1. lipid A- buried in outter membrane (primarily responsible for toxic effects pf LPS in host)

2. core polysaccarhide- joined to lipid A, projects form surface

3. O side chain (o antigen)- polysaccahride chain extending outward from core, contains peculiar sugars and varies in composition between bacterial strains