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