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core metabolic pathways
glycolysis, gluconeogenesis, fatty acid metabolism, citric acid cycle, oxidative phosphorylation
glycolysis
degrades glucose into 2 pyruvate molecules and 2 ATP
gluconeogenesis
process of synthesizing glucose
fatty acid metabolism
synthesis converts acetyl-CoA to malonyl-CoA, while degradation (beta oxidation) breaks down fatty acids into acetyl-CoA
oxidative phosphorylation
couples the oxidation of the coenzymes to phosphorylate ADP, creating ATP
metabolism common intermediates
pyruvate, acetyl-CoA
citric acid cycle
oxidizes acetyl-CoA into CO2+H2O, producing reduced NADH+FADH2
acetyl-CoA
central degradation product of glucose, fatty acids, and ketogenic amino acids. it can be oxidized for energy or used to synthesize fatty acids and ketone bodies
pyruvate
end product of glycolysis and degradation of glucogenic amino acids. it can be converted into acetyl-CoA, used in gluconeogenesis, or used for amino acid synthesis
hormonal control of tissues
insulin, glucagon, epinephrine
glucagon
has no effect on muscles, increases triglyceride hydrolysis in adipose tissue, and increases glyconeogenesis as well as gluconeogenesis in the liver
insulin
increases glucose uptake and glycogen synthesis in muscles, increases glucose uptake and fatty acid synthesis in adipose tissue, and increases glycogen/fatty acid synthesis while decreasing gluconeogenesis in the liver
epinephrine
increases glyconeogenesis in muscles, increases triglyceride hydrolysis in adipose tissue, and increases glyconeogenesis and gluconeogenesis in the liver
function of carbohydrate
provide energy, supply carbon for cellular components, store chemical energy (as glycogen), and serve as structural components
carbohydrate isomerism
they exist as mirror images/enantiomers, designamted as D/right or L/left based on orientation of the -OH group on the chiral carbon furthest from the carbonyl group.
what do humans mainly metabolize
D-glucose
monosaccharides
simplest sugars classified by carbon count, 3-triose, 4-tetrose, 5-pentose, 6-hexose. they are further categorized as aldoses/aldehyde group or ketoses (ketone group)
cyclization
monosaccharides form stable cyclic structures, pyranose=6-membered, furanose=5-membered. the new chiral center is the anomeric carbon, the alpha form has the -OH pointing down, while the beta from has it pointing up
key sugars
fructose, glucose, galactose, ribose/deoxyribose
glucose
most important sugar for metabolism
galactose
found in lactose, differs from glucose at carbon #4
fructose
sweetest common sugar and major ketohexose
ribose/deoxyribose
use in DNA and RNA
disaccharides
2 units linked by glycosidic linkage
examples of disaccharides
maltose, lactose, sugar
polysaccharides
long chains of glucose units. starch, glycogen, cellulose
starch
polysaccharide; energy storage in plants
glycogen
polysaccharide; energy storage in animal liver and muscles
cellulose
polysaccharide; structural component of plant cell walls, people are unable to digest it, but it serves as a dietary fiber
lipids
hydrophobic molecules used for energy storage and structures, they are split into saponifiable and nonsaponifiable
saponifiable
contain esters and can by hydrolyzed
nonsaponifiable
can’t be hydrolyzed
fatty acids
long-chain carboxylic acids the form micelles in water, unsaturated fatty acids and essential fatty acids
unsaturated fatty acids
contain double bond, usually cis, creating kinks that lower their melting points, making them liquids (oils) at room temperature
essential fatty acid
linoleic and linolenic acid must be obtained from the diet
triglycerides
storage forms of fats and oil, they undergo hydrolysis (via lipases) or saponification (witha base to make soap)
hydrogenation
converts liquids oils into solids fats but can produce unhealthy trans fatty acids
membrane lipids
include phosphoglycerides, sphingomyelins, and cholesterol. these form a bilayer where unsaturated chains increase membrane fluidity
cholesterol
precursor for bile salts, sex hormones, and vitamin D
hormones
cortisol increases glucose/glycogen and acts as an anti-imflammatory. aldosterone regulates ion and water balance
prostaglandins
regulate reproduction, blood clotting, and inflammation
what do most drugs target?
proteins (enzymes or receptors)
binding affinity
measured by the dissociation constant (Kd); a lower Kd indicates a stronger interaction
potency
measured by IC50 (50% inhibition) or EC50 (50% biological response)
IC50
represents the concentration of a drug or substance required to achieve 50% inhibition of a target's activity, used when a drug is designed to block or reduce the function of a specific protein, such as an enzyme or receptor
EC50
refers to the concentration of a ligand (drug) needed to elicit 50% of a biological response, measures the concentration required to reach half of the maximum possible effect or response
drug disposition (ADME)
absorption, distribution, metabolism, excretion
lipinski’s rules
predict poor oral absorption a drug has: molecular weight >500g/mol, more than 5 H-bond donors, more than 10 H-bond acceptors, a partition coefficient (membrane solubility) > 5
drug discovery
identify a target, develop an assay, and deter structure-activity relationship (SAR)
Preclinical
testing in animals for pharmacokinetics (PK) safety and toxicity before FDA approval for human trials
clinical trial - phase 1
small group of healthy volunteers; checks for safety and tolerability
clinical trial - phase 2
small group of patients; tests for efficacy and dosage
clinical trial - phase 3
large scale trials (1,000+ patients) for statistical significance and economic analysis
clinical trial - phase 4
post marketing surveillance to find rare or long-term side effects
commercial reality
drug development is high risk; only about 1 in 50 projects reach the market; patents typically last 20 years, after which generic competitors can enter the market