Biomolecules

Pitch of alpha helix

5.4A

Residues between hydrogen bonds

4

Coil diameter of hydrogen bond

5A

Secondary structure

Spatial arrangement of amino acids near eachother in linear sequence

Tertiary structure

Spatial arrangment of amino acids far apart from eachother in primary sequence

Quaternary structure

Spatial arrangement in protein resulting from polypeptide subunit aggregation

Pauling and grey

Beta pleated sheet

Beta pleated sheets

H bonds stabilise it, residues fully extended, can be antiparallel

Distance of beta pleated sheets

3.5

Antiparallel beta pleated sheets

Goes round

Beta turn

4 residues, glycine 3rd, maintains tight structure

Collagen

3 intertwined helical polymers, steric hindrance means glycine interior

Length and diameter of collagen

3000A, 15A

Keratin

Heptad of 7 residues, 2 intertwined alpha-helices

HIV RT action 1

Viral ss+RNA copied to ss-DNA

HIV rt action 2

Ss-DNA copied to dsDNA

HIV rt action 3

dsDNA trasncribed to viral mRNA

HIV rt action 4

Viral mRNA to ss+RNA

Stages of glycolysis

Investment (3) , cleavage (2) and harvesting (5)

Reactions of investment stage

3

Glycolysis reaction 1 action

Glucose -> glucose-6-phosphate

Glycolysis reaction 1 enzyme

Hexokinase

Glycolysis reaction 1

Irreversible, requires energy from ATP

Glycolysis reaction 2 action

Glucose-6-phosphate -> fructose-6-phosphate

Glycolysis reaction 2 enzyme

Phosphoglucoseisomerase

Glycolysis reaction 2

Reverse, Isomerisation

Glycolysis reaction 3 action

Fructose-6-phosphate -> fructose-6-bisphosphate

Glycolysis reaction 3 enzyme

Phosphofructokinase

Glycolysis reaction 3

Reversible, hydroxy group phosphorylated

Glycolysis reaction 4 action

Fructose-6-bisphosphate to DHAP and GAP

DHAP

Dihydroxyacellate phosphate

GAP

Glyceraldehyde-3-phosphate

Glycolysis reaction 4 enzyme

Aldolase

Glycolysis reaction 5 action

DHAP to GAP

Glycolysis reaction 5 enzyme

Triose phophateisomerase

Glycolysis reaction 6 action

GAP to bisphophoglycerate

Glycolysis reaction 6 enzyme

Glyceraldehyde-3-phosphate dehydrogenase

Glycolysis reaction 6

Dehydrogenation, coupled to phosphorylation, NAD+ reduced

Glycolysis reaction 7 action

Bisphosphoglycerate to 3-phosphglycerate

Glycolysis reaction 7 enzyme

Phosphoglycerate kinase

Glycolysis reaction 7

Anhydride bond hydrolysed, generates ATP

Glycolysis reaction 8 action

3-phosphoglycerate to 2-phosphoglycerate

Glycolysis reaction 8 enzyme

Phosphoglycerate mutase

Glycolysis reaction 8

Phosphate shifts from c3 to c2

Glycolysis reaction 9 action

2-phosphoglycerate to phosphoenolpyruvate

Glycolysis reaction 9 enzyme

Enolase

Glycolysis reaction 9

Dehydration reaction

Glycolysis reaction 10 action

Phosphoenolpyruvate to enolic pyruvate

Glycolysis reaction 10 enzyme

Pyruvate kinase

Glycolysis reaction 10

Irreversible hydrolysis reaction

...

Glucose

Pyruvate

Enolic pyruvate

cac reaction 1 action

acetyl co A + oxaloacetate = citrate

cac reaction 1 enzyme

citrate synthase

cac reaction 1

citryl coA intermediate, enzyme initally can only bind to oxaloacetate

cac reaction 2 action

citrate to isocitrate

cac reaction 2 enzyme

aconitase

cac reaction 2

cis-aconitase intermediate, enzyme has 4Fe, 4S with 3 cysteines

cac reaction 3 action

isocitrate to alpha-ketoglutamate

cac reaction 3 enzymes

isocitrate dehydrogenase

cac reaction 3

produce first pair of high energy electrons, oxidative decarboxylation

cac reaction 4 action

alpha-ketoglutarate to succinyl coA

cac reaction 4 enzyme

alpha-ketoglutarate dehydrogenase complex

cac reaction 4

produces 2nd pair of high energy electrons

cac reaction 5 action

succinyl coA to succinate

cac reaction 5 enzyme

succinyl coA synthetase

cac reaction 5

succinyl coA thioester cleaved, coA displaced by orthophosphate to succinyl phorsphate, phophoryl group removed by His, phosphohistidine transfers P to GDP

cac reacton 6 action

succinate to fumarate

cac reactoon 6 enzyme

succinate dehydrogenase

cac reaction 6

3rd pair of electrons accepted by FAD on histidine

cac reaction 7 action

fumurate to malate

cac reaction 7 enzyme

fumurase

cac reaction 7

hydration reaction

cac reaction 8 action

malate to oxaloacetate

cac reaction 8 enzyme

malate dehydrogenase

cac reaction 8

produces 4th pair of electrons, positive deltaG so driven by fact its product is used by citrate synthase

Step 1 of ethanol fermentation

pyruvate decaroxylase and thiamine pyrophosphate coenzyme convert pyruvate to acetaldehyde

Step 2 of ethanol fermentation

alcohol dehydrogenase reduces it to ethanol, regenerating ATP

Citric acid cycle

further oxidation of organic compounds that yields ATP, ending with complete oxidation to CO2

Oxaloacetate

Citrate

Coenzyme A

Myosin structure

light meromyosin and heavy meromyosin (S1 heads and S2)

Myosin

Track is actin, used in muscle

ATP binding to myosin

decreased affinity for actin

Kinesisn

Track is microtubules, used for transport

Dyneins

Large heavy chain, used in cilia and flagella

ATP binding for kinesin

increased affinity for microtubules

SFT step 1

tropomyosin blocks myosin binding site at rest

SFT step 2

nerve impulse increase calcium ion concentration

SFT step 3

troponin C binds to calcium, conformational change so myosin head can bind

Troponin I

binds actin to complex, preventing contraction in calcium absence

Troponin T

binds to tropomyosin

Head structure

actin binding site, P-loop, nucleotide binding site, regulatory and essential light chain

Step 1 myosin movement

ADP->ATP releases myosin

Step 2 myosin movement

ATP rearranges lever arm

Step 3 myosin movement

ATP->ADP enables myosin to bind to actin

Step 4 myosin movement

phosphate release increases strength of binding, allowing level rest (power stroke)

Actin structure

G actin combines to make F actin, a helical rope structure

Kinesin structure

two heads with extended stalk, head based on P-loop NTPase, light chains bind to carboxyl terminal

Action of kinesin

operate in tandem

Step 1 kinesin movement

ADP bound kinesin binds to mictotubule, ADP disassociates

Step 2 kinesin movement

ATP binds and causes neck linker to zip onto core and 2nd head thrown forward

Step 3 kinesin movement

2nd head binds, 1st hydrolyses and unzips neck linker, 2nd binds to ATP, zips up and 1st thrown forward

Dynein

has microtubules as track, two homologous SOKDA subunits (alpha and beta tubulin), produce helical array, bundle is called axoneme, 9 MT pairs and 2 singlets

P-loop NTPase

proteins that convert ATP into kinetic energy

track

steers the motion of motor assembly

affinity for filament track.....

enables bind, pull and release

Lock and key

Emil Fischer 1890

Induced fit model

Daniel Koshland

Catalytic group

Amino acid chain that makes/breaks bonds

Saturation effect

At constant enzyme concentration, reaction rate increases with substrate until Vmax is reached

Vmax

Maximum velocity or rate at which an enzyme is catalyses a reaction

Enzymes

Biological catalysts that function by stabilising transition states in reactions

Km

Substrate concentration where V0 is equal to 1/2 Vmax

Michaelis-Menten model

Describes kinetic property of enzyme, concentration of enzyne is constant

Michaelis-Menton model equation

E+S=ES=E+P

Michaelis-Menten equation

v = (vmax [S])/(Km + [S])

Michaelis-Menten equation 2

Km = (K-1 + K2)/K1

Lineweaver-burk plot

Plot of 1/V0 against 1/[S] used to calculate Km (gradient) + Vmax (y-intercept)

Uncompetitive inhibitor

Vmax and Km lower

Non-competitive inhibitor

Vmax reduced, Km same

Competitive inhibitor

Increases Km, Vmax same

Post-translational modification types

Ubiquitination, Sumoylation, Hydroxylation, Phosphorylation, Lipidation, Acetylation, Glycosylation

Acetylation

involves acetylation of N-terminal amino acids using acetyl coA and N-acetyl transferase enzymes

Acetylation of lysine in histone

Histones more negative so less attracted to negative phosphate group, loose coil, transcriptionally active

Sumoxylation

Addition of small ubiquitin like modifiers, involving activation, conjugation and ligation

Ubiquitination

Addition of ubiquitin protein to substrate protein, make up of 76 a.as, monoubiquitin K29, involves activation, conjugation and ligation

Lipidation

Covalent modification of proteins with lipids, reversible, can be enzymatic with farnesyl transferase and palmoitoyl transferase

Glycosylation

Attachment of sugar moelcule to residue, can be O linked or N linked

O-glycosylation

Attachment of sugar to O group of threonine and serine, no characteristic sequence

N-glycosylation

Attachment of carbohydrate to asparagine residue, sequeunce N-X-S/T except when X is proline

Oligosaccharide of N-glycosylation

3 glucose, 9 mannose, 2 glucosamine

Hydroxylation

Addition of OH group to residue only proline and lysine, present in collagen

Phosphorylation

Attachment of phosphate group to OH group in side chains

Kinases

Attach phosphate group to OH group

Phosphatases

Remove phosphate group to OH groups

Monosaccharides

Glucose, fructose, galactose

Disaccharides

Sucrose, maltose, lactose

Homopolysaccharides

Used for storage (alpha-glycosidic linkage, helical) and structure (beta-glycosidic linkage, linear)

Cellulose

Beta-1-4 glycosidic linkage, linear, insoluble, layers

Chitin

Beta-1-4 glycosidic linkages, N-acetylglucosamine, long straight chain

Amylopectin starch

Branched, homopolymer, alpha-1-4 ad alpha 1-6 glycosidic linkages, soluble

Amylose starch

Straight chain, alpha-1-4 glycosidic linkages, have maltose, unbranched, spiral shape, chair

Glycogen

Branched, spairingy soluble, forms colloidal solutions, alpha-1-4 glycosidic linkages, branches alpha-1-6 bonds, shorter branches

Heteropolysaccharides

Glycosaminoglycans and glycoproteins

Glycoproteins

Shorter, branched oligosaccharide covalently attached to protein backbone

Glycosaminoglycans

Repeating sequence of 2 monosaccharides, associated with protein non-covalently, form proteoglycans or mucopolysaccharides

Examples of glycosaminoglycans

Chondrotin, keratin, heparin, dermatan sulfate, hyaluronate

Heparin

Sum of total chemical processes occuring that result in growth, energy production and waste removal

Two metabolic activities

Capture and conversion of energy, transformation of organic compounds into others

Chemotroph

Obtain energy by breaking down organic compounds

Anabolism

Biosynthesis of macromolecules, requires energy input, not spontaneous so use enzyme catalysts or couple it to favourable reactions

Catabolism

Biosynthesis, motility, transport and waste, break down molecules, produces energy, spontaneous, increases entropy

Types of metabolic reactions

Ligation, Isomeration, group transfer, oxidation/reduction, hydrolytic reactions and addition/removal of functional groups

Ligation (metabolic)

Form bonds by using free energy from ATP cleavage

Isomerisation

Rearrangement of bonds within a molecule

Group transfer

Movement of phosphate groups etc

Oxidation/reduction

Donation/accepting protons in carbon compounds

Hydrolytic

Bonds cleaved with the addition of water

Addition/removal of functional groups

Forms double bonds e.g. lyases

Metabolism regulation

Amount of enzyme, catalytic activity (inhibition) and substrate accessibility (compartmentalism)

Activated carriers

phosphoryl transfer drives unfavourable reactions, alter proton and protein activity

NAD

Nicotinamide adenine dinucleotide

FAD

Flavin adenine dinucleotide

Kc=

([C]x[D]y)/([A]p[B]q)

If Kc known

Position of equilibrium predicted in closed system

Causes of spontaneous reactions (first law)

Reactions that give out energy, products are of low energy

Causes of spontaneous reactions (second law)

Reactions increase disorder (entropy)

Gibbs free energy equation

DeltaG = deltaH - TdeltaS

High temperature

DeltaG -ve, deltaH +ve, deltaS +ve

Low temperature

DeltaG -ve, deltaH -ve, deltaS -ve

Spontaneous

DeltaG -ve, deltaH -ve, deltaS +ve

Creatine phosphate action

CP + ADP -> ATP + creatine

Formation of ATP

Glyceraldehyde-3-phosphate -> 1-3-bisphosphoglycerate -> 3-phosphoglycerate acid

Endosome-lysosome pathway

Small, stable, non-specific, cysteine serine and aspartic proteases

Endosome-lysosome protease action

Secreted by lysosome -> recognised by phosphotransferase -> N-acetylglucosamine-1-phosphate to mannose residue -> glucosaminidase removes glucosamine (m6P)

Ubiquitin-proteosome pathway

Multidomain, specific, tagrets those marked by ubiquitin, requires ATP, 4 7-membered rings with a cap region and alpha and beta subunit

Serine proteases

Acyl enzyme intermediate, chymotrypsin (aromatic side chain), trypsin (positive lysine/arginine)

Metalloproteases

Zinc, carboxypeptidases, matric MPS used in tissue modelling, cell signalling and growth factors, lysosomal

Cysteine proteases

Involves cysteine-sulfhydryl group, his residue deprotonates cysteine which is then nucleophilically attacked, thioester intermediate

Cysteine proteases example

papain, cathepsin, caspases, calpains (cleave intracellular proteins)

Activation of caspases

cleaved to remove inhibitory sequence or disassociates, activated by apoptosomes