the building blocks of proteins

can be put together in many arangements whose proteins play many roles

there are more than 300 but only 20 are coded for in genetics and are common

backbone is carbon with an amino and a COOH

each has a distinct attached R group with properities that determine the amino acid's role in the protein

the partial positive on the oxygen and negative on the nitrogen can interact

divided based on R group properities

polar (uncharged (no net charge but can have a partial charge), acidic, basic)

non polar

most have N and C in their R group except for two non polar amino acids

tend to be in the interior of proteins when in a aquous enivorment to make the protein more stable

when embedded in a membrane the nonpolar amino acids will be exposed on the surface to interact with the non polar fatty acids in the interior of the membrane

tryptophan which has and H group but has 9 C still making it insoluable

methionine has a S group but it does not participate in H bonding or ionic bonding in our cases so it is non polar

non polar

isoleucine, leucine, valine

have branched chain R groups

the catabolism of these amino acids requires a common pathway that when interrupted causes maple suryp urine disease (MSUD)

maple surpy urine disease

caused by a defect in the pathway that breaks down branched chain amino acids

urine has a distinctive odor due to build up of these amino acids

neurotoxicity is caused by build up in the blood

mental retardation

if treated with a special diet in time symptoms can be avoided

in normal catabolism phenylaline is converted to tyrosine

when defective this causes phenylketonuria (PKU)

causes neurotoxicity due to build up of phenylalanine in the blood

mental retardation

can be treated with a special diet and symptoms avoided if caught in time

aspertame is broken down into phenyaline fyi

smallest amino acid due to smallest R group

is a major part of collagen which has the structure (GLY-X-Y)n

mutations can cause ostrogenesis imperfecta

because glycine is small if it is mutated and replaced by anything else it will cause issues

glycine is important in collagen so mutations can cause multiple bone fractures and normally death in utero

R group is bonded with the amino acid main structure

structure is then rigid around the alpha C, one conformation only

it has special structural roles ex: collagen

if put where it isnt suposed to be it can cause problems due to the rigidity

methyl group donor in methlyation reactions due to the methyl on the end of its sulfur group

polar or non polar but it is group in non polar because for our porposes it does not participate like the other polar amino acids do

have uncharged, acidic, or basic R groups

R groups can participate in hyrogen or ionic bonds

allowing reaction with eachother, aqueous enivornments, exposed protein surfaces, enzyme/substrate

ASP and GLU

net negative charge at physiological pH

LYS and ARG

net positive charge at physiological pH

HIS is also included but at physiological pH its R group is mostly uncharged so the net +1 is not used in calculations but it can carry a charge in specific situations

SER, THR, TYR

hydroxyl group and be phosphorlyated in the presence of proteins

can turn on an off enzymes or participate in signal transduction

two CYS residues can interact to make a disulfide bond strenghtening the structure overall

oxidation reaction

can be N or O linked to the amide group of an ASN (N linked) or the hydroxyl of a SER or THR (O linked)

can attach to oligosacchrides and glycoproteins

important in cell surface recognition, antigens, extracellular matrix and mucins

dependent on glycocidic bond

protective glycoproteins in the digestive tract

precursor for synthesis of catecholamines including dopamine, epinepherine, and norepinephrine

function as neurotrasmitters in the brain or as hormone regulators of carbs and lipid metabolism

the first three are common to almost all proteins

1: primary

2: secondary

3: tertiary

4: quaternary: only applies to proteins with more than one polypeptide chain

the sequence of amino acids

this sequence is defined by a gene

have distinctive begining and end sequences that cannot be reversed and still perform the same function in biology it starts with the amine and ends with the COOH

alpha helix

beta sheet

commonly involve hydrogen bonding of polar peptide bonds

secondary structure

possible because peptide bonds are polar

the oxygen has a negative charge that can H+ bond with the partial positive of the amide hydrogen on a nearby pepride bond

this makes a helix where the R groups are facing outwards from the core of the chains

because R groups are rather close a stretch of amino acids with bulky or charged R groups of the same polarity can interfere with formation

proline is too rigid for the alpha helix and causes kinks

secondary structure

possible because of the polar peptide bond

H+ bonds are created by strings of peptides that fold back on eachother

not coiled tight

hydrogen bonds are perpendicular to the peptide bonds in the backbone

final three dimensional shape of a single polypeptide

R group of the amino acids interact to stabilize the structure

there are 4 main interactions

disulfide bonds

hydrophobic interactions

hydrogen bonds

ionic bonds

disulfide bonds are made by oxidation between two cysteine residues in a chain

this covalent bond adds lots of stability to the protein

only covalent bond in proteins outside the primary sequence

the partial positive on hydrogen bound to O or N can bind to negative charges or partial negatives on other atoms like O from a carboxyl or the carbonyl O in a peptide bond

H can also bind with surrounding water

only when there is more than one polypeptide chain

interactions between chains include hydrophobic, hydrogen bonds, and ionic bonds

ex: hemoglobin has 4 polypeptides; 2 alpha chains and two beta chains

Arginine Arg R

Histidine His H

Lysine Lys K

Serine Ser S

Threonine Thr T

Asparagine Asn N

Glutamine Glu Q

Tyrosine Tyr Y

Cysteine Cys C

alanine Ala A

Valine Val V

isoleucine Ile I

Leucine Leu L

Methionine Met M

Phenylalanine Phe F

Tryptophan Trp W

Glycine Gly G

Proline Pro P

tyrosine

(what is it the precursor to?)

do not encode an aa

UGA, UAA, UAG

u go away, u are away, u are gone

AUG (methionine) only

starts all protein synthesis

DOES code for the amino acid. AUG is the ONLY codon for methionine.

there could be an AUG down stream but it wont start anything

adding / subtracting nucleotides from a coding region

can cause a frameshift mutation

if it is a multiple of three added / subtracted and amino acid is completely deleted or added and the frame isnt shifted, no trunkation

trinucleotide repeat expansion mutation

it expands the protein

in coding region: cause protein product to be longer than normal and unstable

disease often shows anticipation in pedigree

point mutation

effects beta^s-globin gene (s for sickle cell effected)

normal code: GAG --> glatamic acid (-)

mutant code: GTG --> valine (neutral)

nonsense and frame shift mutation

phenylalanine hydroxylase gene: converts phenylalanine to tyrosine

>400 mutations possible

phenylalanine metabolites accumulate

retardation

 oral phenylalanine and tyrosine

deletion mutation

70% of the time it is 3 base pairs in the coding region of the cystic fibrosis transfer gene

phenylalanine is missing

protein is functional in the membrane but it does not get put on the membrane right so it does not function

splice site mutation

deficiency in alpha or beta-globin of Hb

trinucleotide repeat in a 5' non coding region

FMR-1 gene

retardation, long face, everted ears, large mandible, macro-orchidism (large testicles)

less protein is made, feedback methlyates the gene and stops its mRNA production

trinucleotide repeat in the 3' non coding region

protein kinase gene effected (signal transduction)

muscles contract but do not relax

shuts off the gene

what mutation is huntingtons disease? what does it effect?

when is ir diagnosed?

trinucleotide repeat in the coding region

repeat of glutamine codon causes the huntington protein to be unstable and aggergate

nerve cells die, proressive neuro degeneration

diagnosed between age 30-50

aa carboxyl group is covalently bonded to the hydroxyl on the 3' teminus of the tRNA (ester bond)

pyrophosphate is cleaved to two molecules of inorganic phosphate cleaving two high energy bonds

charging tRNA: 2 high energy bonds from ATP

binding aminoacyl-tRNA to A site: 1 GTP

movement of the ribosome to the next codon: 1 GTP

total 4

tRNA can recognise more than one codon for a specific amino acid

the third nucleotide of a codon and the 4th nucleotide of an anticodon can bindin non traditional ways allowing a tRNA to recognise more than one codon

aka polyribosome

multiple ribosomes can be on one mRNA to speed things up and protect the mRNA

aka pribnow box

consensus sequence of 6 nucleotides

10 nucleotides upstream

aka rifamycin

binds to prokaryotic RNA polymerase and prevents transcription

treats TB

in eukaryotes

transcribes precursors to rRNA in the nucleolus

eukaryotic

transcribes tRNA precursors

same in prokaryotes and eukaryotes

3 rRNA are transcribed as a single large precursor by RNA polymerase 1 in the nucleolus, indivigual rRNAs are cleaved out by RNAases, in eukaryotes the 4th rRNA is transcribed by RNA polymerase 3 then it does: intron loop removed, trim the 5' and 3' ends, base modifications, add 3' CCA

3' terminus contains a polyadenylation signal, poly a polymerase adds a stretch of adenine residues

signal for transport out of the nucleus, protects mRNA from nucleases

not encoded in the gene, the signal sequences is the A's are not

eukaryote

aka splicing

snRNPs made of snRnas and proteins combined with primary transcript from splicesome splice the introns

autoimmune disease

aantibodies to snRNPs and nucleic acids

tested by antinuclear antibody panel

butterfly rash

death cap mushroom

genus amanita

mushroom that accounts for 95% of mushroom deaths

alpha amanitin binds to RNA polymerase 2 inhibiting mRNA synthesis

leads to liver failure

~80 nucleotides

covalently linked to an amino acid on 3'

clover shape

interchain pairing

has a T in it

methlyated bases

Hydrogen bonds break but phosphodiester bonds dont

heat, alkali, chemicals

creates ssDNA

ex: norflaxciin, ciproflaxcin

inhibits topoisomerase II and DNA Gyrase

histone 1

 between nucleosomes condensing DNA into nucleofilament

prokaryotic

bind to single strands to prevent reanneling and protect DNA from nuclease degradtion because single standed DNA is mroe volurnable

prokaryotic

move towards the double stranded region of DNA, towards the replication fork, and forces the strands apart, SSB comes behind it and binds the strands

this can cause supercoiling

stop supercoiling

type 1 and 2

a special type 2 topoisomerase

introduces supercoils

inhibited by quinolones

important for seperation of the circular chromosomes after replication

condenses bacterial chromosomes and seperates two chromosomes once dna replication is complete

polymerases catalize synthesis 5' to 3'

the template is read 3' to 5'

DNA polymerase needs a free 3' -OH to begin synthesis, primase is an RNA polymerase that does not need the free -OH to begin synthesis so it copies the first 10 nucleotides to prime synthesis then DNA polyermase picks up on the new free -OH.

it also starts all the fragments on the laggins strand

enzyme in prokaryotes that elongates both the leading and lagging strand and has proofreading activities making sure it is base paired with the template

it is an exonuclease and degrades nucleic acids from the end working 3' to 5'

it does 5' to 3' polymerase activity and 3' to 5' exonuclease activity and 5' to 3' exonuclease activity

it removes the RNA primer (5-3 exo), replaces rNTP with dNTP (5-3 poly), profreads and corrects (3-5 exo)

eukaryotic DNA polymerase

contains primase and DNA polymerase (begins strand synthesis)

 eukaryotic DNA polymerase

DNA polymerase and proofreading (extends strands)

simillar to polymerase III

3' to 5' exonuclease activity

it extends to the ends of the linear chromosome

it contains a segment of RNA that is complimentary to the telomere releat and extends beyond the repeat it acts as a template for the polymerase because the real template the DNA fragment is longer than the template

it also hase reverse transcriptase activity

it copies its own template (RNA) into DNA extending the 3' over hang on the chromosome

this process is repeated

the overhang is filled by the action of primase and DNA polymerases

there will always be a section of DNA left single stranded

this 3' area assumes a special structure with the dsDNA and certian proteins to protect the end of the DNA

not in all cells

only in cells that continously divide and are not terminally diferentiated

chromosomes shorten and only live a finite number of divisions

some cells can activate the telomerase when it isnt needed and cause cancer

DNA copied into RNA

ex: telomerase

common strategy in viruses ex: HIV

lacks proofreading activvity, high mutation rate in viruses

strand directed mis matched repair

endonucleases nick damaged strand

some proteins remove damaged regions

excision endonuclease

excinuclease

cuts DNA on both sides of the damage and removes it

gap is filled by repair DNA polymerase (poly 1 in prokaryotes)

rare genetic disorder

results from deficiency in excision endonuclease

have to avoid sunlight, high risk of skin cancer

-CO-O-CO-

high energy bond

-CO-O-C-

condensation of COOH and oH

links fatty acid to glycerol

-CO-

in sugars and ketone bodies

-C-SH

in cysteine

-COOH

in fatty acids

2xHO-PO-O-C-

in nucleic acids

acetoacetate + HADH + H -->3-hydroxybuterate + NAD+

or

acetoacetate --> acetone + CO2

present in diabetes

shown by acetone in breath

redox reaction, intermediates in glucose metabolism, end products of glycolysis

pyruvate + NADH + H --> lactate

and

lactate + NAD -- lactic acid DH --> NADH + H + pyruvate

2 phosphoanhydride bonds

1 phosphomonoester bonds

1 glycocidic bond

2 -OH groups

C / (O+N) =

1-3 very soluble, 3-6 soluble, >6 insoluble

the outer P from ATP is transferred to the hydroxyl another molecule making a phosphromonoester bond

catalized by kinases

the phosphate is removed by hydrolizing the bond by phosphotase

tells the amount an acid will dissociate

=([CB][H+])/[acid]

most effective at +-1 from pKa of WA

more effective if more concentrated aka buffer capacity