v = [Vmax * S]/ [ [S] + Km]

V = V max = kcat [E]

Independent of substrate concentrations

kcat/Km

(example - triose phosphate isomerase)

Proline and glycine - proline has 5 membered ring 

Glycine is highly flexible so you don't want it in helix

Will usually connect successive of strands of antiparallel B sheets 

Typically involves 4 amino acids, usually proline and glycine - glycine has no side chain - little steric hindrance

H bond between 1st and 4th amino acid 

Also called motifs

example) EF hand (helix loop helix found in calcium binding proteins)

Primary structure of protein 

Will assume lowest energy structure 

pKa

Higher pKa ... weaker acid 

Taut --> Oxygen breaks hydrogen bonds --> Relaxed --> CO2/positive charge --> induce formation of interchain and intrachain salt bridges --> release of oxygen and back to taut

First 6 weeks: zeta and epsilon genes are upregulated

6 weeks: lifelong expression of alpha and begin gamma

birth: beta and some delta

Any major change that causes leftward shift - erythrocytosis

Any major change that causes rightward shift - anemia 

Methemoglobinemia - Fe2+ altered to Fe3+ and is unable to bind oxygen

Any remaining normal hemoglobin has increased affinity - leftward shift 

moderately severe hemolytic anemia

3 alpha chains defective 

ALAS II (erythroid) - high iron stimulates mRNA translation

ALAS II (hepatic) - high heme will increase mRNA degradation

Low levels of PLP decrease ALAS activity 

Requires zinc 

Also called ALA dehydratase

Requires 2 molecules of ALA 

Inhibited by lead 

Most severe in urban areas

GI + neurobehavioral symptoms

Hypochromic microcytic anemia (less hemoglobin because less heme being made) 

5 mcg/dl <

Most preventable environmental disease among children less than 6 years of age 

Will see more nervous system effects like in AIP (ALA synthase, hydroxymethylbilane synthase)

HMB synthase enzyme activity reduced - nervous system pathology 

block in uroporphyrinogen decarboxylase 

Most common porphyria 

Decreased activity of uroporphyrinogen decarboxylase due to mutations in UROD 

Photosensitivity and discolored urine (red to tea color, and pink under fluorescence) are seen

Hyperbilirubinemia

further separates double stranded DNA

ATP will get hydrolyzed 

Initiation of DNA replication

Primase activity

Synthesizes first 20 nucleotides

No proofreading

Immediately after DNA synthesis

Mut S and Mut L join (Mut H does strand specificity by methylated sequences) 

Mut H has endonuclease activity - nicks strand, and then exonuclease removes dNMPs

Resynthesis carried out by DNA polymerase

Acts at any cell cycle stage, not just after DNA replication

DNA glycosylase will cleave modified base - number of glycosylases 

Removed by AP endonuclease and exonuclease

DNA polymerase beta fills in gap

Can repair almost all bulky lesions - large multiprotein complex scans DNA for distortions in DNA structure, rather than specific base change

Exinuclease will bind and cleave damaged DNA at both sides of the lesion 

Rare, autosomal recessive disorder by bad homologous recombination

Poor motor skills, poor balance (ataxia), immunodeficiency, acute sensitivity to ionizing radiation

binds to b subunit of RNA polymerase - preventing chain extension 

Used in TB treatment

Binds to DNA template, interfering with RNA pol movement

Occasionally used in cancer chemotherapy

TF2D: binds TATA box + other promoter elements

TF2F: brings RNA Pol II to promoter

TF2H: melts DNA and allows pol 2 to clear the promoter