Biochemistry – Lecture 25 – Flashcards

oligosaccharides

is an antibiotic produced by a strain of Streptomyces erythreus

erythromycin

1. Erthryomycin binds to the 50s subunit of the bacterial 70s rRNA complex, and protein synthesis and subsequently structure/function processes critical for life or replication are inhibited. 2. Erythromycin is an antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma (a genus of bacteria without a cell wall) and Legionellosis (stains poorly with Gram stain because of unique lipopolysaccharide coat, requires silver staining to visualize) 3. Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting are very common

Erythromycin

Erythromycin

50s subunit of the bacterial 70s rRNA complex

a genus of bacteria without a cell wall

Legionellosis

It's a gram negative bacteria, and you need to stain with silver to visualize it.

Legionella bacteria

1. It's a disease caused by Legionellosis bacteria that causes illness, pneumonia, rapid breathing then chest pain. Can cause death 2. First recognized outbreak occurred on July 27, 1976 at the Bellevue Stratford Hotel in Philadelphia, where members of the American Legion, a United States military veterans association, had gathered for the American bicentennial. Within two days of the event's start, veterans began falling ill with a then unidentified pneumonia. They had rapid breathing and complained of chest pain. As many as 221 people were given medical treatment, and 34 deaths occurred. At the time, the U.S. was debating the risk of a possible swine flu epidemic, and this incident prompted the passage of a national swine flu vaccination program. That cause was ruled out, and research continued for months, and various theories proposed - from toxic chemicals to terrorism aimed at the veterans. U.S CDCP mounted an unprecedented investigation and by September ended up focusing on the hotel environment itself and found in January 1977 the true cause, the Legionellosis bacterium. It was finally identified and isolated, and was found to be breeding in the cooling tower of the hotel's air conditioning system, which then spread it through the entire building. This prompted new regulations worldwide for climate control systems. 3. Identified in January 1977. 4. Have to do a silver stain

1. is a glycopeptide antibiotic used in the treatment of infections caused by Gram positive bacteria 2. Vancomycin acts by inhibiting proper cell wall synthesis in GRAM POSITIVE bacteria. Due to different mechanism by which gram negative bacteria produce their cell walls and the various factors related to entering the outer membrane of Gram-negative organisms. Vancomycin is not active against Gram-negative bacteria. 3. Vancomycin prevents incorporation of N-acetylmuramic acid (NAM) and N-acetylglucosamine peptide subunits into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. Basically, it ruins the base of everything 4. Vancomycin is a ****ing huge hydrophilic molecule that's able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG peptides. This binding of vancomycin to the D-alanyl-D-alanine prevents the incorporation of the NAM/NAG subunits into the peptidoglycan matrix.

Vancomycin has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of vancomycin resistant organisms means that it is increasingly being displaced from this role by new antibiotics. Vancomycin never became first-line treatment for Staphylococcus aureus for several reasons... in other slides

Vancomycin acts by inhibiting proper cell wall synthesis in GRAM POSITIVE bacteria. Due to different mechanism by which gram negative bacteria produce their cell walls and the various factors related to entering the outer membrane of Gram-negative organisms. Vancomycin is not active against Gram-negative bacteria.

Vancomycin is a ****ing huge hydrophilic molecule that's able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG peptides. This binding of vancomycin to the D-alanyl-D-alanine prevents the incorporation of the NAM/NAG subunits into the peptidoglycan matrix.

Vancomycin

1. Poor oral bioavailability: not well absorbed into GI tract, have to give intravenously. 2. Other orally available antibiotics including methicillin (and its successors, nafcillin and cloxacillin) have better activity against staph aureus. Vancomycin is still used for methicillin resistant staph aureus.

methicillin, nafcillin, cloxacillin

It's a cooler version of starch and glycogen, where the main linkages aren't alpha(1,4), but they are alpha(1,6). This isn't amylopectin, where 1,4 is main linkage with occasional 1,6 here and there. No, dextrans are linked 1,6 and have occasional 1,4 1,3 and 1,2 linking adjacent strands

dextrans

1. Dextrans formed by bacteria are components of dental plaque 2. Dextrans in plaque presumably provide protection for oral bacteria 3. Cross linked dextrans are used as "Sephadex" gels in column chromatography 4. These gels, used to separate biomolecules on the basis of size, are up to 98% water.

dextrans

protection for oral bacteria

cross-linked dextrans

Sephadex gels made from cross linked dextrans.

alternating D-galactose and 3,6-anhydro-L-galactose

agarose gels (sephadex another answer)

The tertiary structure of agarose is a double helix with a so-called threefold screw axis. The central cavity of this double helix can accommodate H2O molecules. Agarose and agaropectin readily form gels that contain high amounts of H2O (up to 99.5%).

Glycosaminoglycans

proteoglycans

linear chains of repeating disaccharides in which one unit is an amino sugar and one or both is negatively charged.

glycosaminoglycans

1. Linear chains of repeating disaccharides in which one unit is an amino sugar and one or both is negatively charged 2. Heparin, very high negative charge, is natural anticoagulant. 3. Hyaluronates (up to 25,000 disaccharides units) are components of the vitreous humor of the eye and of synovial fluid, the lubricant fluid of the body's joints. 4. Chondroitins and keratan sulfate are found in tendons, cartilage, and other connective tissue 5. Dermatan sulfate is a component of the extracellular matrix of skin 6. Glycosaminoglycans are constituents of proteoglycans

heparin

Glycosaminoglycan structure consisting of up to 25,00 disaccharide units. Component of the vitreous humor of the eye and of synovial fluid, the lubricant fluid of the body's joints.

Hyaluronates

glycosaminoglycan structure found in tendons, cartilage, and other connective tissue

Chondroitins and keratan sulfate

glycosaminoglycan component of the extracellular matrix of skin.

dermatan sulfate

Proteoglycans, heparin, hyaluronates, chondroitins, keratan sulfate, dermatan sulfate

animal cell surfaces

You have GAG units with tetrapeptide bridges?

These polysaccharide structures, glycoproteins and proteoglycans, regulate cell-cell recognition and interaction. The uniqueness of the "information" in these structures is determined by the enzymes that synthesize these polysaccharides

Cell surface polysaccharides/glycoproteins/proteoglycans

Proteoglycans are glycoproteins whose carbohydrates are mostly glycosaminoglycans. Proteoglycans are components of the cell membrane and the glycocalyx - the sugar shell around the cell. Proteoglycans typically consist of proteins with one or two types of glycosaminoglycans

Proteoglycans are glycoproteins whose carbohydrates are mostly glycosaminoglycans.

They are components of the cell membrane and the GLYCOCALYX - "sugar shell" around the cell.

Proteoglycan "sugar shell" around the cell

glycocalyx

proteoglycans

The cartilage matrix proteoglycan is highly hydrated. Compression of cartilage (as in walking) squeezes water out of the cartilage tissue to cushion the joint. Water is reabsorbed when the stress and compression diminishes.

1. Modulation of cell growth processes - proteoglycans bind growth factor proteins in the glycocalyx, providing a reservoir of growth factors at the cell surface 2. Cushioning in joints - Cartilage matrix proteoglycans absorb large amounts of water. During joint movement, cartilage is compressed, expelling water.

compressed

proteoglycans

Glycosaminoglycan structure with very high negative charge, - Natural anticoagulant - inhibits cell proliferation in a process involving internalization of the GAG moiety and its migration to cell nucleus.

highly sulfated, injectable

Heparin

heparin

anticoagulant, does not break down clots that have already formed, it allows body's natural clot lysis mechanisms to work normally to break down clots that have formed.

Heparin binds to enzyme inhibitor antithrombin III(AT), this causes a conformation change that activates AT through an increase in the flexibility of its reactive site loop. The activated AT then inactivates thrombin and other proteases involved in blood clotting. So, basically Heparin binds and activates AT, and AT inactivates thrombin and other proteases involved in blood clotting.

Enzyme inhibitor antithrombin III (AT)

activated by heparin, and inactivates thrombin and other proteases involved in blood clotting.

Lectins

proteins that bind carbohydrates with high specificity and high affinity.

Sugars are the "letters" of the sugar code. Lectins are "translators" of the sugar code. Many processes, such as cell migration, cell-cell interactions, immune responses, and blood clotting, depend on information transfer using this code.

the sugar code - sugars are the letters, lectins are the translators.

1. A protein (lectin) that is found in the blood, the levels of which rise in response to inflammation. 2. C-reactive protein (CRP) functions to limit tissue damage, acute inflammation, and autoimmune reactions 3. CRP acts by binding to phosphocholine moieties expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system, a system that helps clear pathogens from the body. 4 CRP is a diagnostic marker of inflammation, and as such it is an indicator of heart disease risk. Since many things can cause elevated CRP, it's not a specific prognostic indicator.

C-reactive protein (CRP)

CRP levels rise dramatically during inflammatory processes occurring in the body. CRP binds to phosphocholine on FOREIGN CELLS/MICROBES and DEAD/DAMAGED CELLS and is thought to assist in complement binding by enhancing phagocytosis by macrophages, which express a receptor for CRP.

Macrophages.

macrophages - target CRP bound to foreign/dead stuff

CRP

50,000

CRP

determining disease progress or the effectiveness of treatments