50-60% of body weight in adults,

more fat = less water (for obese ppl)

75% o body weight in kids

60% intracellular.

40% extra

-plasma, interstitial water

drink more = pee more.

-dipolar nature of water

-H bond = weak, noncovalent interaction

-H + more electronegative atom

-Each water mol can have 4 H bonds

(A) H interacts with

(B) O interacts

-bicarbonate and inorganic anions and cations

-Na- and Cl- in ECF

-K+ and phosphates in ICF

Principally by energy-requiring transporters that pump Na+ out o fcells in exchange for K+

Different compartments

water mov'ts

osmotic pressure to reach equilibrium

1.  acids donate a H+ to a solution, pH lower than 7

2.  Bases (OH-) accept Hydrogen ions

What is the [H+] of pure water?

What is the pH of pure water?

1. 10x-7 mol/L

2.  pH = 7

1. undissociated acid

'ic acid'

ie:  acetoacetic acid

ie:  lactic acid

2.  dissociated anionic component

'ate'

ie: acetoacetate

ie: lactate

Acids in the blood of a healthy individual

Example of a strong acid?

Acid:  Sulfuric Acid (H2SO4)

Anion:  Sulfate SO4-2

pKa = completely dissociated

Acids in the blood of a healthy individual

Example weak acid?

Weak acid:  Carbonic Acid (R-COOH)

Anion:  Bicarbonate (R-COO-)

pKa = 3.8

The greater is the tendency to dissociate a proton

pKa = -log Ka

[image]

If the pKa for a weak acid is known, this equation can be used to calculate the ratio of the unprotonated to the protonated form at any pH.

Calculation for pKa:

Salicylic acid, pKa = 3.4

(salicylic acid ↔ salicylate- + H+)

Blood pH = 7.4

Calculate ratio?

= a weak acid and its conjugate base

-can cause a solution to resist changes in pH when H ions or OH ions are added

An avg rate of metabolic activity produces a lot of acid per day.

-If all of this acid were dissolved at one time in unbuffered body fluids, their pH would be <1.

pH of blood?

Intracellular pH?

pH of blood:  7.36-7.44

Intracellular pH:  ~7.1

-Carbon

CH-: methyl, ethyl, propionyl, butyl, pentanyl

-branched 'iso-'

-double bonds 'ene'

aliphatic:  straight chain

aromatic:  ring

Bonds:  C-O, C-N, C-S, C-P

-determines the types of reactions

-alcohol, aldehyde, ketone, ester, amide

Carboxylic + alcohol?

Carbox + amide group?

1.  ester compound

2.  amine 

Oxidation:  loss of H+ atoms, gain of O atoms

Reduction:  gain of H+ atoms, loss of O atoms

Groups that carry a charge:

- and +

1.  acidic groups dissociate an anion with a - charge

2.  compounds within nitrogen are usually basic acquire a + charge

1.  anions formed by dissociation of acidic groups

2.  examples of amines

Polar bonds:  C-O, C-N

Sulfur can carry a slight partial neg charge

[image]

name me.

Two systems for identifying the carbon atoms in a compound. This compound is called 3-hydroxybutyrate or β-hydroxybutyrate. 

Carbohydrates:

What are monosaccharides?

1.  a linear chain of > or equal to 3 C

-one C=O, others C-OH

-general formular Cn H2n On

-suffix = 'ose'

C=O aldehyde = aldose

C=O ketone = ketose

-trioses, tetroses, pentoses, hexoses

Fructose name?

Glucose name?

1.  Ketohexose

[image]

2.  aldohexose

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Position of the hydroxyl group farthest from the carbonyl carbon.

D = right

L = left

D and L example:

glyceraldehyde

[image]

The C in the center of the D and L glyceraldehyde contains 4 different substituent groupd.  A different arrangement creates and isomer that is nonsuperimposabe mirror image.

D or L.  What are most sugars?

D or L.  What are AA's?

D- sugars

L- AA's

They have the same chemical formula but differ in the position of the hydroxyl group on one or more of their asymmetric C's.

[image]

Stereoisomers that differ in the position of the hydroxyl group at only one of their asymmetric C's.

[image]

D-glucose and D-galactose are epimers at position 4.  D mannose and D-glucose, position 2.

1.  C=O reacted with -OH

2.  a 5 or 6 membered ring

3.  -OH to O part of the ring and C=O to C-OH (anomeric C).

3a.  -OH down = alpha position

3b.  -OH up, beta position

3c.  interchange up and down = mutarotation

[image]

**Highlighted = anomeric C's

1.  Anomeric C-OH can react with -OH or -NH group of another compound to form glycosidic bond.

2.  the linkage may be either alpha or beta

3.  N-glycosidic bonds = nucleosides/tides

4.  O-glycosidic bonds = lactose

3-12 monosaccharides (glycoprotein)

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1.  Lipids

2.  •Aliphatic: CH-3@ one end (ω-carbon) & -COOH @ the other end.

1.  Chain length

2.  Unsaturation

1.  vegetable oil = unsaturated.  liquid at Rt

2.  Butter = saturated.  solids at RT

= a glycerol with one of more fatty acids attached through ester linkages.

-monoacylglycerols, diacylglycerols, triacylglycerols

[image]

= lecithin

-major phosphoacylglycerols found in the membranes

-Amine (+), phosphate (-):  amphipathic (both + and - charges in functional groups).

Phosphorylcholine group attached to ceramide

-cell membranes and myelin sheath

What are steroids?

-number of rings?

steroid nucleus:  four ring structure

**cholesterol is the steroid precursor in humans

-al of the steroid hormones are synthesized by modifications to the ring or C-20 side chain

= Amino Acids

1.  An amino + a carboxylic acid group

2.  In proteins, L-alpha AA's

= presence of nitrogen (amine) in the ring.

**except uracil (pyr)

Compounds that have a single electron, usually in an outer orbital.

-free radicals from eating BBQ!  Oxidizing H+ from overcooking meat etc.

1.  Nitrogen dioxide

2.  Smog

3.  Cigarette smoke

Lecture 2:

Topic 1:  Compartmentation in Cells

What are membranes?

Topic:  Plasma Membrane

What is the structure of the PM?

= a lipid bilayer with embedded proteins

-selectively restricts polar compounds

Integral:  span the cell membrane

Peripheral:  attached to the membrane surface, does not span the membrane.

Topic:  Proteins in the PM

What is the fxn of integral proteins?

-They are channels/transporters and receptors

-They are also structural proteins

-yes, by ionic solvents.  integral proteins are permanent.

-spectrin-actin skeleton (filaments) create this mesh.

1.  small polar compounds can pass by ion channels

-glu, K+ in

-Ca and NA out

Gases:  02 and CO2

Lipid soluble substances (steroid H)

Water diffuses randomly

Concentration gradient in:

1.  simple diffusion and facilitative diffusion

1.  Transmembrane proteins form a pore for ions

2.  Either open or closed in response to stimulus

3.  voltage-dependent calcium channel

and 

4.  •Ligand-gated CFTR (cystic fibrosis transmembrane conductance regulator) via phosphorylation

1.  Protein transporters (carriers)

2.  energy used

3.  Na+, K+, ATPase and Na⁺/Ca²⁺ exchanger (antiporter), Na-Glu symporter

Topic:  Vesicular Transport across the PM

What is phagocytosis?

1.  Eliminate unwanted materials and recycling (aa)

2.  destroy infectious bacteria and yeast

3.  provide normal turnover of cells and organelles

Endosomes and lysosomes?

Phagosomes and lysosomes?

Endosomes give rise to lysosome

Phagosomes fuse with lysosome

Topic:  Peroxisomes

What type of rxns happen in peroxisomes?

-oxidation rxns using molecular oxygen.

-specifically, oxidation of fatty acids, cholesterol to bile acids.

Topic:  Nucleus

What is the largest subcellular organelle?

Most of the genetic material,

-chromosomes, chromatin, DNA and histones (histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes.)

-rRNA transcription and processing

-ribosome assemly

Topic:  ER

-What is the ER composed of?

1.  synthesize lipids and steroids (via enzymes)

-triaclglycerols and phospholipids

2.  metabolize carbohydrates and steroids (but not lipids), and regulate calcium concentration

3.  drug metabolism

-cyt 450 oxidative enzymes metabolize drugs and toxic chemicals

4.  Glycogen is stored in sER in liver

1.  secreted from cell

2.  sequestered within lysosomes

3.  embedded in PM

1.  N-linked glyosylation (enzymatic process that attaches glycans to proteins, lipids, or other organic molecules)

2.  Addition of GPI anchors

1.  modifies the proteins made in the rER?

2.  Sort and distribute these proteins

Topic:  Cytoskeleton

What is the purpose of the cytoskeleton?

1.  structure

2.  shape of the cell surgace

3.  arrangement of subcellular organelles

1.  microtubules (tubulin)

2.  thin filaments (actin)

3.  intermediate filaments (keratin)

1.  all nucleated

2.  platelets in blood

Yes, via proteins kinesins (carrier move to PM) and dyneins (carrrier to move to the membrane).

-use atp to move

Topic:  Signaling molecules

Receptor types?  How many are there?

=4

1.  Ligand-gated ion channels, not much signaling pathway.  ligand binds to ion channels

2.  G-protein coupling receptors

3.  Tyrosine kinase coupling receptors (receptor with an intracellular segment with an enzyme fxn (ie:  kinase-  puts a phosphate on another protein)

4.  steroid receptors-  ligand goes into cytoplasm, binds to receptor inside and cell.  gets into nucleus and regulates transcription.

Growth, development, differentiation.

-Tend to be used a lot with cancer drugs-  regulate cell growth.  inhibit kinase receptors if they are too active.

1.  Phospholipase C pathway- involves GQ protein (a G protein):  So, if drug binds to a receptor, the receptor activates GQ protein-  thsi will activate a phospolipase C:  converts a phospolipid to diacyglycerol.

Activate protein kinase C. 

Other:

IP3 will mobilize calcium from ca storage inside the cells.  Calcium will activate protein kinase C.

1.  Alpha s (stimulates adenyl cyclase) , Alpha i (inhibits adenyl cyclase), Q (activates phospholipase C).

-accounts for the majority of G protein coupling receptor signaling.

If it deals with a receptor-  desensitization, desensitization of signal

Phosphotase- removes phosphate to terminate signal.

Phosphodiasterase-  enzyme that helps to reduce cAMP (2nd messenger made by adenyl cyclase).

Session 3-

Amino Acids and Proteins

Amino acids are composed of?

1.  Carboxyl group, -COOH

2.  Amino Group, -NH3

3.  1 of 20 side chains

1.  Alanine

2. Glycine

3.  Isoleucine

4. Methionine

5.  Phenylalanine

6.  Proline

7.  Tryptophan

8.  Valine

1.  Asparagine

2.  Cysteine

3.  Glutamine

4.  Serine

5.  Threonine

6.  Tyrosine

1.  Aspartic Acid

2.  Glutamic acid

1.  Arginine

2.  Histidine

3.  Lysine

1.  Metabolism:  Enzymes and polypeptide Hormones

2.  Movement:  Contractile proteins in muscle

3.  Bloodstream:  hemoglobin and albumin

4.  Immunoglobulins-  fight microbes

1.  Does not bind or give off protons or participate in H or ionic bonds.

2.  Promotes hydrophobic interactions

How are nonpolar AA's located in proteins?

1.  Protein in an aq solution (polar environment)

2.  In a hydrophobic environment (a membrane)

1. R of nonpolar AA tend to cluster together in interior of protein

2.  non-polar R groups are found on the outside surface of a protein, interacting with the lipid environment.

-differs from other AA in that proline's side chain and a-amino N form a rigid, 5 membered ring.

= has a secondary, rather than primary, amino group = Imino acid.

1.  fibrous structure (collagen)

2.  Interrupts a-helices in globular proteins.

1.  Can participate in H bonds

2.  Have an attachment site for phosphate group

3.  Have an attachment side for oligosaccharide

1.  Can participate in H-bonds

2.  Have an attachment site for oligosaccharides (amides)

A buffer is a molecule that resists changes in pH (by donating or accepting protons).  

-AA's can do this if they are free standing.

= proton donors.

-at physiologic pH, fully ionized (- charge)

= accept protons

-at pH 7.4, fully ionized (+ charge)

-It is weakly basic, but its side chain can be either positively charged or neutral depending on the ionic environment.

-Role in hemoglobin.

What are a few optical properties of AA's?

1.  alpha C of each amino is chiral (except for GLYCINE).

2.  AA's have an optically active C atom.

3.  AA's can exist in 2 forms, D and L.

[image]

1.  contain weakly acidic alpha carobxyl groups

2.  contain weakly basic alpha amino groups.

Topic:  Titration of an AA

pI = average pK1 and pK2 for AA's with 2 pKa's-  2 H's to give away

For charged AA's with 3 H's to give away, average the 2 closest in nature.

1.  Bicarbonate as a buffer

2.  Drug absorbtion

Primary:  The sequence of AA

Secondary:  Regular arrangements of AA's located near to each other in primary structure

Tertiary:  The 3 dimensional shape of the folded chain

Quaternary:  The arrangement of multiple polypeptide subunits in the protein.

[image]

1.  Linear sequence of AA

2.  Joined covalently by peptide bonds

3.  amide linkages between the alpha-carboxyl group of 1 AA and the alpa amino group of another.

[image]

1.  The most common helix

2.  A spiral structure, 3.6 AA's/turn

3.  side chains point toward the outsides

[image]

1.  keratins

2.  fibrous proteins

3.  myoglobin

-Proline

-Charged AA's-  glu, asp, his, lys, arg

-AA's with bulky side chains- trp

-all of the peptide bond components are involved in H bonding.

=antiparallel to each other, N and C terminals alternate.

=parallel to each other 

[image]

What is 'random coil'?

Topic:  Supersecondary Structures (motifs)

How are globular proteins constructed

1.  Composed of alpha helix, beta sheet, nonrepetetive sequences, beta bends

2.  motifs are usually produced by packing side chains from adjacent secondary structural elements close to each other.

= functional and 3D structural units of polypeptides.

(>200 AA in length generally consist of 2 or more domains)

AA interactions stabalizing tertiary structure.

1.  Disulfide bonds

A covalent linkage (-SH) of each of 2 cysteine residues to produce a cysteine residue.

ie:  immunoglobulins, albumins

nonpolar side chains tend to be located in the interior of the polypeptide molecule

[image]

(-COO-) aspartate or glutamate interact with (-NH3+) lysine

[image]

-controlled by interactions between side chains of AA's

-occurs within seconds to minutres

-employs a shortcut via all folding possibilities

-Use all 4 types of interactions

Topic:  Quaternary Proteins

What are monomeric proteins?

Consist of a single polypeptide chain.

-The arrangement of these polypeptide subunits is called the quaternary structure of the protein.

noncovalent interaction, H bonds, ionic bonds and hydrophobic interactions

[image]

= a group of specialized proteins

-heme (iron as a prosthetic group-  prosthetic group = something is needed for protein to function) acts as a tightly bound prosthetic group

-4 N keep the iron in place.

Mutation on beta chain on heme changing from charged Glu to nonpolar Val.

-why sickle cells?  they get caught in the microvasculature.  can't fit through the capillaries.  clogging of the pipes.

1.  cytochrome P450-  drug metabolism

2.  cytochrome C

3.  catalase:  gets rid of hydrogen peroxide

4.  myoglobin-  single unit of O2

5.  Hemoglobin

1.  T form-  deoxy form (TAUT) = tense

-low oxygen affinity

2.  R form- O2 bound, relaxed form

-high 02 affinity

[image]

allosteric because 4 different subunits cooperatively working together.

-Hb reversibly binds oxygen

-allosteric, other site, effectors

-pO2, pH, pC02, and 2,3 bisphosphoglycerate.

The release of 02 from Hb is enhanced when the pH is lowered (change affinity of Hb to 02).

-OR, when the Hb is in the presence of an increased partial pressure of CO2.

[image]

-2,3-BPG:  the most abundant organic phosphate in RBC.

-2,3 BPG:  synthesized from an intermediate of the glycolytic pathway.

-Decreases O2 affinity of Hb by binding to deoxyHb.

-Reduces affinity, enables Hb to release O2 (stabalizes T form).