1

Phospholipid structure

Amphipathic molecule (phosphatidyl choline)hydrophobic part: fatty acidshydrophilic part: phosphate & choline

2

Membrane structure

3

Membrane components

4

Transmembrane proteins

5

Intercellular structures

Desmosomes

“spot welds”, dense proteins (cytoplasm & intercellular) fibers (intermediate filaments) extend across cells

epithelial cells (especially skin), cardiac intercalated disks

Tight junctions

cell “collar”, block large molecules, no lateral protein movement

epithelial cells

Gap junctions

cell-cell communication, small molecules (<1000 MWt)cardiac intercalated disks, smooth muscle

6

Desmosomes

fig 3-10a

“spot welds”, dense proteins (cytoplasm & intercellular)

fibers (intermediate filaments) extend across cells

epithelial cells (especially skin), cardiac intercalated disks

7

Tight junctions

fig 3-10b

cell “collar”, block large molecules, no lateral protein movement

epithelial tissue (esp. kidney, gut)

paracellular pathwaybetween cells

8

Gap junctions

fig 3-10d

cell-cell communication, small molecules (<1000 MWt)

cardiac intercalated disks, smooth muscle

9

Epithelial cell

fig 3-10c

10

Protein ligand interaction

Proteins could be: Ligands would be:

enzymes substrates, allosteric regulators

receptors chemical messengers

transporters transported substances

transcription factors transcription regulators

any of above drugs

11

Protein-ligand binding properties

Specificity:binding depends on ligand size, shape, charge

Affinity:strength of binding: i.e. [ligand] at 50% binding

Saturation:there is a finite number of binding sites

Competition:structurally similar molecules can compete for binding

12

Specificity

binding depends on ligand size, shape, charge

fig 3-26 fig 3-27

13

Specificity

protein Y specificity

greater than

protein X specificity

fig 3-28

14

Affinity

strength of binding: i.e. [ligand] at 50% binding

fig 3-29

15

Affinity & saturation

strength of binding: i.e. [ligand] at 50% binding

fig 3-30

16

Affinity (different proteins)

strength of binding: i.e. [ligand] at 50% binding

fig 3-31

17

Affinity (different ligands)

strength of binding: i.e. [ligand] at 50% binding

18

Protein-ligand binding properties

Specificity:binding depends on ligand size, shape, charge

Affinity:strength of binding: i.e. [ligand] at 50% binding

Saturation:there is a finite number of binding sites

Competition:structurally similar molecules can compete for binding

and remember:the protein can be an enzyme, receptor, transporter, etc.

19

Regulating binding site properties

a. Allosteric modulationreversible binding at another (“allo-”)

sitecan be activation or inhibition

20

Regulating binding site properties

a. Covalent modulationchemical alteration of the proteincan be activation or inhibition

21

Metabolism (pathways)

22

Metabolism (key)

Key:A: glycogenesis, B: glycogenolysis, C: glycolysis, C+D: anaerobic

glycolysis (lactic acid fermentation), E: gluconeogenesis, F: irreversible step (pyruvate dehydrogenase), G: protein synthesis, H: proteolysis, I: lipogenesis, J: lipolysis, K: Krebs cycle, L: urea synthesis, M: ketogenesis

Anabolic pathways: A, G, I

Catabolic pathways: B, C, E, F, H, J, K

Liver only: E, L, M

Mitochondrial: K

Ribosomal: G

Smooth endoplasmic reticulum: I

23

Energy content