Lecture 2 — Review of Biomolecules

>90% of the body’s mass consists of

• O

• C

• H

<10% of the body’s mass consists of

• Essential elements

• Many in ionic forms

• Major

  • Na+, K+, Ca2+, Mg2+, H+

  • Cl-, HCO3-, (PO4)2-, (SO4)2-

• Minor

  • Fe, I, Cu, Zn

Organic molecules contain

• Carbon

Biomolecules are

• Organic molecules that are essential for living organisms

Biomolecules examples

• Carbohydrates

• Nucleotides, Nucleosides, and Nucleic acids

• Lipids

• Proteins

Biomolecules functions

• Used as energy and building blocks

Inorganic molecules

• Salts, minerals, water

Carbohydrate general formula

• Cn H2n On

• Glucose C6H12O6

• Ribose C5H10O5

Most carbohydrates are

• Hydrophilic

• Very abundant in nature

• Used for structure and energy

• Many proteins and lipids are modified by the addition of carbohydrates

Nucleic acids

• (DNA, RNA)

• Function in information storage and transmission

Nucleotides consist of

• One or more phosphate groups

• 5-carbon sugar

• Nitrogenous base

Nitrogenous bases

• Purines

  • Adenine + Guanine

• Pyrimidines

  • Cytosine, Thymine, Uracil

Nucleosides

• Nucleotides minus a phosphate group

• Adenosine, Guanosine, Cytidine, Thymidine, Uridine

Cyclic AMP (cAMP)

• Like Cyclic GMP (cGMP)

• Important signalling molecule within cells

Cyclic GMP (cGMP)

• Like Cyclic AMP (cAMP)

• Important signalling molecule within cells

Lipids consist of

• C,H,O but different ratios than carbohydrates

• May also contain N and P

Lipid roles

• Hydrophobic

• Structure of cells (cell membrane)

  • Waterproof

  • Pliable

• Energy source

• Communication (within cells and between cells)

Lipid are a diverse group of molecules

• Fatty acids

• Glycerides

• Phospholipids and Sphingolipids

• Oxylipins (Eicosanoids)

Fatty Acid Structure

• Long unbranched hydrocarbon chain with 8-28 carbons

• Has carboxyl (acidic) functional group -COOH

• Saturated and Unsaturated types

• The more more double bonds, the less likely the fat is to be soluble at room temp

Saturated fatty acids charcteristics

• No double bonds — form a straight chain

Unsaturated fatty acids characteristics

• Double bonds — have a kink

• More double bonds leads to less solubility at room temp

Glycerides

• A derivative of fatty acids via dehydration synthesis

• Glycerol binds to a Fatty Acid

Glyceride formation

• Glycerol gives up H atom from hydroxyl group

• H combines with the OH of the fatty acid’s carboxyl group

• Forms water (H2O)

Monoglyceride

• Glycerol + 1 fatty acid

Diglyceride

• Glycerol + 2 fatty acids

Triglyceride

• Glycerol + 3 fatty acids

• Important form of stored energy in the body (adipose/fat tissue)

Phospholipids

• Derivative of glycerides

• “Diglyceride” with a phosphate group and variable R group

Amphipathic molecules

• Have both hydrophilic and hydrophobic regions

• Polar heads (Phosphate + R-group)

• Non-polar fatty acid tails

Phospholipid organization

• Can arrange themselves into bilayers, micelles, and liposomes

• Polar heads face ECF or ICF, non-polar tails towards each other

Sphingolipids, Glycophospholipids, Glycosphingolipids

• Modified phospholipids

Sphingolipids

• Incorporate a sphingosine molecules instead of glycerol and have only 1 fatty acid

• Forms lipid rafts on cell membranes that may help to protect the cell surface

Glycophospholipids

• A phospholipid with a carbohydrate group attached (usually a polysaccharide)

Glycosphingolipids

• A sphingolipid with a carbohydrate group attached

What modified lipids can be involved in cell recognition and signalling

• Glycosphinoglipids and Glycophospholipids

Steroids

• Basic structure consists of:

  • THREE 6-carbon rings

  • ONE 5-carbon ring

  • 17 C total

• Many derived from cholesterol

• Different R-groups give steroids their different functions

• Play roles in communication (hormones) and cell structure

  • Cholesterol

  • Cortisol

  • Testosterone + Estrogen

Oxylipins

• Derived by the oxidization of polyunsaturated fatty acids

Eicosanoids

• Are polyunsaturated fatty acids with a length of 20 carbons attached to a complete or partial carbon ring

Oxylipins and Eicosanoids function

• Many derived from arachidonic acid or other unsaturated fatty acids

• Synthesized as needed — not stored

• Function in communication within and between cells

• Prostaglandins

• Thromboxane

Prostaglandins

• Help mediate inflammation and pain response during injury/infection among other roles

Thromboxane

• Important for blood clotting (specifically platelet aggregation)

Proteins consist of

• C, H, O. N (and sometimes S)

Proteins

• Macromolecules

• Made of amino acids

Amino acids

• Are the building blocks of proteins

Amino acid structure

• Carboxyl group (-COOH)

• Amino group (-NH2)

• R-group (functional group)

R-group

• Determines the structure of the amino acid

• Therefore function

Peptide bonds

• The amino group of one amino acid joins the carboxyl group of the other with the loss of water

Peptides

• Short chains of amino acids

Oligopeptides

• Oligo — just a few

• Just a few amino acids

• 2-9 amino acids

Polypeptides

• 10-100 amino acids

Proteins

• Long chains of amino acids (>100 AA)

Structures of peptides and proteins

• Primary

• Secondary

• Tertiary

• Quarternary

Primary Structure

• A sequence of amino acids

Secondary strucrure

• Hydrogen bonds between adjacent amino acid chains or loops within the same chain create b-sheets and a-helices respectively

Tertiary structure

• A-helices and b-sheets combine to form globular or fibrous proteins

• Globular proteins

• Fibrous proteins

Globular proteins

• Usually soluble in water

Fibrous proteins

• Usually insoluble in water

Quarternary

• Multiple tertiary structures combine to form the finished protein

Proteins are what in cells?

• The tools of cells

• Proteins are versatile and carry out many different jobs

• 10,000-15,000 different types of proteins expressed

7 categories of soluble protein

• Enzymes

• Membrane Receptors

• Signal Molecules

• Membrane Receptors

• Binding proteins

• Regulatory proteins

• Immunoglobulins

Enzyme

• Control reactions inside cell

• Catalyzes biochemical reactions

Membrane Transporters

• Protein channels, carriers

Signal molecules

• Ligands

• Peptide hormones e.g. insulin

• Molecules that binds to something else

Membrane Receptors

• Bind specific ligands for cellular response

Binding proteins

• Found mostly in ICF

• Hemoglobin

Regulatory proteins

• Transcription factors

• Muscle contraction — tropomyosin

Immunoglobins

• Found in ECF

• IgG antibody

Protein Interactions

• Proteins must interact with or bind to other proteins, molecules, or ions

• Binding take place at the binding site on the protein

Properties of the binding site

• Specificity

• Affinity

Specificity

• The binding can only bind to specific ligands

Affinity

• Refers to the strength of the binding between protein and ligand

• High Affinity — will not let it go, strong

• Low Affinity — will let go, weak

Ligands

• Molecules that binds to protein binding sites

• Naturally present in the body — are endogenous ligands

Non-endogenous ligands

• Enter the body from the external environment and include drugs/toxins

Agonist

• A ligand that binds to a proteins binding site and alters the state of the protein resulting in a biological response

Antagonist

• A ligand that reduces the action of an agonist

• May also be called inhibitors, blockers

Competitive

• Bind to the same binding site as the agonist

• Causes biological response

Allosteric

• Bind to a different site than the agonist, but this interaction inactivates the binding site

• Changes the shape

Isoforms

• Closely related proteins — function is similar but affinity for ligands differs

Activation

• Proteolytic activation

• Cofactors

  • Ions

  • Small organic functional groups

Chemical Modulators

• Bind reversibly or irreversibly to proteins and alter their binding affinity or activity

Competitive binding

• Bind to active site (site of normal ligand), usually reversible

• Can have competitive agonists and antagonists

Covalent Modulation

• Alter the rate of protein binding/activity

• Phosphorylation and Dephosphorylation

• Addition of Lipid of Carbohydrate

Covalent Modulation

• Alter the rate of protein binding/activity

• Phosphorylation and Dephosphorylation

• Addition of Lipid of Carbohydrate

Physical Factors

• Alter the rate of protein binding/activity

• Temperature

• pH

• The body regulates the amount of proteins in cells