Lecture 1: Biomolecules

Question 1

What are the 4 major classes of chemicals in biochemistry

Answer 1

1. Lipids (smallest), Carbs, Proteins, Nucleic acids (biggest)
2. All are polymers (Except lipids: oligosaccharides because too small)
3. All are macromolecules (except lipids: they are smaller than 5000Da)
4. All are hydrolyzable

Question 2

Water as a solvent

Answer 2

1. Water is a good solvent as it is small, abundant, and sticky (polar)
2. As a solvent, it allows solvation (hydration) reactions to occur which causes a solvation (hydration) shell

Question 3

Hydrolysis vs dehydration

Answer 3

1. Hydrolysis: exergonic (energy released)
2. Dehydration: endergonic (energy put in)

Question 4

Lipid structure & function

Answer 4

1. Structure: Any biological molecule with low solubility (doesn’t dissolve in water) because they have a large portion of hydrocarbons (high diversity: only need to have hydrocarbon)
2. Function:
3. Membrane structure: Major components of cell wall: phospholipids, glycolipids, cholesterol
4. Energy storage: due to them being anahydrous (have no water) we can store them without them being too heavy
5. Hormone signalling: ex: steroids, prostaglandins

Question 5

The two types of lipid derivatives are:

Answer 5

1. Fatty acid derivatives: carboxylic acid+ long hydrocarbon chain
2. terpene derivatives: 2 5C isoprenes together

Question 6

Fatty acids

Answer 6

1. Unbranched, hydrocarbon chain ending in carboxylic acid
2. Chains vary in length (most are 12-24 even number C)
   2a. Short (<5C): infinitely soluble in water
   2b. Medium (6-12)
   2c. Long (14-20):
   2d. Very long (22, 24): very very low solubility
3. Fatty acids are synthesized via 2C acetyl CoA

Question 7

Fatty acid saturation

Answer 7

1. Saturated: only single carbon-carbon bonds (ex: palmitic acid (16:0))/not flexible
2. Unsaturated: has double bonds
   2a. Nomenclature: triangle^(double bond position)
   2b. Synthesis of double bonds beyond carbon 9 isn’t possible in humans (get those from diet)
   2c. Cis double bonds create a kink=increases fluidity=lowers melting point of double bond
   2d. Types: Monounsaturated (only 1 double bond) & Polyunsaturated: more than 1 double bond

Question 8

Fatty acid transport in blood

Answer 8

1. Most common way of transport: fatty acid derivatives in lipoproteins
2. Albumin: binds noncovalently to up to 7 fatty acids
3. Free fatty acids: very few

Question 9

Fatty acid derivatives: eicosanoids

Answer 9

1. DAG/phospholipids->archinodic acid->eicosanoids (20C): ex->prostaglandin
2. prostaglandins (20C):
   2a. Prostaglandins structure: polyunsaturated fatty acid derivatives that have a cyclopentane ring
   2b. Prostaglandins function: do vasodilation (lowers blood pressure), increase pain/inflammation, controls smooth muscle contraction (peristalsis), induces labour
   2c. Prostaglandins are blocked by aspirin

Question 10

Fatty acid derivatives: Saponifiable lipids

Answer 10

1. Soponification: ester (RCOOR) + water = fatty acid (RCOOH) + alcohol (HOR)
   1a. In lab: Soponification occurs in basic conditions…overall exergonic (protonation step at end)
   1b. In cell: Soponification occurs in neutral conditions so it needs a catalyst (lipase)
2. Fatty acid derivatives (soponifiable lipids): fatty acids are attached to a glycerol (3OH+FA), sphingosine(attaches at amine+FA) and alcohols (OH+FA=wax)

Question 11

Fatty acid derivatives: Waxes structure & definition

Answer 11

1. Long chain fatty acids esterified to a long chain alcohol: very low solubility (many hydrocarbons)
2. Waxes are structural lipids that are hydrophobic (water resistant) and malleable at room temp
3. Function: used on outside of organism for cleaning and lubrication

Question 12

Fatty acid derivatives: Glycerolipids

Answer 12

1. Structure: fatty acids forming ester linkages with 3C glycerol (carb+3OH) backbone
2. Types: triacylglycerol (glycerol+3FA), Glycero-phospholipids, glyceroglycolipids

Question 13

Fatty acid derivatives: Glycerolipids: TAG & DAG

Answer 13

1. TAG: 3FA+ glycerol (3C+3OH): dehydration reaction that forms 3 acyl (-COR: alcohol) groups that attach to glycerol (triacylglycerol/TAG)
   1a. Functions of TAG: Store energy (oxidation of fatty acid releases large energy) and provide thermal insulation
2. Diacylglycerol (DAG): only 2 acyl groups attach to 2 C’s from the glycerol (one of the C’s in the glycerol remains empty)

Question 14

Ester linkage

Answer 14

1. A bond between oxygen and carbon dioxide
2. -oate

Question 15

Fatty acid derivatives: Glycerolipids: Glycerophospholipids

Answer 15

1. Phosphatidic acid (no head group): Has a phosphate attached to the third carbon of a glycerol backbone of a diacylglycerol (2 acyl groups)
2. Glycerophospholipids (have a head group attached to the phosphate):
   2a. choline: positive (named phosphatidylcholine): amine+2methyls->Most abundant phospholipid
   2b. ethanolamine: positive (named phosphatidylethanolamine): amine
   2c. serine (named phosphatidylserine)
   2d. inositol (OH on hexane ring; phosphatidylinositol): intracellular signalling

Question 16

Fatty acid derivatives: Glycerolipids: Glycero-glycolipids

Answer 16

1. Carb (water and carbon) is attached directly to the third carbon of a diacylglycerol
2. NOT found in humans

Question 17

Fatty acid derivatives: Sphingolipids

Answer 17

1. Lipids with sphingosine backbone (18C; Has amine (NH2) on carbon 2 and a trans double bond between C4-5)
2. Every sphingolipid is derived from a ceramide (sphingosine+ fatty acid attached to amine)

Question 18

Fatty acid derivatives: Sphingolipids: sphingo-phospholipid

Answer 18

1. Sphingosine backbone of a ceramide + first C is attached to a phosphate and the phosphate is attached to a head group
2. Only sphingophospholipid in humans is sphingomyelin with a choline backbone (ethanol+quaternary amine (+))

Question 19

Fatty acid derivatives: Sphingolipids: sphingo-glycolipids

Answer 19

1. When first carbon on sphingosine backbone of a ceramide is attached to a head group (carbohydrate)
2. All glycolipids without a phosphate group, important in Brain/neural tissue
3. Types:
   3a. Cerebrosides (simple carbohydrate): one carbohydrate
   3b. Globosides (simple carbohydrate): more than one carbohydrate
   3c. Gangliosides (charged on headgroup(+)): more than one carbohydrate + sialic acid

Question 20

Terpene derivatives

Answer 20

1. Terpene: polymers of isoprene (horse shape if cis) that are nonsaponifiable
   1a. Terpenes formula is (C5H8)n where n=2+
2. Terpene ->cholesterol (a steroid) -> sterols (vitamins A, D, E, K, B-carotene, Qionone/coenzyme Q, squalene, bile acids)
   2a. Cholesterol: 4 rings where 3 are 6C and 1 is 5C: head group=alcohol: 6+2 carbon tail: methyl in 2 groves
   2b. Cholesterol ester (wax/saponifiable/less soluble): fatty acid attaches to head group alcohol on cholesterol
3. Steroids: their skeleton is the 3 6C and 1 5C rings we see in cholesterol

Question 21

Terpene derivatives: cholesterol

Answer 21

1. Cholesterol is a terpene derivative with 6 isoprene units
2. Function:
   2a. maintains stability of cellular membranes: decreases fluidity at high temperatures and increases it at low temperatures
   2b. Precursor to steroid hormones: testosterone and estrogen

Question 22

Membrane (structural) lipids

Answer 22

1. Structural lipids include Phospholipids (80%), glycolipids (5%) and cholesterol (15%), waxes
2. These lipids are Amphipathic molecules: polar at one end and nonpolar at others:
   2a. Form micelles: By being amphiphatic, they aggregate in water where their polar heads go towards the solution and non polar tails are away=forms spherical Micelle spontaneously
   2b. Liposomes: vesicle surrounded by aqueous solution: surrounded by 2 layers of phospholipids (phospholipid bilayer)
3. Structural lipids combine to form the fluid mosaic model:
   3a. Electrostatic forces (van der Waals) and ionic forces hold heads together
   3b. Hydrophobic effect holds both leaflets together to form the lipid bilayer

Question 23

Lipoproteins

Answer 23

1. Big micelles that are Water soluble lipid transporters that are made in liver and intestines
   1a. Monolayer composed of phosphatidylcholine, sphingomyelin, cholesterol and apolipoproteins
   1b. Core is filled with TAGs and cholesterol esters
2. Types
   2a. Chylomicrons (least dense/largest): made in smooth ER of enterocytes…deliver TAG to adipose, muscle tissue and liver
   2b. VLDL: made in liver and transport endogenous lipids and cholesterol from liver to tissues (as they lose TAGs they become IDL (VLDL remnants) which are taken up by liver and metabolized to LDL)
   2c. LDL: have apoB100 to deliver cholesterol to tissues
   2d. HDLs (most dense/smallest): made in peripheral tissues and they transport excess cholesterol to liver (act as negative feedback signal to reduce cholesterol synthesis)

Question 24

Apolipoprotein function

Answer 24

1. Structure: bind lipids together, stabilize lipoproteins
2. Communication: interacting with lipoprotein receptors on cell surfaces, initiating uptake and clearance of lipoproteins
3. Metabolism: serve as cofactors for enzymes that metabolize lipoproteins

Question 25

Amino acids

Answer 25

1. Amino acids/residues are linked by peptide bonds (N-C) to form a polypeptide=long polypeptide is called a protein 2. 20 alpha amino acids with carboxyl group (2), amino group (9), hydroxyl group and R group (all chiral except glycine) 2a. Polar: STCNQ 2b. Nonpolar: LIMP VAG 2c. Charged: DEKRH 2d. Aromatic: WYF

Question 26

Relative configuration: D or L

Answer 26

1. D or L: all 19 common amino acids are L amino acids (since glycine isn’t chiral, it doesn’t have a configuration) 1a. Levorotatory (-): plane of polarized light rotates counterclockwise and dextrorotatory (+): plane polarized light rotates clockwise 2. Steps: 2a. Number all carbons: carbonyl carbon should be lowest number possible 2b. If carbonyl carbon is on bottom, rotate structure 180 degrees so its at top (or at end just change lettering: D->L or L->D) 2c. Find chiral carbons: look at one with highest numbering 2d. If OH is on Right of chiral carbon=D…if OH is on left of chiral carbon=L

Question 27

Isoelectric point (PI)

Answer 27

1. Amino acids are amphoteric (can donate acid or base) and amphiprotic 2. Have specific pKa for each regions: amino (+)=9, carboxylic acid (-)=2 2a. PH>Pka: deprotonated 2b. PH

Question 28

Primary structure of protons

Answer 28

1. The number/sequence of its amino acid residues: disulphide bonds covalently connect residues 2. Native conformation of a protein is determined by its amino acid sequence 2a. Proteins can vary making them polymorphic but even they have crucial/conserved regions called consensus sequence (most common amino acid sequence)

Question 29

Secondary structure of proteins

Answer 29

1. Backbone: Refers to identifiable, localized spatial arrangements of atoms of the backbone 2. Amino acids are connected by a peptide bond (N-C): trans configuration exists 99.6% of the time except when in proline 3. Types: held via H bonding 3a. Alpha helix: right handed spiral with negative c term and positive N term for a dipole: held together by hydrogen bonds 3b. Beta pleated sheets: parallel and antiparallel (2 hydrogen bonds/amino acids) 3c. Beta turns: on outside of protein so polar/charged residues common (proline and glycine common here)

Question 30

Tertiary structure of proteins

Answer 30

1. 3d shape of a protein: native conformation if a protein 2. Forces that contribute to tertiary structure: 2a. hydrophobic effect: most important for structure formation/folding, water allows R groups to turn inward to protein and pack tightly 2b. van der Waals: hold core together) 2c. hydrogen bonds/ion pairing (salt bridge: increases entropy of the solvation layer 2d. disulfide bonds: covalent so strongest bond; formed via oxidation reaction between cysteines in ER

Question 31

Quaternary structure of proteins

Answer 31

1. 2+ polypeptide chains that associate to form one protein

Question 32

Denaturation

Answer 32

1. Denaturation is when a protein loses its 2, 3, or 4 structure due to heat, salt or pH 1a. Urea: H bonds 1b. Salt/pH change: ion pairing 1c. Mercaptoethanol: disulfide bonds 1d. Organic solvents: hydrophobic forces 1e. Heat: all forces

Question 33

Classification of proteins

Answer 33

1. Globular (corpuscular): soluble in water, function as enzymes, hormones, membrane pumps/channels, membrane receptors, inter/intracellular transport/storage, osmotic regulators, immune response etc. 2. Fibrous (fibrillation)/structural: made from long polymers, maintain/add strength to cellular/matrix structures, insoluble in water

Question 34

Carbohydrates

Answer 34

1. Sugars or saccharides Cx(H20)x: carbon + water (so polar and water soluble) 2. Nomenclature: 2a. Anomeric carbon: (ring) attached to 2 oxygens or (linear) carbon double bonded to oxygen…this carbon has lowest numbering possible 2b. D vs L: (ring) if C6 above=D, below =L or (linear) if OH is on right of biggest number chiral carbon (D) if on left (L) 2c. Alpha vs beta: (ring) alpha is opposite of C6 and beta is same side as C6

Question 35

Monosaccharides

Answer 35

1. Glucose: 6C, OH down 2. Galactose: 6C, OH up 3. Fructose: 5C

Question 36

Disaccharides

Answer 36

1. When monosaccharides form glycosidic bonds: Can be alpha (OH down) or beta (OH up) linkages (different anomers) 2. Types 2a. Sucrose: glucose + fructose (a 1, 4) 2b. Lactose: galactose + glucose (b 1,4) 2c. Maltose: glucose + glucose (a 1,4)

Question 37

Glycogen

Answer 37

1. Glycogen: branched glucose polymer found in muscle and liver cells 1a. Better energy storage than fat because its short term efficient, energy readily available because it produces ATP faster through glycolysis, can provide energy without oxygen 1b. HOWEVER, fat is better for long term energy storage because its anhydrous so its lighter 2. Forms a1,4 and a1,6 bonds

Question 38

Plant polysaccharides

Answer 38

1. Starch: stores energy 1a. Has alpha linkages and comes in 2 forms: amylopectin (branched link glycogen: a 1, 4 linkages and a 1, 6 linkages) and amylose (not branched so only a 1, 4 linkages) 2. Cellulose: builds cell wall 2a. Not branched so b 1, 4 linkages: since beta animals can’t digest cellulose

Question 39

Nucleotides

Answer 39

1. Building blocks of nucleic acids (DNA and RNA) and play a role as energy carriers and cell signaling 2. Nucleotide Structure: 5C sugar called ribose, nitrogenous base and 1, 2, or 3 phosphate groups (nucleosides don’t have phosphate group) 2a. Phosphate groups are linked together by phosphodiester bonds (these bonds can be hydrolyzed in exergonic reactions) 2b. Nitrogenous base: organic base with nitrogen and there are 2 types->pyramidines (Single ring-cytosine, thymine, uracil) and purines (double ringed-adenine and guanine)

Question 40

DNA vs RNA

Answer 40

1. RNA has hydroxy group at 2’ C 2. RNA is always single stranded in human 3. RNA uses uracil not thymine 4. RNA may leave nucleus but DNA doesn’t 5. RNA is transcribed from DNA template; DNA is replicated from DNA template

Question 41

DNA structure

Answer 41

1. Primary: sequence of nucleotides 1a. Each nucleotide is bound to the next via a phosphodiester bond between the 5C and 3C carbons which creates 5’->3’ directionality: results in sugar phosphate backbone 2. Secondary: any recognizable structure achieved by a string of nucleotides (1 double helix=1 chromosome) 3. Tertiary: folding patterns of large chromosomes

Question 42

Watson crick model of DNA

Answer 42

1. 2 strands lie antiparallel which forms dsDNA: sequence is written 5’->3’ 2. 2 strands are held together by hydrogen bonds between purines and pyramidines 2a. Base pairing: Adenine makes 2H bonds with thymine, guanine makes 3H bonds with cytosine (higher melting temperature) 3. Complementary strands (when bases match up) curl into double helix with polar phosphate sugar backbone towards aqueous solution

Question 43

DNA tertiary structure

Answer 43

1. Chromosome: single molecule of DNA in a double helix and it is bound to proteins and small amounts of RNA (DNA-protein-RNA material: chromatin) 2. Chromatin 2a. Heterochromatin: tightly condensed, not transcribed … 2 types of heterochromatin->faculative (can become euchromatin) and constitutive (remains condensed always: centromere and telomeres) 2b. Euchromatin: relaxed state, transcribed 3. Histones: protein in chromatin that has many positive amino acids (arginine, lysine) which attracts negative phosphates on DNA backbone which causes helix to wrap tight around histones 3a. Histones group together in octamers called nucleosome

Question 44

CDNA cloning process:

Answer 44

1. Uses DNA polymerase, DNA ligase and reverse transcriptase