Quiz 1

Biochemistry

describes molecular structures, mechanisms and chemical processes that make life work → biochemistry works at the level of atoms

Coexistence: we are not isolated organisms as humans → we need other organisms to live
Ex: Photosynthetic cells produce O2 and CHO from CO2 and H2O
Heterotrophic cells (like humans) produce CO2 and H2O from the O2 and CHO photosynthetic cells make

The Key: all parts are interconnected via interactions and under control → proteins play a central role in this
Ex: protein—protein, protein—metabolite, protein—membrane, protein—DNA & RNA
It is also a dynamic network:
Product of one rxn = substrate of next
Interconnections maintain system balance

The 4 main categories of biomolecules

Amino acids and proteins: spontaneously fold, bind to other molecules, catalyze reactions

Nucleotides and polynucleotides: store info, transmit/translate info, catalyze rxns (RNA)

Saccharides and polysaccharides: Structure, E, recognition

Lipids: Bilayer, E (storage, like triglycerides)

All contribute to biosynthesis

Origin of biochemistry

The big bang… distribution of matter and energy in the universe
Patterns are very important
Main considerations: type of force, density, Temperature, momentum, time, history

Beginning of chemistry

Big bang makes quarks → protons and deuterons → small molecules: ³He, ⁴He, ⁷Li, no chemical complexity yet

Then large clouds of H gas collapsed under force of gravity to form stars → now we get nuclear fusion at the very hot core of stars!! This allows us to make larger atoms, but not molecules because chemical bonds cannot withstand the temperatures of the star core
Star core temp >10⁶K
Chemical bonds cannot withstand temp >10⁴K

Nuclear reactions in star cores

“Burning”
H-burning:
4¹H → ⁴He + 2e⁺

He-burning:
3⁴He → ¹²C

C-burning:
¹²C + ⁴He → ¹⁶O
¹²C + ¹²C → ²⁴Mg

O-burning:
¹⁶O +⁴He → ²⁰Ne
¹⁶O + ¹²C → ²⁸Si

Si-burning
²⁸Si + ²⁸Si → ⁵⁶Fe

So basically we are made of stardust because of star burning
Stellar burning cannot make elements heavier than ⁵⁶Fe 🤓
Supernovae produced all heavier elements → star deaths that release lots of E

Chemistry as we know it

Covalent bond formation: b/w 100 - 5000K
Happens mainly on/in planets and some moons (bc of the T)
So many chemical compounds → there are patterns of chemical bonds

Matter = solid, liquid, or gas depending on T and P

Properties of living systems

In the cell, all the chemical reactions happen in balance. We know this because a cell will look basically the same now and a long time from now because molecules are broken down and replaced

There are only limited types of compounds and reactions
So many interconnections
Cells are self replicating

Molecules of life evolved to have special properties
Self organizing behaviors:
→ protein, DNA, RNA, CHO fold
→ lipids form bilayers and monolayers
→ Proteins, DNA, RNA, Lipids, small molecules → can all combine to form complexse
Some molecules are smart and can perform many tasks, like ribosomes

All of metabolism

All of the chemical reactions in the cell → so many interconnections, more interconnections that the number of reactions, and these are only partially known

The interconnections form the complex pattern of life → we do not yet understand this… while we can track the reactions for an individual molecule (its synthesis and breakdown) we do not yet understand how the separate reaction sets for each kind of molecule are connected to each other

Why did living systems evolve to have these particular few thousand reactions?

Reactions of living systems do not occur on the biological time scale in the absence of a catalyst → not all reactions are turned on at the same time → control

Each reaction requires a catalyst. They occur too slowly for life on their own → all these reactions evolved as a set that is under control
99% catalyzed by proteins (enzymes), 1% catalyzed by RNA (ribozymes)
Enzymes catalyze reactions by lowering the energy barrier

Catalysts communicate with each other to interconnect all the reactions

Cell balance

Only certain molecules enter cells… and the molecules that leave the cell are generally different from those that enter (but number of atoms is still the same) → some molecules that leave the cell will be more oxidized

Oxidation is favorable because we have so much O2 from photosynthetic organisms → ex: glucose → E released by its oxidation → spontaneous reaction

Synthesis/breakdown in the cell are in balance and require E → where does this E come from??
Actually 🤓favorable reactions (like oxidation or photosynthesis) will drive all synthesis/breakdown reactions that a cell needs

You will never accumulate too much of one thing because of this balance

Amino acids

Amino NH2 Group, Carboxyl COO- group, H, R (side chain)

Peptide bond = bond b/w Amino group of one AA and carboxyl group of second AA

Amino acid stereochemistry

Only L isomers are found in natural proteins
Remember we go to CORN - L (going clockwise)

Stereoisomers have different shapes → important for binding
will rotate plane of polarized light in opposite ways and react differently in biosynthesis

Amino acid charges

Charges will be on ionizable groups depending on pKa and pH
Ex: charges in ion pairs (salt bridges) will control hemoglobin function (binding to O2). Ion pairs will only form if each group is charged

The amino group is + chg and the carboxyl group is - chg at pH 7, but this varies with side chain
The amino and carboxyl groups on the alpha carbon are only ionizable if they are terminal

How do we know if the proton is on or off?

HENDERSON HASSELBACH
pH = pKa + log([A-]/[AH])

To determine if an ion pair forms, you must apply the HH eqtn separately to each group to get the probability it is protonated or deprotonated and then multiply the probabilities of interest.
Ex: You care if His is protonated because that is when it will be + and you care if Asp is deprotonated because that is when it will be - → you multiply the probability of His being protonated by the probability of Asp being deprotonated → this will be the probability of an ion pair forming given at a given pH

General Rules:
pH « pKa → protonated
pH » pKa → deprotonated
pH = pKa → unprotonated = protonated

Amino acid side chains

20 coded by DNA, but by testing proteins you can find more than that because those were chemically modified

Hydrogen Bonds

formed because of the partial + and - charge on the atoms involved in a bond between an electronegative atom and a less electronegative atom

The hydrogen bond is the strongest if the 2 electronegative atoms and the Hydrogen are in a straight line (180 degrees). Typically the angle is 130-180

Hydrogen bond donors will have a partial positive:
any Hs attached to an electronegative atom (O, N, S), even if the EN atom has a formal + charge
Ex: NH, NH2, alcohols, thiols, NH3+, NH+, NH2+
Hydrogen bond acceptors will have a partial negative
EN atoms (O, N, S) Ex: carbonyls, thiols, alcohols, water, -N=

Peptide bonds and protein solubility

peptide bonds are a covalent bond formed via a condensation reaction (AKA H2O is released)
They occur between the amino group (NH3+) of one amino acid and the carboxyl group (COO-) of another amino acid
Free amino acids are soluble in H2O because of the charges on the amino and carboxyl groups, but a peptide is less soluble in H2O than free AA depending on the R because you lose 1 + and - charge for each peptide bond formed

We always write amino acid sequence from left to right (amino terminus to carboxyl terminus)
To know the direction of the chain, remember “N - Calpha - C double bond O”

Hydrophobic interaction

aliphatic = oily, non aromatic carbon chains
Hydrophobic interaction is the tendency to force nonpolar groups out of water due to Gibbs free energy!!! delta G = deltaH - T deltaS

If we were to place an peptide made only out of aliphatic amino acids, the freedom of H2O to form H bonds with itself would be restricted → less entropy (disorder) → protein folds so that aliphatic nonpolar side chains exposed to H2O are minimized → H2O has more freedom to form bonds with itself

Sidechain behavior in peptides is determined by

Hydrophobicity scale! Nonpolar = hydrophobic, polar = hydrophilic → polarity of side chains drives folding
“Actual” polarity can depend on whether it is in an alpha helix, beta sheet, in H2O vs membrane, and the pH (because pH affects charge)
○ = oxygen
● = carbon
□ = nitrogen
Isoleucine and threonine have chiral carbons in them

General information about proteins

“linear” polypeptide: no peptide bond b/w sidechain carboxy and sidechain amino groups (ex: b/w glu and lys)

Initial synthesis occurs on a ribosome, directed by mRNA → proteins can be modified after initial synthesis via chemical modification of the AA or cutting out a piece of the protein (like to activate it)

Size: they can be super big or small and one protein can consist of one or more polypeptide chains

MW vs molecular mass
MW has no units. It is the ratio to 1/12 of ¹²C
Molecular mass has units of Daltons
1Da = 1g/mol… so in the end does this distinction really matter? probably not

Myoglobin and hemoglobin

Myoglobin: monomer inside cells that binds to 1 O2 and stores it

Hemoglobin: tetramer in RBC that can bind up to 4 O2 and delivers it to tissues

O2 is not supa soluble in blood