Lecture 4 Biochem

Amino acids serve as building blocks of proteins

Amino acids are intimately connected with all phases of chemical and physical cell activity

Amino acids as precursors for cell signaling molecules, such as vitamins and hormones

1. enzymes 2. transporters 3. oxygen carriers

Embedded in cell membranes

There are 20 different amino acids

Name of amino acids is derived from amine (basic) and carboxyl (acidic) group properties

Amino acids are Bound to the same carbon called α‐carbon

1. carboxyl group
2. amine
3. variable group

Variable group define amino acid characteristics, properties, and interactions with other molecules.

In nature (on Earth) most of the amino acid found in living organisms are of the L‐configuration.

A spontaneous reaction would yield both enantiomers

The alpha carbon shows chirality

Only L‐amino acids are incorporated into proteins.

The only amino acid that does not show chirality is glycine

At the physiological pH (7.4), the amine group is positive (+) charged and the carboxylic group is negative (–).

Occurs when the net charge of the molecule is zero

Low pH ‐> more acidic (positive charged)

High pH ‐> more basic (negatively charged)

The smaller the pKa value, the stronger the acid

If pH drops below pKa‐> become positively charged

If pH goes above pKa ‐> become negatively charged

The polarity and charge of R groups is important because it affects the non-covalent interactions

Essential amino acids are needed in the diet because it can’t be made by the organism

REMEBER PVT TIM Hall ("private Tim Hll")
phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, leucine, and lysine

Essential amino acids classification varies in respect to age.

Hisitidine and arginine

Growing humans (children) synthesize histidine at low rate, so they need dietary histidine to maintain nitrogen balance.

Arginine is formed from arginino succinate as part of urea cycle.

Since arginine is converted to ornithine, it may not be available for protein synthesis in children.

For adults, arginine is not an essential amino acid because the urea cycle generates enough.

Aromatic‐>containing a planar unsaturated ring of atoms

Aliphatic‐> carbon atoms form open chains (alkanes)

Aromatic and Aliphatic

hydroxyl, sulfhydryl, and carboxyamides

Carboxylates and amines

The amino acid glycine is an important precursor for hemesand purines

Polar side chains are usually found on the surface of proteins

If you place two cysteine sulfhydryls next to each other, they will form a covalent disulfide bond, which helps to stabilize the structure of proteins.

Histidine is precursor of histamine, which is important for inflammatory reactions and as a
neurotransmitter.

Arginine is important for synthesis of nitric oxide (NO) important in the urea cycle

Arg and Lys are both abundantly found in histones, that associate with DNA to make chromosomes.

Acidic amino acids form salt bridges and polar interactions.

Glutamate is major excitatory neurotransmitter

Acidic amino acids are important in other metabolic roles and for attachment of carbohydrate chains in glycoproteins.

Primary

Secondary structure

Tertiary structure

Quaternary structure

Amino acids chains start from the amino-terminal end to the carboxyl-terminal end.

The R groups are arranged in a trans‐configuration in relation to each other in order to fall into the lowest energy of configuration

Double bonds and peptide bonds cannot rotate whereas the alpha carbons single bonds can rotate!

The local structure of the protein backbone is stabilized by intramolecular and sometimes intermolecular hydrogen bonding of amide groups.

The alpha helix (α‐helix) has a right‐handed spiral conformation, four residues turn

A Beta strand (β‐strand) is a stretch of polypeptide chain, typically 3 to 10 amino acids long stabilized by hydrogen bonds

Beta sheets can be parallel or antiparallel.

1. non-colavent interactions
2. disulfide
3. metal ion coordination

1. hydrogen bonding
2. ionic interactions
3. van der Waals forces
4. hydrophobic packing

Metal ion coordination is sometimes needed for protein activity (breaking bonds)

When proteins fold into quaternary structure, the proteins can bind to other proteins and DNA/RNA

1. ribosome
2. hemoglobin
3. actin microfilament

Domains are a section of protein with a specific activity

A catalytic site is a specific site and amino acids that perfrom a specific acitivity

1. the amino acids that make up the protein
2. secondary and tertiary structures
3. environment (pH, temperature, and solvent)

Enzymes, transport proteins, and globular proteins are water soluble proteins.

Fibrous, actin, and collagen are water insoluble proteins.

Myoglobin an oxygen storing protein related to hemoglobin. Only one polypeptide chain.

Myoglobin is found in the cytoplasm of cells, in an aqueous environment

Soluble proteins fold and have hydrophobic centers and hydrophilic outside to interact with water

Denaturing proteins involves the disruption and possible destruction of both the secondary and tertiary structures

Primary structure remains the same after a denaturation process

1. hydrogen bonds
2. salt bridges
3. disulfide bonds

Thermal energy may disrupt the hydrogen bonds that hold the protein together

Urea is a very polar molecule, breaks disulfide bonds, alters the H-bonds of water.

Detergents are surfactant compounds that have cleansing properties and denature by solubilizing hydrophobic groups.

Chaotropic agents are chemical substances in an aqueous solution that can destroy the hydrogen bond network between water molecules and denature by weakening hydrophobic effect.

Triton X 100 and Tween 20 are examples of detergents.

Ethanol is an example of a chaotropic agent.

Ammonium sulfate tend to stabilize protein structures and increase the melting temperature.

Calcium chloride destabilize proteins and lower the melting temperature

Salt interrupts hydrogen bonds

Salt can also be used to purify proteins

Changing the pH will alter the charge of the protein, (like Zwitterions) which in turn will alter protein solubility and overall shape

Solubility of proteins increases lightly in presence of salt, but high amounts of salt lead to their percipitation

Poteins use a cooperative folding model to go from their unfolded state to their native or folded state.

Thermodynamics play a role in achieving the folded state and lowest free energy conformation

Protein folding begins co‐translationally.

Molecular chaperons hsp60 and hsp70 work with other proteins to help fold newly synthesized proteins

Autosomal recessive disorder

Sickle cell anemia is caused by a point mutation in the 6th amino acid of beta globin
from glutamic acid to valine

Sickle cell anemia causes hemoglobin protein misfolding and forms strands that cause red blood cells to appear like a sickle

Sickle cell anemia has been shown to protect against malaria infection.

Prion disease is caused by misfolded prion proteins

In prion diseases, the PrPSc conformation initiates other PrPc prion molecules to convert to the toxic form

β‐strand interactions lead to a polymerization into amyloid fibers which then form plaques

1. Alzheimer’s
2. Parkinson’s

Prions are infectious proteins that are highly resistant to destruction

1. Scrapie in sheep
2. Mad cow disease in cattle

1. Kuru (spongiform in cerebellum)
2. Creutzfelt‐Jakob Disease (CJD)
3. alpha-synuclein's prion‐like behaviors in mammals (Parkinson theory)

Only about 15 percent are