Biology: Biological Molecules and Enzymes

Lipids:

The major groups of lipids include: 

1. Fatty acids (FA's) - Component of phospholipids, glycolipids, and sphingolipids of cell membranes. Composed of long chains of carbons (usually even # of carbons) with a carboxylic acid at the end, and separated into saturated and unsaturated FA's. Used for long-term energy storage. 
2. Triacylglycerols (Triglycerides) - Are also known as "fats" and "oils", which are constructed from a three carbon (hence tri) backbone called glycerol, which is attached to three FA chains. Their function is to store energy.
3. Phospholipids - Lipids with a phosphate group attached. More specifically, phosphoglycerides are exactly like triglycerides except that one of the FA's is replaced with a phosphate group. The phosphate group is polar, and the FA isn't, so this makes this molecule amphipathic. This is an integral molecule in cell membranes.
4. Glycolipids - Just like phosphoglycerides, except that one or more carbohydrates are attached to glycerol instead of the phosphate group. (Remember: Glyco = Carbohydrate) Also amphipathic. Largely found in the human nervous system. 
5. Steroids - Four-ringed structures. (Includes some hormones, vitamin D, and cholesterol)
6. Terpenes - Often part of pigments in the body. Include vitamin A, which is important for vision. 
7. Waxes - Formed by an ester linkage between a long-chain alcohol and a long-chain FA. 

Another class of lipids are the 20-C eicosanoids which include prostaglandins. They are released from the cell membrane as local hormones (paracrine). Aspirin (anti-inflammatory) is commonly used as an inhibitor for the synthesis of prostaglandins. 

Sphingolipids are similar to phosphoglycerides in that they have a long chain FA and a polar head group. However, instead of glycerol, the backbone is called a sphingosine.

Some important facts:

• Lipids that make up the cell membrane: phopholipids, glycolipids, steroids, and sphingolipids.
• The long carbon chains of lipids, specifically the triglycerides and FA's, are useful for allowing energy storage. 
• Oxidation of FA's liberates large amounts of chemical energy for a cell. 
• Lipids are also useful as precursors for signaling molecules because they can pass through cellular membranes.
• Adipocytes contain almost nothing but triglycerides.

Lipid Transport:

Lipids are transported through the blood via lipoproteins, which contain a lipid core surrounded by phospholipids (amphipathic) and apoproteins (the proteins that bind lipids to make lipoproteins).

     -Lipoproteins are classified by their density. The greater the ratio of lipid to protein, the lower the density. 

          -Classes include chylomicrons, VLDL, LDL, and HDL, 

Carbohydrates:

Allow for the storage of large amounts of energy, but not as high as lipids. They can form in long chains via dehydration reactions, essentially making larger molecules with the production of water. 

Monosaccharides --> polysaccharides 

Ex: Glucose --> Glycogen  (polymer with alpha linkages) 

Polysaccharide for plants: Starch

     -Plants also use glucose molecules to form cellulose (structural material rather than energy storage through beta linkages. Humans can digest glycogen and starch, but not the beta linkages of cellulose.)

Most cells absorb glucose via facilitated diffusion. Insulin increases the rate of facilitated diffusion for glucose and other monosaccharides. 

Alpha vs Beta glucose: (Direction of OH, Alpha = down, Beta = up) "Bottom's up" 

Starch = alpha 1,4, linkages 

Glycogen = alpha 1,6, linkages + 1,4, linkages

Cellulose = beta 1,4, linkages 

Nucleotides:

Building blocks of every organism. Three components: 

1. A five carbon (pentose) sugar 
2. A nitrogenous base 
3. A phosphate group 

A nucleoside consists of a pentose sugar attached to a nitrogenous base. Nucleotides are formed by the very addition of one or more phosphaate groups to a nucleoside. 

Monomer to polymer:

Nucleotides --> Nucleic acids

Nucleotides are joined together by phosphidiester bonds between the phosphate group of one nucleotide and the third carbon of the pentose sugar of the other nucleotide. This is the "sugar-phosphate backbone"

-Examples of nucleotides: ATP, cAMP, NADH, FADH2

-NADH is an example of a dinucleotide.

-Written in the 5` to 3` direction (5th carbon to 3rd carbon direction)

Bases: A,C,T,G 

Purines: Adenine, Guanine

Pyrimidines: Cytosine, Thymine     

Purine-Pyrimidine pair H bonds: 

AT = 2 H bonds (2AT, "Twat")

CG = 3H bonds

RNA is different from DNA in that: 

1. Carbon number 2 on the pentose sugar is not "deoxygenated" (it has a hydroxyl group attached)
2. RNA is always single stranded
3. Contains pyrimidine uracil instead of thymine
4. It can move through nuclear pores and is not confined to the nucleus. 

Amino Acids and Proteins: 

Monomer to polymer: 

Amino acids (AA's) --> polypeptides

Hydrolysis of a peptide bond involves the breaking at the amide junction. 

In humans, 9/20 of the amino acids are essential, meaning they cannot be manufactured by the body and thus must be ingested directly. Digested proteins reach the cells of the body as single AA's.

R groups of amino acids can be divided into 4 categories:

1. Acidic
2. Basic
3. Polar
4. Non-Polar

*All acidic and basic R groups are also polar. 

Four structures of proteins: 

1. Primary - Sequence of straight chain AA's. 
2. Secondary - Conforms into two kinds of secondary structures:
1. α-helix
2. β-pleated sheets
3. Tertiary - 3D shape formed by curls and folds. Five forces contributing to the tertiary structure:
1. Covalent disulfide bonds between two cysteine AA's on different parts of the chain, creating the dimer cysteine 
2. Electrostatic (ionic) interactions, mostly between acidic and basic side chains
3. H bonds
4. van der Waals forces
5. Hydrophobic side chains pushed away from water toward the center of the protein (hydrophobic bonding)
4. Quaternary - Two or more polypeptide chains joining together. Same five forces at work. 

Two types of proteins: globular and structural. Globular proteins function as enzymes, hormones, membrane pumps and channels, receptors, intracellular transport and storage, osmotic regulators etc.

Minerals are dissolved inorganic ions inside and outside of the cell. They act as cofactors assisting enzyme or protein function. For example, iron is a mineral for heme, the prosthetic group of cytochromes. They also assist in the transport of substances by creating electrochemical gradients across membranes. 

Enzymes:

-Typically globular proteins, although there are a few nucleic acids that act as enzymes. Acts as a catalyst, lowering activation energy. 

Reactants = Substrates

-Enzymes are typically bigger than substrates. 

As the relative concentration of substrate increases, the rate of the reaction also increases. 

     -Vmax = maximum rate of reaction

     -Turnover number = max number of substrate molecules one active site can convert to product in a given unit of time. 

     -Michaelis constant (Km) = substrate concentration at which the reaction rate is equal to 1/2Vmax.

          -Indicates how highly concentrated the substrate must be to speed up the reaction. If a higher concentration is needed, the enzyme must have a lower affinity for the substrate. Thus Km is inversely proportional to enzyme-substrate affinity. 

To function efficiently, enzymes need cofactors, which can be coenzymes (organic molecules, like water soluble vitamins, and divided into cosubstrates and prosthetic groups) or metal ions (minerals). 

     -An enzyme without its cofactor is called a apoenzyme and is completely non-functional.

     -An enzyme with its cofactor is called a holoenzyme and is functional. 

Regulation of Enzyme activity, four primary means: 

1. Proteolytic cleavage (irreversible covalent modification) - Enzymes are released into their environment in an inactive form called a zymogen or proenzyme. When it is cleaved in a specific way, it is activated. Changes in environment or cleavage of other enzymes may trigger this. (This is to taking something you bought from the internet out of its package and throwing the package away, leaving you with the product to use.) 
2. Reversible covalent modification - Some enzymes are (de)activated by phosphorylation or the addition of another modifier like AMP. The removal of such modifier is almost always accompanied by hydrolysis. Phosphorylation occurs in the presence of a protein kinase. (This is carefully cutting out the package and saving the package in-case you want to re-package.) 
3. Control proteins - These are protein subunits that associate with certain enzymes to activate or inhibit activity. Calmodulin or G-proteins are two examples. (This is allowing a house robot to open the package for you whenever it finds necessary, and it's not much in your control.)
4. Allosteric interactions - Modification of an enzyme's configuration through the binding of an activator or inhibitor at a specific binding site on the enzyme. (This is having a product without a package, but instead with an empty battery cartridge, in which you put the batteries or take out the batteries at your own discretion.) 

Inhibition:

Products that exert negative feedback to not resemble the substrates of the enzymes they inhibit, so they do not bind to the active site. This is called allosteric inhibition.

Upstream enzymes involved in a particular synthetic metabolic pathway typically have allosteric inhibitory sites that bind the final amino acid product. In that final product is present in the environment, it acts as an allosteric inhibitor in a negative feedback loop, preventing synthesis of additional product.

• Positive Cooperation - When substrate binds to the enzyme, and the substrate's conformational change allows for the next substrate to bind much easier to the enzyme. (Negative cooperation is the opposite.) 

Inhibitors: 

1. Irreversible inhibitors - Bind to enzymes via covalent bonds. 
2. Competitive inhibitors - Binds reversible with noncovalent bonds to the active site. The only type of reversible inhibitor to bind to the active site and no other site of the enzyme (Raise Km but do now change Vmax)
3. Uncompetitive inhibitors - Bind at a site other than the active site. 
4. Mixed inhibitors - Bind at a site on the enzyme other than the active site and thus do not prevent the substrate from binding. 
5. Noncompetitive inhibitors - Bind just as readily to enzymes with a substrate as to those without. Act on more than one type of enzyme since they do not resemble the substrate. Since they cannot be overcome by excess substrate, they lower Vmax, but do not change Km. (NOncompetitive inhibitors have NO preference between the enzyme and enzyme-substrate complex. Therefore Km does not change theoretically. However, as enzyme-substrate fit decreases, Km increases, and vice versa.) 

Enzyme Classification: 

1. Oxidoreductases - Catalyze the transfer of electrons or hydrogen ions, like oxidation-reduction reactions. 
2. Transferases - Catalyze reactions in which groups are transferred from one location to another.
3. Hydrolases - Regulate hydrolysis reactions.
4. Lyases - Catalyze reactions in which functional groups added to double bonds or, conversely, double bonds are formed via the removal of functional groups. (Breaks things apart) 
5. Isomerases - Catalyze the transfer of groups within a molecule, with the effect of producing isomers. 
6. Ligases - Catalyzes condensation reactions coupled with the hydrolysis of high energy molecules. (Forms molecules from smaller parts) 

*All enzymes contain nitrogen. 

-Ligases sometimes called synthetases. 

-Lyases sometimes called synthases.

-Kinases phosphorylates molecules
-Phosphorylases dephosphorylates molecules 

Difference b/w Enzyme Inhibitors