Getting Started. Speaking the Language and Walking the Landscape

1. Getting Started. Speaking the Language and Walking the Landscape To know biochemistry is to communicate in the language of the science. Communication is absolutely essential in silent thought and spoken words. Words conjure up images that stay with you. Correct answers on exams will depend on how well you interpret what is being asked. Simply put, If you don’t understand the question, you won’t know the answer. The language of biochemistry must not be a foreign language to you. Biochemical terms for the most part are taken from organic chemistry, but many are unique to the science itself. For example proteins, carbohydrates, nucleic acids, etc. have their own descriptors that convey specific meanings. It is not necessary that you memorize the exact wording of the definitions, only the meaning and unique concept, structure, reaction, etc. they are meant to convey.

2. Metabolites, Macromolecules and Molecular Complexes: Small molecules such as amino acids, monosaccharides, fatty acids, and nucleotidesare common in living systems. Such substances are referred to as “metabolites”, implying they are primed for chemical change. It is, however, the giant molecules with molecular weights in the hundreds of thousands that sets biochemistry apart from anything you experienced in organic chemistry. DNA, for example, represents two intertwined chains with a molecular weight in the millions (click 1). LDL likewise is a giant complex composed of lipid and proteins (click 1) and ATP synthase is a huge assembly of proteins that is composed of more than 20 different proteins in the mitochondria (click 1). Thus, biochemistry runs the gamut of molecules from the very tiny to giant molecular assemblies. ATP Synthase DNA LDL Particle

3. H H H H R R R’ C C C CO-NH COOH COOH C COOH R’ NH2 NH2 NH2 CH2OH CH2OH CH2OH CH2OH O O O O OH OH OH OH O HO HO OH OH HO OH OH OH OH OH Structure vs Function: Structure plays a preeminent role in the function of biomolecules. A simple amino acid, for example has 3 important structural features linked to its function: (1) a –COOH group, a –NH3 group, and a variable R group (click 1). The carboxyl and amino group are designed to joins amino acids together in peptide bonds (click 1). Amino acids therefore are designed to “polymerize”, i.e., unite with one another to form macromolecules built from smaller defined units. Similarly, carbohydrates join to one another through acetal bonds, which in biochemistry are call glycosidic bonds (click 1). The lesson here is to see how these orgainic principles of bonding carry over to biochemistry and the structure of biomolecules.

4. Little Begets Big The assembly of larger biomolecules is based on a simple repeat pattern. Proteins, polysaccharides, membrane lipids, RNA and DNA are built from simpler molecules. This organizing principle should not be overlooked. To help you see the importance of modular design, consider the various stages of molecular assembly for each category of biomolecules (click 1) Building Block First Stage Second Stage Final Stage Amino acids Polypeptides Peptides Proteins Monosaccharides Disaccharides Oligosaccharides Polysaccharides Monoacylglycerols Diacylglycerols Triacylglycerols Fatty acids Mononucleotides Dinucleotides Oligonucleotides Polynucleotides Each stage can be represented by a stable set of molecules. For example, common disaccharides include sucrose, maltose, lactose; common peptides are oxytocin, vasopressin, growth hormone; common polypeptides include insulin, glucagon.

5. O O CH2OH H2-C-O-C-R COOH H2-C-O-C-R H-C-OH H-C-OH H-C-OH H-C-OH CH2OH CH2OH CH2OH CH2OPO3H D-glycerol Monoacylglycerol Monoacylglycero- phosphate D-glycerate What’s in a Name Nomenclature is important in any science. Names given to compounds, complexes, reactions, etc. have a rationale basis and it will up to you to spot the reason behind the name. Lets start with the word “glycan”. A glycan is literally any carbohydrate. It can be a simple substance or a complex. A “proteoglycan” is thus a protein with a carbohydrate appendage. If the appendage is small and the protein is the major component, its called a glycoprotein with emphasis on the word “protein”. The amino acid “glycine” derives its name because of its sweet taste, like a carbohydrate, i.e., a glycan. All of these terms come from a simple root word. Another important root word is “glycer” as in glycerol. Glycerol is a 3-carbon trihydroxy alcohol that is a major building block of lipids (click 1). The alcohol groups serve as attachment points for fatty acids. From this simple stem compound come compounds such as the “acylglycerophophates, glycerate, monoacylglycerols, etc (click 1).

6. It would be virtually impossible to list names, prefixes, abbreviations, etc. of all the biomolecules. The impact of this lesson, however, is to alert you to how names give important clues to the structural features of molecules. Below are common chemical prefixes that wind their way into biochemical terminology (click 1). Acyl: implying a fatty acid attached Alpha: implying the first carbon from a carboxyl group As you study your lessons pay close attention to the names and see if you can determine why the molecule is so-called. This is one way to prepare for exams where the question may assume that you are familiar with the compound being asked. Aceto: implying an acetyl group Amido: implying an amide group in the molecule Beta: implying the second carbon from a carbonyl group Glyco: implying a carbohydrate appendage Methyl or meth: implying a CH3- group: Phospho: Implying a phosphate group Thio: Implying a sulfur group Mono, di, tri, oligo, poly: implying one, two, three, several, many units Tetra, penta, hexa, hepta, octa: implying 4, 5, 6 and 7 units Homo: implying sameness in two or more components Hetero: implying a difference in two or more components

7. Test and Extend Your Knowledge of Terminology Q. What structural features would you expect to see in the amino acid “methionine”? A: The name implies the presence of a sulfur atom (thio) and a methyl group Q: What structural difference exists between a “heteropolysaccharide” and a “homopolysaccharide? A: Hetero would be expected to be composed of more than one type of sugar unit; homo would have all units the same. Q: Hydrolysis is a term in biochemistry that is used to signify the breaking down of a compound by inserting a water molecule across the bonding atoms. What would be the hydrolysis products of a polysaccharide? A protein? DNA? RNA? Triacylglycerol? A: Polysaccharide = monosaccharides. Protein = amino acids. DNA = deoxyribose, phosphate, and a base. Triacylglycerol = glycerol and 3 fatty acids. Q: Assume you have a protein that is classified as a “homopolymer”. The hydrolysis of all the peptide bonds in this protein would yield how many types of amino acids. A: One Q: Can one observe the principle of modular design in a simple molecule as opposed to a complex structure like a protein? A: Yes. Cholesterol is a simple molecule in that it cannot be separated from or hydrolyzed into smaller molecules. Cholesterol, however, is built entirely from isoprene units that polymerize during the synthesis process.