analyses of biological macromolecules
Biological macromolecules are polar
The main point of the first segment of this material is this: THE MONOMER UNITS OF BIOLOGICAL MACROMOLECULES HAVE HEADS AND TAILS. WHEN THEY POLYMERIZE IN A HEAD-TO-TAIL FASHION, THE RESULTING POLYMERS ALSO HAVE HEADS AND TAILS.
These macromolecules are polar [polar: having different ends] because they are formed by head to tail condensation of polar monomers. Let's look at the three major classes of macromolecules to see how this works, and let's begin with carbohydrates.
Monosaccharides polymerize to yield polysaccharides.
Glucose is a typical monosaccharide. It has two important types of functional group: a carbonyl group (an aldehyde in glucose, some other sugars have a ketone group instead.) hydroxyl groups on the other carbons. This is what you need to know about glucose, not its detailed structure.
Glucose exists mostly in ring structures. ( 5-OH adds across the carbonyl oxygen double bond.) This is a so-called internal hemiacetal. The ring can close in either of two ways, giving rise to anomeric forms, -OH down (the alpha-form) and -OH up (the beta-form)
The anomeric carbon (the carbon to which this -OH is attached) differs significantly from the other carbons. (note: it's easy to pick out because it is the only carbon with TWO oxygens -- ring and hydroxyl -- attached.)
Free anomeric carbons have the chemical reactivity of carbonyl carbons because they spend part of their time in the open chain form. They can reduce alkaline solutions of cupric salts. Sugars with free anomeric carbons are therefore called reducing sugars. The rest of the carbohydrate consists of ordinary carbons and ordinary -OH groups. The point is, a monosaccharide can therefore be thought of as having polarity, with one end consisting of the anomeric carbon, and the other end consisting of the rest of the molecule.
Monosaccharides can polymerize by elimination of the elements of water between the anomeric hydroxyl and a hydroxyl of another sugar. This is called a glycosidic bond.
If two anomeric hydroxyl groups react (head to head condensation) the product has no reducing end (no free anomeric carbon). This is the case with sucrose
If the anomeric hydroxyl reacts with a non-anomeric hydroxyl of another sugar, the product has ends with different properties. A reducing end (with a free anomeric carbon). A nonreducing end. This is the case with maltose.
Since most monosaccharides have more than one hydroxyl, branches are possible, and are common. Branches result in a more compact molecule. If the branch ends are the reactive sites, more branches provide more reactive sites per molecule.
Let's now turn to nucleotides and nucleic acids.
Nucleotides polymerize to yield nucleic acids.
Nucleotides consist of three parts.
Phosphate.
Monosaccharide.
Ribose (in ribonucleotides)
Deoxyribose, which lacks a 2' -OH (in deoxyribonucleotides)
The presence or absence of the 2' -OH has structural significance that will be discussed later.
There are four dominant bases; here are three of them: adenine (purine) cytosine (pyrimidine) guanine (purine)
The fourth base is (a pyrimidine) uracil (in ribonucleotides) or thymine (in deoxyribonucleotides)
Be aware that uracil and thymine are very similar; they differ only by a methyl group. You need to know which are purines and which are pyrimidines, and whether it is the purines or the pyrimidines that have one ring. The reasons for knowing these points relate to the way purines and pyrimidines interact in nucleic acids, which we'll cover shortly.
Nucleotides polymerize by eliminating the elements of water to form esters between the 5'-phosphate and the 3' -OH of another nucleotide.
A 3'->5' phosphodiester bond is thereby formed. The product has ends with different properties. An end with a free 5' group (likely with phosphate attached); this is called the 5' end. An end with a free 3' group; this is called the 3' end.
Let's look at the conventions for writing sequences of nucleotides in nucleic acids. Bases are abbreviated by their initials: A, C, G and U or T. U is normally found only in RNA, and T is normally found only in DNA. So the presence of U vs. T distinguishes between RNA and DNA in a written sequence.
Sequences are written with the 5' end to the left and the 3' end to the right unless specifically designated otherwise.
Phosphate groups are usually not shown unless the writer wants to draw attention to them. The following representations are all equivalent. uracil adenine cytosine guanine | | | | P-ribose-P-ribose-P-ribose-P-ribose-OH 5' 3' 5' 3' 5' 3' 5' 3' pUpApCpG UACG 3' GCAU 5'
(Note that in the last line the sequence is written in reverse order , but the ends are appropriately designated.)
Branches are possible in RNA but not in DNA. RNA has a 2' -OH, at which branching could occur, while DNA does not. Branching is very unusual; it is known to occur only during RNA modification [the "lariat"], but not in any finished RNA species. Amino acids polymerize to form polypeptides or proteins. Amino acids contain a carboxylic acid (-COOH) group and an amino (-NH2) group. The amino groups are usually attached to the carbons which are alpha to the carboxyl carbons, so they are called alpha-amino acids.
The naturally occurring amino acids are optically active, as they have four different groups attached to one carbon, (Glycine is an exception, having two hydrogens) and have the L-configuration.
The R-groups of the amino acids provide a basis for classifying amino acids. There are many ways of classifying amino acids, but one very useful way is on the basis of how well or poorly the R-group interacts with water
The first class is the hydrophobic R-groups which can be aliphatic (such as the methyl group of alanine) or aromatic (such as the phenyl group of phenylalanine). The second class is the hydrophilic R-groups which can contain neutral polar (such as the -OH of serine) or ionizable (such as the -COOH of aspartate) functional groups.
I was born in Japan on August 3, 1959. My natural mother died one month after I was born, apparently due to giving birth at an advanced age. Because my father was also physically frail, I was brought up by my uncle and aunt. When I use the words "father" and "mother" now, I am referring to the father and mother who raised me. Perhaps it was because of my easygoing character that I remained ignorant of my early circumstances until I was 18 years old, when my parents informed me of these circumstances. More likely, however, my blissful ignorance was due to the completely fair-minded upbringing I received by my parents, older sister and brothers, relatives and neighbours.
My parents operated a business selling and repairing carpentry tools in Toyama Prefecture. I grew up with images of my father sharpening saw-blade teeth and planes, images in which he was seemingly always busy working quietly with his hands. My mother was not only busy performing housework, but also making end-of-month collections and keeping the books of the family business until late at night. I have no memory of my parents encouraging me with words like 'study' or 'succeed.' There is no doubt, however, that the values they instilled in me were much more important than those suggested by these words. From my father, I learned the importance of working sincerely at things to which I had committed myself, and to persevere untiringly even in the face of little progress. My mother also stressed the importance of working quietly towards achieving my missions in life, without neglecting attention to details. My father passed away three years ago (1999).
Apart from my parents, I was also influenced by my grandmother. She often admonished me, using the expression "What a waste!" ("Mottai-nai!" in Japanese). While these words are approaching extinction these days, they used to be an integral part of the cultural values in Japan. My grandmother valued even the smallest of things. Once, when she noticed me crumpling up a sheet of paper to throw it away, she angrily reproached me, saying "What a waste. You could straighten that paper out and use it to blow your nose." It is no wonder the concept "What a waste!" is so ingrained in my psyche.
The prefecture name "Toyama" means "rich in mountains." Toyama is surrounded by the Tateyama Mountains to the east, other mountains to the south and west, and the Sea of Japan to the north. Just the sight of the Tateyama Mountains brings me a sense of calm. This area is blessed with bountiful nature, eliciting in me a feeling of awe towards all living things and a compelling interest in the mysteries of nature, so difficult to find in urban settings.
Expo '70 held in Osaka, Japan
I was enrolled in the Hachininmachi Elementary School in Toyama City in 1966. I cannot say that I was a particularly diligent student, especially during the lower grades. One event, however, did make a lasting impression on me, and that was Expo '70, Japan's first world fair, held in Osaka in 1970. The Exposition site displayed the future of technology, which would actually be realized 20 to 30 years later. I truly felt the power of science and technology. Our teacher for the last three years of elementary school was Mr. Kyosei Sawagaki. He taught us not by having us memorize textbooks, but through the joy of performing scientific experimentation and discovering phenomena with our own eyes. One day our teacher showed us an experiment in which boric acid was first dissolved in water, and then re-crystallized. As I watched and experienced this incredible phenomenon, I blurted out, "It's starting to snow!" While this would have been considered incorrect as an answer in a test, my teacher cherished that response. That was when I discovered that learning could be enjoyable, and not just a painful experience.
I enrolled in Toyama Municipal Shibazono Middle School in 1972. This was not an especially elite middle school, but I did apply myself singlemindedly to my studies. My efforts enabled me to attain a ranking in the top ten percent of the class.
In 1975, I enrolled in Toyama Chubu High School in Toyama Prefecture. This high school is known for its competitive first or second ranking in Toyama Prefecture as a school for sending graduates on to "first-class" universities. Together with just about every other student in the school, I devoted a great deal of effort to studying for the university entrance examination. The tenacious character I've possessed since I was a small child propelled me to successfully meet this challenge, and I was able to safely gain acceptance to the university of my choice.
View of Tateyama Mountains (as high as 3,000 meters) from Toyama City
Upon receiving my notification of acceptance to the university, my parents noticed that they were obliged to submit to the university, among other things, a copy of my official family register. After much mental anguish, they decided to inform me of the secret of my birth. The truth came as a considerable shock to me, and the trauma surged over me in waves for a long time afterwards. At the same time, however, it was a chance for me to assert my independence. The thought grew strong in me that since I had gone to the trouble of being born, I might as well be useful in helping people live long and healthy lives. And this thought has always resided in the back of my mind.
In 1978, I entered Tohoku University, into the Department of Electrical Engineering, Faculty of Technology. I suppose the reason I chose electrical engineering was because I had always been interested in electricity, involving myself in such projects as building radios from the time I was a child. Moreover, I thought that electrical-related skills would be useful upon graduation, and that it would be easy to find a job among the electronics-related businesses so active in Japan at that time. Perhaps as a reaction to the tremendous efforts I had made to pass the university entrance examination, I let up somewhat in my first- and second-year studies at the university. As a result, my grades suffered in German class, and I was forced to repeat the year. Aware that I had placed a burden on my parents, from that point on, I diligently applied myself to my studies. In my senior year at the university, we were obliged to complete a graduation research project, and mine was entitled "Absorption of a Plane Wave by an Impedance-Loaded Dipole Array Buried in a Lossy Medium." The objective of the research was to reduce the ghost effect of television broadcast waves by placing an array of line-shaped conductors in front of a building to prevent the reflection of electric waves from the building. I was guided in my research by Professor Saburo Adachi. Needless to say, my present research endeavors have practically no relevance to that subject.
The Faculty of Technology of Tohoku University is renowned for its tradition of practical studies. For instance, historical individuals associated with the university include Professor Kotaro Honda for his contributions in metallurgical engineering, Professor Hidetsugu Yagi, the inventor of the wellknown Yagi antenna (patented in 1940), and Professor Jun-ichi Nishizawa for his opto-electronics and semiconductor research. In such an environment, I was able to study things that could be of immediate usefulness to the world. That learning experience undoubtedly served me well when I eventually entered the work force.
When it came time to find employment, I set my sights on becoming an engineer at a home electronics manufacturer, a field that was closely related to my major at university. I took an entrance examination for employment at one such company, but failed the examination. Despite my desire to be an electrical engineer, I am sure my answers to the electricity-related questions were somewhat less than acceptable. Even though I failed, however, I still hold that company in high regard.
At that point, I decided that there was no need to focus solely on electrical engineering, especially because I had only two years of electrical-related knowledge. I turned to my mentor, Professor Adachi, and he was kind enough to introduce me to Shimadzu Corporation. I learned from Shimadzu's employment literature that the company was manufacturing Xray devices and other types of medical equipment. This struck a chord with me, rekindling the possibility that I might yet satisfy my desire to help suffering people, albeit indirectly. I decided to take the employment examination, and that time, I passed without problem. However, instead of being assigned to the area of medical equipment, I learned I was to be involved in research and development of analytical instrumentation. Fortunately, that field also held interest for me, and it became the central area of my work.
Kyoto city is home to Shimadzu's main factories and research divisions, and has fostered six out of Japan's nine Nobel Prize laureates in scientific fields, including Prof. Hideki Yukawa (selected in 1949), Professor Shin-ichiro Tomonaga (1965), Prof. Ken-ichi Fukui (1981), Prof. Susumu Tonegawa (1987), Prof. Ryoji Noyori (2001), and myself. Probably no one can explain exactly why so many laureates hail from Kyoto, but the knowledge of this fact did have somewhat of an effect on me. I might even have mused that I could reach to such a level if I were to put my heart and soul into the effort.
I joined Shimadzu Corporation in 1983, and was immediately assigned to the Central Research Laboratory, a new department which had been established in 1980. At that time, there were three laboratories, for mechanical-, chemical- and electrical-related research, respectively. I was assigned to the laboratory for electrical systems-related research, and joined a team charged with developing component technology for analytical instruments. This team comprised Dr. Tamio Yoshida, Mr. Yoshikazu Yoshida, Mr. Satoshi Akita, Mr. Yutaka Ido, the one member who joined the company with me, and myself. We were a very young team, with an average age in the 20's, with me being the youngest of all.