METABOLIC PATHWAYS IN LIVING SYSTEMS
 BIOL 6233 / BIOL 3233
FALL 2011

Instructor: Dr. Carroll D. Rawn; Office: Rm 410 McNulty Hall. This 3-credit lecture course meets Monday 5:45-7:00 PM and Wednesday 6:30-7:45 PM in McNulty Hall room 106.  Office hours (tentative): 9:00-10:00 am Mon., Wed. and 4:00-5:00 pm Tue., Thu.; others by appointment; any changes needed will be announced in class or posted on-line, on my web page at http://pirate.shu.edu/~rawncarr/.   Office phone: (973)-761-9054.  E-mail: rawncarr@shu.edu

Prerequisites for undergraduates:

▪ General Biology I & II, Genetics, Organic Chemistry I & II, Cell Biology
▪ Senior status and 3.0 science GPA.
▪ It is recommended that the student have some elective biology coursework beyond Genetics and Cell Biology. Vertebrate Physiology and Molecular Biology would be helpful.

It is assumed that graduate students, having completed the B.S., will have biology elective credits beyond Cell Biology and Genetics.

Textbook:  Biochemistry, 4^th edition, by R. Garrett and C. Grisham, 2010.  Published by. Thomson, Brooks/Cole/Cengage Learning. There are several good biochemistry books available, each with its own strengths and limitations. None provides adequate treatment of metabolism for this course because, in part, (1) the trend in texts for some years has been to try to cover molecular genetics in addition to metabolism, energetics, enzymology, and "refresher" background chemistry and (2) texts routinely exclude some of the metabolism found in plants and microbes, especially secondary metabolism. As a result, (1) some of the material in this book, as well as the others, does not belong in this course (e.g. chapters 12, 16, most of part IV) and (2) handouts and assigned readings from other sources must be used to supplement the text's coverage of metabolism.

A textbook is useful as a reference, if only as a repository of the many details of the major metabolic pathways. Even where it's not necessary to memorize details, we still need to see them in order to understand the pathways. However, exams will not be based upon the content of this particular text. Therefore, you may use a different text for reference, as long as it is recent and is comprehensive in its topic coverage. It should cover most of the material listed under "Topics" below.

Electronics in class. You may record the class sessions on a small tape recorder; in fact, you are encouraged to do so, since it is important to concentrate on what's being said and written on the board rather than trying to write it all. However, use of laptops, cell phones, and other electronic gadgets is not allowed in class.  Cell phones must be turned off or muted during class meetings.

Grading

The course grade will be the average of three exams, one after each lecture block (see Topics below). Exam dates will be announced in class at least one week in advance. The third exam will be done in the week of final exams.  The nature of the subject matter means that the second and third lecture blocks will depend to some degree on material covered in the first part of the course. Exams will reflect the cumulative nature of the material, but each exam will stress its own block of material.

The grade scale for each exam and the course grade (undergraduates) is: 93-100 A; 90-92 A-; 87-89 B+; 83-86 B; 80-82 B-; 76-79 C+; 68-75 C; 65-67 C-; 60-64 D+, 55-59 D, 0-54 F. The scale is the same for graduate students except that there are no C-, D+, or D grades possible; that's a college policy. Therefore, grades below C (65 points) correspond to letter grade F.

No exam grades will be dropped. No other work will be used as exam substitutes or grade supplements. Everyone is expected to take the exams on schedule. As a final item in determining the course grade, I will consider quality of class participation. This factor will not replace or make up for a poor exam grade, but it might weigh significantly in borderline cases after the exam average has been calculated. Though exams will not be returned for you to keep, you will have the opportunity to review them.

Although senior undergraduates and graduate students are together in lecture, graduate students will be held to a higher standard and will have exams that are more challenging; that may include some dependence on non-text assigned readings.

Academic integrity: The penalty for cheating on any examination is a zero grade on that exam and a report of the event to the department chairperson and the college dean.

Philosophy

The course's topic coverage is summarized below. Although some factual material must be committed to memory, the primary concern is an understanding of how metabolic pathways operate in living systems: their integrated nature, modes by which they are regulated, their functions, their organization in space and time. Most lecture topics are dealt with in the text but in different ways in most cases and not in the same detail as in lecture. Some lecture topics are not in the text at all. You are encouraged to ask and answer questions in class. Everyone is expected to come to class ready to "think out loud", which will require keeping up with the material from one class meeting to the next.

Although the course deals with topics that are usually identified as "biochemistry", it does not cover topics such as enzyme kinetics, macromolecule structure, bioenergetics, and catalysis models in as much detail as biochemistry courses usually do. The importance of such topics is not ignored, but emphasis here is on the operation of metabolic pathways as they exist in organisms: their components, locations, functions, integration, and regulation. So, the depth and breadth of treatment of pathways is greater here than in biochemistry courses. Ideally students interested in metabolism would take this course and one in biochemistry too eventually. The two types of courses complement one another, not just in content but in the different perspectives of the chemist and the biologist in this field of common interest. This course is presented with a biologist's perspective.  The course touches many issues of practical importance and interest such as nutrition, exercise, obesity, diabetes, inherited disorders, and mechanisms of action of medications and poisons/toxins.

The discussion focuses on the cellular and molecular levels of organization, where the fundamental similarities of life forms are most easily recognized. Metabolism in complex organisms will be considered also at tissue, organ, and organ system levels; the obvious differences among tissues and organs reflect specializations in metabolism. The relatedness of disciplines such as vertebrate physiology, endocrinology, immunology, molecular biology, and cell biology are readily seen, since the discussion of metabolism draws upon these. Also, for the people who have not yet found any application for the organic chemistry that they learned, here it is.

In dealing with metabolism at these several levels the course often uses the human body as an example of a complex metabolic system, but metabolism in other species is included.  Journal readings will be assigned for various topics, as needed, since no single text fits our needs ideally, as noted above.

In the first part of the course it will be necessary to memorize the details of glycolysis, the Krebs cycle, and mitochondrial electron transport. So many pathways flow into these or arise from them that they are centrally important in the energy economy of all cells. It is necessary, therefore, to learn this core of metabolism thoroughly. Beyond this first block of material, though, less memorization of new facts is required. In fact, after the first exam the other two exams will be the "open book" type. So, organization and understanding of the material are to be the emphasis.

Topics

The course has three parts, with roughly equal time given to each, a bit more in Part I due to its foundation character.  The following is a summary of most of the topics to be covered. If it becomes necessary to change the placement or inclusion of any of these, the changes will be announced in class.

Part I topics include:  The concept of pathway and its relation to genome, transcriptome, proteome, and metabolome (the cult of "-ome").  General features of metabolic regulation such as: enzyme specificity, isozymes, induction/repression, enzyme turnover, compartmentation, enzyme inhibition models, allostery, cooperativity, channeling, enzyme structure modification.  Coenzymes, cofactors, prosthetic groups.  Reversibility of reactions.  Basic kinetics.

Glycolysis, Embden-Meyerhof pathway, fermentation, Krebs cycle, electron shuttles between cytosol and mitochondrion, electron transport, oxidative phosphorylation, substrate level phosphorylation. Anaplerotic reactions, "dark" CO₂ fixation, P/O ratio, respiratory quotient, respiratory control, uncoupling, Pasteur effect, aerobic fermentation.

Part II topics include:  Pentose phosphate pathway, pentitols. Fatty acid oxidation. Gluconeogenesis, lactate oxidation, Cori cycle, glyoxylate cycle. Polysaccharide turnover, e.g. glycogen, starch, cellulose, pectins, chitin, other hexosans and pentosans. Protein-carbohydrate complexes. Glucuronate-gulonate pathway, ascorbate metabolism, fructose and lactose metabolism. Fatty acid synthesis, fat synthesis, phospholipid and glycolipid turnover, sterol/steroid synthesis and other isoprenoids. Ketone bodies.

Part III topics include:  Amino acid turnover, urea cycle, one-carbon transfers, glucogenic and ketogenic amino acids, shikimic acid pathway. Protein turnover.  Porphyrin turnover.  Metabolism of purines, pyrimidines, nucleic acids.  Photosynthesis: photosystems, photophosphorylation, carbon fixation cycles.  Nitrogen fixation, nitrogen oxides.  Polyamines, alkaloids, phenolics.  Synthesis of selected coenzymes, plant hormones, antibiotics, toxins (not covered elsewhere).  Secondary metabolism (various perspectives of what and why).

About office hours and question/answer activity: Every class session begins with a call for questions, and questions are encouraged during class. And, of course, the scheduled office hours time is available for discussing course material outside of class time. Although email communication can be effective for several purposes, it is not an effective vehicle for trying to discuss course material. In order to avoid wasted time and miscommunication, our dialogue in Q and A about course material needs to be face to face.

Disability Services Statement:
Students at Seton Hall University who have a physical, medical, learning or psychiatric disability, either temporary or permanent, may be eligible for reasonable accommodations at the University as per the Americans with Disabilities Act (ADA) and/or Section 504 of the Rehabilitation Act. In order receive such accommodations, students must identify themselves at the Office of Disability Support Services (DSS), provide appropriate documentation and collaborate with the development of an accommodation plan. The DSS phone number (973) 313-6003. For further information, please go to http://www.shu.edu/offices/disability-support-services/index.cfm