Welcome to Biochemistry 432/832

Instructors: Vadim Gladyshev Lori Allison

Teaching Assistant: Yun Jeong Kimyjkim@unlserve.unl.edu

Class web page:

http://www-class.unl.edu/bioc432/bioc432.htmTuesday/Thursday 11.00-12.15 pm

Beadle Center Auditorium

OutlineInformation

SyllabusStudent profile

Introduction to the courseIntroduction to metabolismOverview of glycolysis

Useful web sitesUseful web sitesTHE LITERATURE OF BIOCHEMISTRY

http://www-class.unl.edu/bioc839/literature.html THE FIELD OF BIOCHEMISTRY

Major Journals Major Reviews

YOUR OWN FIELD OF RESEARCH REVIEWS KEY WORD SEARCH WHERE TO SEARCH?

How to Read a Research Article Composition of a full paper Composition of a communication What to read?

Skepticism

Useful web sitesNational Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov

Access to the primary literature (Pubmed) http://www.ncbi.nlm.nih.gov/PubMed/

On-line journals J. of Biol. Chemistry http://www.jbc.org/Proc. of the Nat. Acad of Sci. USA http://www.pnas.org/

Sequences (Entrez)http://www.ncbi.nlm.nih.gov/Entrez/

Structures (Structure)

http://www.ncbi.nlm.nih.gov/Structure/Clusters of orthologous groups (COS) http://www.ncbi.nlm.nih.gov/COG/

Information

You are welcome to come without an appointment, but it is better to E-mail or call before you come

You are responsible for all material covered in the chapter that is discussed in the class. You will have the reading assignment for each class period except exams.

Some sections of certain chapters may be excluded from the reading assignments and exams, and if it happens, I will tell you beforehand.

No excuses for missing exams. Medical school interview is not an excuse.

InformationRecent scientific papers that describe discoveries or breakthroughs in areas being covered during the course, will be discussed and corresponding concept questions may be included in the exams and bonus questions.

Methods to study: read the chapter (reading assignment) before the respective class period. First, you could read quickly the chapter to get an idea what is it about. The second time you read, pay a particular attention to concepts, but knowledge of details may also be necessary. After the class, read the chapter again and also read the lecture notes. It should be enough for a good performance on exams.

Overview of Metabolism

Metabolism - OverviewMetabolism is a sum of chemical changes that convert nutrients into energy and finally to complex finished products of cells (The process through which organisms acquire and utilize energy for their function)

Do we know all metabolic pathways?

Metabolism - Overview

Metabolism consists of catabolism and anabolism

Catabolism: degradative pathwaysUsually energy-yielding!

Anabolism: biosynthetic pathwaysenergy-requiring!

Metabolism - Overview

Degradation: biomolecules –building blocks – common intermediates - final products

Metabolism - OverviewPrinciples: Metabolic pathways are irreversible (because they must be regulated)Metabolic pathways have (first) committed stepMetabolic pathways are regulated Metabolic pathways are compartmentalized

Principles: anabolic and catabolic pathways must differ in at least one step in order to be regulated

Anabolic & catabolic pathways involving the same product are not the sameSome steps may be commonOthers must be different- to ensurethat each pathway is spontaneousThis also allows regulation mechanisms to turn one pathway and the other off

Principles: Metabolic pathways are compartmentalizedMitochondria (TCA cycle, OxPhos, fatty acid oxidation, amino acid breakdown)Cytosol (glycolysis, fatty acid biosynthesis, pentose phosphate cycle)Nucleus (DNA replication, transcription, RNA processing)ER (Rough ER: synthesis of membrane and secretory proteins, smooth ER: lipid and steroid biosynthesis)Golgi (posttranslational processing of proteins)

Pathways consist of sequential steps- The enzymes may be separate- Or may form a multienzyme complex- Or may be a membrane-bound system- New research indicates that multienzyme complexes are morecommon than once thought

Metabolism - OverviewUnderstanding of pathways: Sequence of reactionsMechanisms of each reactionRegulation of pathways

Hypotheses or exploration ???Methods:Inhibitors (accumulation of intermediates)Genetic defects (also accumulation of intermediates)Genetic manipulations: animals (transgenic, knockout), expression in certain tissuesEmerging methods: sequence methods (genome projects), bioinformatics, high throughput gene expression methods(microarray analyses - hybridizations on membranes, slides, chips)

Systems Analysis of MetabolismCatabolic and anabolic pathways, occurring

simultaneously, must act as a regulated, orderly, responsive whole

• catabolism, anabolism and macromolecular synthesis • Just a few intermediates connect major systems - sugar-

phosphates, -keto acids, CoA derivatives, and PEP • ATP & NADPH couple catabolism & anabolism • Phototrophs also have photosynthesis and CO2 fixation

systems

Intermediary metabolism

• Cells need a constant supply of energy• NADH, NADPH and ATP• ATP - energy currency• NADPH - reducing power• Glucose --> NADH --> ATP• Glucose --> NADPH --> biosynthesis (reductive)

Metabolism - energy considerations

Redox in Metabolism• NAD+ collects electrons released in

catabolism• Catabolism is oxidative - substrates

lose reducing equivalents• Anabolism is reductive - NADPH

provides the reducing power (electrons) for anabolic processes

NAD+/NADH ratio: 725 Concentration: 0.5 mM

NADP+/NADPH ratio: 0.015 Concentration: 0.2 mM