Welcome to Biochemistry 432/832 Instructors: Vadim Gladyshev Lori Allison Teaching Assistant: Yun Jeong Kim [email protected] Class web page: http://www- class.unl.edu/bioc432/bioc432.htm Tuesday/Thursday 11.00-12.15 pm Beadle Center Auditorium
Dec 21, 2015
Welcome to Biochemistry 432/832
Instructors: Vadim Gladyshev
Lori Allison
Teaching Assistant: Yun Jeong Kim
[email protected] web page:
http://www-class.unl.edu/bioc432/bioc432.htmTuesday/Thursday 11.00-12.15 pm
Beadle Center Auditorium
OutlineInformation
Syllabus
Student profile
Introduction to the course
Introduction to metabolism
Overview of glycolysis
Useful web sitesUseful web sites
THE 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.
Information
Recent 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 - Overview
Principles: Metabolic pathways are irreversible (because they
must be regulated)
Metabolic pathways have (first) committed step
Metabolic 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 same
Some steps may be common
Others must be different- to ensure
that each pathway is spontaneous
This also allows regulation
mechanisms to turn one pathway
and the other off
Principles:
Metabolic pathways are compartmentalized
Mitochondria (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 more
common than once
thought
Metabolism - OverviewUnderstanding of pathways:
Sequence of reactions
Mechanisms of each reaction
Regulation of pathwaysHypotheses or exploration ???
Methods:Inhibitors (accumulation of intermediates)
Genetic defects (also accumulation of intermediates)
Genetic manipulations: animals (transgenic, knockout), expression in certain tissues
Emerging 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