Welcome to Biochemistry 432/832

Instructors: Vadim Gladyshev

Lori Allison

Teaching Assistant: Yun Jeong Kim

yjkim@unlserve.unl.eduClass 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