BIOS 307: Biochemical Metabolism

• Textbook: Lehninger Principles of Biochemistry; http://bcs.whfreeman.com/lehninger/

• Course Website: http://www.uwp.edu/~barber/BIOS307/2007/BIOS307.htm

• Another useful website: http://www.genome.ad.jp/kegg/

• Office hours 1-2 PM every weekday except Wednesday, or by appointment

Grades

• Attendance/Participation 10%

• Three hourly exams 40% (First one 10%)

• Weekly assigned homework 15%

• Term paper 10%

• Final 25%

A good reason for this course:

• Typically, a required pre-med class, but…– Metabolomics, Physiomics

The age of –omics

-ome signifies the collectivity of the units in the stem

Genome – collection of genesTranscriptome – collection of RNA transcriptsProteome – collection of proteinsMetabolome – collection of metabolitesEtc.

The central dogma of molecular biology

DNA RNA PROTEIN

Gene Expression

Metabolism

Metabolites can be diagnostic

• Whether physician or patient you will find an understanding of metabolism helpful http://www.entelos.com/

• So yes, there will be memorization of pathways and metabolites, which will accompany your understanding of design and rationale of metabolic pathways and cycles. [if you want to get a start: be able to recognize various enzyme cofactors with nucleotide character (NAD, FAD, CoA, etc.), nucleotides (ATP, GTP, etc.), and amino acids]

An example: Cancer and Metabolism

PET scan reveals tumor

by highlighting areas of

increased glucose uptake

Energy Generation and Cancer Treatment

Personalizing Cancer Care

Aging (mean life span) is also influenced by genetic traits

Specific mutations have been identified in model organismssuch as worms, flies, and yeast that lead to extension of lifespan

Analysis of such mutants holds out the possibility of understandingthe molecular mechanisms of aging

-Yeast mutants lacking SIR2 have a shorter lifespan-The same is true for C. elegans (worms) lacking the SIR2 homolog-The human homolog enhances survival of cells in culture

Sir2 related proteins are found in all eukaryotes, including man: The family of proteins are known as Sirtuins

The mechanism by which Sir2 promoteslongevity is unknownbut general idea is this:

Aging

Because it consumes NAD, SIR2 has been proposed to be the monitor that connects metabolism to aging

High Calorie DietNAD is converted to NADH & unavailable for SIR2

Caloric Restriction:Less NAD used in catabolismMore available for SIR2 action

Cancer, life span - metabolism

• The intent is not to engage you with fear and consumption

• Metabolism refers to the underlying chemistry of life…thus it has a profound impact on you

Both universal and unique metabolic pathways

Generate energy from light or chemistry

Evolutionary model(s) for eukaryotic cells

Eating together leads to cellular

evolution

Review of chemical properties

Organic chemistry: Carbon

• Chemistry = Function (ie. peptide bond)

• Biomolecules commonly exist as stereoisomers (same chemical composition, distinct organization in space)– Enantiomers (mirror images)– Diastereoisomers (Non-mirror images)

Evident in sugars, amino acids, etc.

Enantiomer or Diastereomer?

Aspartame metabolism

Bio-inorganic chemistry or why do I need Zn daily?

• Coordination of metal ions provides structure for biomolecules– ATP is found only as Mg-ATP intracellularly

• Charge carriers– Nerve impulses resulting from K and Na ion channels

• Catalysis– Act as a Lewis acid/base

• Electron transfer• Activation of small molecules (i. e. N2)

Functional groups determine chemical properties

SN1 and SN2