cmb chapter 2

8/18/2019 Cmb Chapter 2

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Linking Sugars Together: – Glycosidic bonds are –C —O —C – links between sugars. – Disaccharides are used as a source of readily available

energy. – Oligosaccharides are found bound to cells surface

proteins and lipids, and may be used for cell recognition Polysaccharides are polymers of sugars joined by glycosidic

bonds. – Glycogen is an animal product made of branched glucose

polymers. – Starch is a plant product made of both branched and

unbranched glucose polymers.

structural polysaccharides – Cellulose: plant product made of unbranched polymers – Chitin: component of invertebrate exoskeleton made – GAGs: composed of two different sugars and found in

extracellular space.

2. LIPIDS are a diverse group of nonpolar molecules.• Fats are made of glycerol linked by three ester bonds to three

fatty acids. – FAs are unbranched hydrocarbons with one carboxyl

group; they are amphipathic. – Saturated FAs lack C=C double bonds and are solid at

room temperature. – Unsaturated FAs have one or more C=C double bonds and

are liquid at room temperature.

Steroids are four-ringed animal lipids that have beenimplicated in atherosclerosis. Phospholipids are amphipathic lipids that are a major

component of cell membranes.

3. PROTEINS are polymers of amino acids and form a diverse groupof macromolecules. They exhibit a high degree of specificity.

They have a variety of cellular functions.

The Building Blocks of Proteins

– have an α carbon, an amine group, a carboxyl group, and

a variable R group .

– in nature occurs as the L stereoisomer.

– are linked together by peptide bonds into a

polypeptide chain to make a protein.

Peptide bonds form between the α-carbonyl and the α-aminoof participating amino acids.

Amino acids differ in the R group attached to one of the

bonds of the α-carbon.

– R groups may be polar charged; polar uncharged;

nonpolar.

THE STRUCTURE OF PROTEINS• Primary structure , the sequence of amino acids in the

polymer, is critical to the protein function.• Secondary structure refers to the conformation of

adjacent amino acids into α-helix, β-sheet, hinges, turns,turns, loops, or finger-like extensions.

• Tertiary structure is the conformation of the entirepolymer.

–

It is stabilized by noncovalent bonds. – It is studied by X-ray crystallography. – Proteins can be fibrous or globular. – Myoglobin: The First Globular Proteins Whose Tertiary

Structure Was Determinedo Stores oxygen in muscle cells.

o Has a heme prosthetic group that binds O2.o Structure derived using X-ray crystallography.

• Quaternary structure refers to proteins composed ofsubunits.

– It refers to the manner in which subunits interact.

A. Polar charged - contain R groups that act as stronger organicacids, bases; can form ionic bonds

B. Polar uncharged - R groups weakly acidic or basic; not fullycharged at pH 7; can form H bonds with other molecules like watersince they have atoms with a partial negative or positive charge

C. Nonpolar - R groups hydrophobic; generally lack O & N; cannotinteract with water or form electrostatic bonds; vary primarily in size &shape; allows them to pack tightly into protein core

D. The other three – glycine, proline, cysteine 1. Glycine (R = H) - small R group makes backbone flexible & able to moveso it is useful in protein hinges; small R group allows 2 backbones (of same or

different protein) to approach closely 2. Proline – R group forms ring with amino group (imino acid); hydrophobicamino acid that does not readily fit into orderly secondary structure (a-helix) 3. Cysteine – R group has reactive —SH; forms disulfide ( —S —S —) bridgewith other cysteines often at some distance away in polypeptide backbone

• R groups may have other properties. – The α-carbon of proline is part of a ring, creating kinks – nature of the R groups determines the function of the protein – Post-translational modifications

• Phosphorylation of Tyr, Thr, Ser• Acetylation of Lys

•

Domains occur when proteins are composed of two or moredistinct regions. Each domain is a functional region • Conformational changes are non-random movements

triggered by the binding of a specific molecule. • Different proteins can become physically associated to form a

multiprotein complex.• Protein Folding is a process that occurs in various steps.

• Anfinsen observed that unfolding is due to denaturation, broughtabout by various agents.

• Removal of denaturing agents could lead to refolding.

Two alternate pathways for protein folding:

• Proteins may assume their native conformation through a series of steps.

• Proteins may fold along pathways without intermediate forms.

• Smaller proteins with single domains fold faster than larger proteins withmultiple domains.


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PROTEIN MISFOLDING• Creutzfeld-Jakob Disease (CJD) results from misfolded

protein in the brain. – Healthy brains contain a normal protein, PrP c.

– CJD brains have PrPSc, which is identical or similar to PrPc but ismisfolded.

– “Mad cow disease”, kuru, and scrapie are also caused by PrPSc.

• Alzheimer’s disease (AD) involves misfolded proteins thataccumulate in the brains of affected individuals. – A membrane-bound protein in brain neurons, called amyloid

precursor protein (APP) , is cleaved by two secretase enzymes.

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In individuals genetically predisposed to AD one of the cleavageproducts is A β42, a protein that misfolds and self-associates into

amyloid plaques.

– All drugs for treatment of AD are aimed at management ofsymptoms.

– Pursuit of new drugs for AD aimed at:

– Prevent formation of A β42 peptide.

– Remove the A β42 peptide once it has formed. – Prevent interaction between A β molecules.

Molecular chaperones are “helper proteins” to prevent nonselectiveinteractions during protein folding to achieve proper 3D conformation.• Hsp 70 family bind emerging proteins and prevent inappropriate

interactions.

• Chaperonins allow large new proteins to assemble without interferencefrom other macromolecules. TriC processes up to 15% of the cells’

proteins.

proteome is the entire inventory of an organism’s proteins.

Proteomics uses advanced technologies to perform large-scalestudies on diverse proteins.• Proteins are separated using gel electrophoresis.

• Proteins are identified using mass spectrometry and high speed computers.

Protein microarrays (protein chips) allow researchers to screenproteins for various activities and disorders.Site-directed mutagenesis allows researchers to make alterationsin single amino acids by altering the DNA encoding a protein.

Protein Adaptation and Evolution• Proteins are subject to natural selection.• Members of a protein family are thought to have evolved from a

single ancestor gene.• A particular protein may have different versions (isoforms) that

are tissue- or stage-specific.

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NUCLEIC ACIDS are polymers of nucleotides that store andtransmit genetic information.

• Nucleotides are connected by 3’ -5’ phosphodiester bondsbetween the phosphate of one nucleotide and the 3’ carbonof the next.

• consists of three parts:1. A five-carbon sugar2. A phosphate group3. A nitrogenous base

• Bases are either purines or pyrimidines.o The purines are adenine and guanine in both DNA

and RNA.o

The pyrimidines are cytosine and uracil in RNA;uracil is replaced by thymine in DNA.

• Deoxyribonucleic acid (DNA) holds the genetic

information in all cellular organisms and some viruses.

• Ribonucleic acid (RNA) genetic material in some viruses• RNA is usually single stranded and DNA is usually

double stranded.• RNA may fold back on itself to form complex three

dimensional structures, as in ribosomes.

• RNA may have catalytic activity; such RNA enzymes arecalled ribozymes.

• Adenosine triphosphate (ATP) is a nucleotide thatplays a key role in cellular metabolism, whereasguanosine triphosphate (GTP) serves as a switch to

turn on some proteins.

The Formation of Complex Molecular Structure

• Different types of subunits can self-assemble to form complex

structures.• One example is the tobacco mosaic virus (TMV), which was shown to

self-assemble from ribosomal subunits and proteins.

• Cells may use molecular chaperones to assemble molecularstructures.

• Some proteins can self-assemble from purified subunits.• Other proteins require molecular chaperones for proper

folding. – Molecular chaperones may protect protein structure

during the heat shock response. –

The heat shock response involves synthesis of heatshock proteins that prevent denaturation of existingproteins.

• Heat shock proteins and other chaperones prevent aggregationof denatured or newly synthesized proteins.

• Chaperones also move newly synthesized proteins acrossmembranes.

• The protein GroEL is synthesized in E. coli is essential for theproper folding of other cellular proteins.

• GroEl acts in conjunction with another protein, GroES.

• Attachment of GroES to GroEL induces a conformational change in the

GroEL protein.

• The GroEL-GroES complex assists a protein and achieving its native state.

• GroEl acts in conjunction with another protein, GroES.

•

Attachment of GroES to GroEL induces a conformational change in theGroEL protein.

• The GroEL-GroES complex assists a protein and achieving its native state.

cmb chapter 2

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