Sullivan General Human Physiology Lecture 6

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Molecular Control Mechanisms

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Ligand
* any molecule/ion that binds to the surface of a binding site (protein) by other than covalent bonds
Ligand binding (due to)
1. oppositely charged ions or polarized groups
2. attractions between nonpolar regions

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Facts about LIGANDS ...

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* ligand SHAPE COMPLEMENTARY to the shape of the binding site
* binding site SPECIFIC for ion/molecule
* ligand has AFFINITY for binding site (high/tight, low/loose)
* per cent SATURATION of binding sites is related to ... (concentration of ligand, affinity, and competition)

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Almost all cell function depends on ...

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protein

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REGULATION (alteration) of protein (binding-sites) can occur in WHAT ways?

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2 Ways:

1. altering shape of binding site alters binding
2. regulating protein synthesis

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altering shape of binding site alters binding ...

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(temperature, acidity, etc.)
a. allosteric modulation
- binding of one ligand at (regulatory site) alters shape/activity at other binding site (functional site) for 2nd protein/ligand binding.
b. covalent modulation
- covalent bonding of charged groups to protein side chains alters electrical field/affinity of site
Example: protien kinases
protein + ATP ---protein kinase --> protein-PO4 + ADP
(substrate)(enzyme)(products)

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regulating protein synthesis
FACTS

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* different cells contain different proteins
* proteins are coded for in DNA
* all cells in body have identical DNA
* cells differ because only a portion of the total DNA is used by a cell for protein synthesis
* the sequence of nucleotides determines the amino acid order in a protein (primary structure)
* a gene is a portion of a DNA molecule
* human cells contain more than 30,000 - 40,000 genes
* another nucleic acid RNA is also involved in protein synthesis

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Information for protein synthesis FLOWS ...

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DNA (nucleus) ....
RNA (nucleus/cytoplasm) ...
protein (cytoplasm)

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DNA

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* double helix
* 2 polynucleotide chains
* each nucleotide contains one base
* adenine, thymine, cytosine, or guanine
* a sequence of 3 bases on DNA is called ... a CODE WORD (or TRIPLET)
* each triplet eventually codes for a particular amino acid in the protein being synthesized

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AAA
TTT
CCC
ACC
CCT

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triplets

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"redundant" in relation to DNA

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* in some cases several different triplets all code for the same amino acid

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Aside from codes for amino acids, what other codes are in DNA?

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* start code
- TAC
* termination code
- ATC, ATT, ACT

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mRNA
messenger RNA does what?

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carries the message (code) from DNA in nucleus to cytoplasm (where protein sybthesis occurs)

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what is it called when mRNA is made from DNA?

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transcription

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Transcription

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* in the DNA just ahead of the gene to be transcribed ther eis a sequence of nucleotides called the PROMOTER (only on sense strand)
* RNA POLYMERASE (enzyme) binds to the promoter (on the sense strand) catalyzing BOTH the unwinding of the DNA strand and the covalent binding of ribonucleotides in the formation of mRNA.
* RNA polymerase moves along strand causing HYDROGEN BONDS to form between DNA and complementary bases of mRNA
* mRNA formed is complementary to DNA
* a 3 base sequence in mRNA is a CODON
* NUCLEAR ENZYMES remove introns before mRNA diffuses out thru nuclear pores to cytoplasm and splice pieces back together
* designation of sequences of nucleotides as introns/exons is NOT FIXED for a given gene

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CODE WORDS or TRIPLETS vs CODONS

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CODE WORDS or TRIPLETS:
triple letter sets in DNA
CODONS:
triple letter sets in mRNA

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NOT ALL NUCLEOTIDES TRANSCRIBED ...

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into mRNA code for amino acids

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EXONS

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expression regions ... portions of nucleotides that CODE (10-25% of nucleotides)

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INTRONS

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intervening sequences... portions of nucleotides that DO NOT CODE (75-90% of nucleotides)

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Transcription allows a single piece of DNA ...

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to create more than one protein

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Translation

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* mRNA in the cytoplasm binds to a RIBOSOME (free or on ER)
* at ONE END tRNA combines with a CODON in mRNA, on the OTHER END it covalently bonds to a SPECIFIC AMINO ACID (bonding of amino acid catalyzed by aminoacyl-tRNA synthetase
* tRNA anticodon BASE PAIRS with mRNA codon (carrying with it amino acids bonded to other end of tRNA)
* PEPTIDYL TRANSFERASE (ribosomal enzyme) catalyzes the formation of PEPTIDE BONDS between the amino acids (brought by tRNA)
* after peptide bonds are formed between amino acids, tRNA is released from the ribosome (goes to get another amino acid)
* when termination codon is reached, the COMPLETED PROTEIN is released from ribosome

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what specifies the ORDER of amino acids in the protein?

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* it is the SEQUENCE OF CONDONS in mRNA that specifies the ORDER of amino acids in the protein

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tRNA

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* transfer RNA
* smallest type of RNA
* folds back on itself forming a 3 SIDED CLOVERLEAF

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anticodon

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the 3 base sequence (three letter group) in tRNA

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a ribosome is WHAT physically?

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* a ribosome is the physical structure in the cytoplasm on which proteins are synthesized

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aminoacyl-tRNA synthetase

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* aminoacyl-tRNA synthetase (enzyme) links specific amino acids to tRNA

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What do RIBOSOMES contain ...

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* ribosomes contain protein and 2 subunits of ribosomal RNA (rRNA)

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DNA Replication

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* both strands used
* entire strand replicated
* DNA polymerase
* DNA ligase

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Protein synthesis
is a process that can be regulated by:

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1. altering the rate of transcrition
2. altering combinations of exons
3. regulating stability of mRNA
4. regulating mRNA translation

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depends on protein synthesis ...

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body structure andfunction depends on protein synthesis

zygote (1 cell) -------> adult body (40 trillion cells)
many many cell divisions (mitoses)

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Mitosis

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cell division/replication
.... also involves DNA replication in a manner SIMILAR to mRNA formation needed for protein synthesis

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Mitosis is what kind of replication?

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semi-conservative replication (1/2 old and 1/2 new)

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time for cell division varies:

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... once in 24 hrs (rapidly dividing cell)
... NEVER in lifetime (muscle/nerve cells)

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Cell Cycle:

Cell Division

Notable

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* cell spends most time in interphase
* every cell in the body has the same genetic information
* cells are different because differt combinations of genes are active
* during the process of cell differetiation genes are activated or inhibited
* errors in base sequencing that occur during cell divisions are called MUTATIONS

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Mutations (can)

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1. cause no noticable change in a cells functioning
2. modify a cells functioning but still be compativle with cell growth/replication
3. lead to cell death

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Cell Cycle
* Cell Division

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1. Mitosis (nuclear division)
2. Cytokinesis (cytoplasmic division)

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Cancer

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* is a disease in which control mechanisms for cell replication do not work

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Characteristics of Cancer Cells:

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1. anaplasia
2. cell membrane changes
3. antigenic changes
4. biochemical changes
5. changes in karyotype

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Mutation causes

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* gene cloning
* recombinant DNA
* restriction enzymes