�����

¥�Õ`��

Ŗůƀśƅ��

�ÛƄÕà3�

ÕžŶſƃŝ�

ŗƅūŶŒšƅ�

Šŝŭƀ�D�

œžŚŬƃü�

PGH2

PGF2α

PI4,5P2 PI3,4,5P3

IP3+DG

1I��

¥¤�]�

ÇÐ�Ca2+�q ŚŭƅŤ�]*�

ŧƃŲŜò"Z�

ÓÍ� ěTG ŝſţƂƅƀ

ùĂÓÍü�

�è�

Ŗůƀśƅ�

ÓÍÇÐ�

¥�Õ�

œŪŔŹŘŕƃ�

Óòľ!�B�Ò�

PGD2

PGE2 TXA2PGI2

HO

OH

OH

O

O

OH

OH

OO

O

O

OH

O

OH

OH

O

HO

HO

OH

OH

O

HO

O

O

OH

O

OH

O

OHHO

OH

O

Figure 15-14a Molecular Biology of the Cell (© Garland Science 2008)

��1I��

ųūĹĿƎƏ¼E;�

Figure 15-14b Molecular Biology of the Cell (© Garland Science 2008)

��1I�ľ�÷ Ƈ��]*�ƈ�

Figure 15-14c Molecular Biology of the Cell (© Garland Science 2008)

��1I�ľ�÷Ƈ�]*�ƈ�

Figure 15-37 Molecular Biology of the Cell (© Garland Science 2008)

Figure 15-38 Molecular Biology of the Cell (© Garland Science 2008)

Figure 15-63 Molecular Biology of the Cell (© Garland Science 2008)

Figure 15-21c Molecular Biology of the Cell (© Garland Science 2008)

¥¤�]Óò�

ƄČŷƂŢŧŝžƃšƃĜƂŕŞūſŖƃĜſŦſƃÓòĜetc.%ěěěěěěěěěěěěěěěě→ěGŧƃŲŜò�V<1I�ƇGPCRƈ%%ƄČŢũƂŕŬĜ]ŸƀŽƃĜŴŧŻƃDĜÏ�üĜetc.%ěěěěěěěěěěěěěěěě→ě��1I�%%ƄČŕŰŠūƅƀſƃÓòƇPI(3,4,5)P3ĜIP3ĜDAGĜetc.ƈ%�

ſƃÓò�ŞƁŢũƂƅƀ� ÄÓò�

ŢŶŔƃş�

ŻŖſƃ�

ƁŠŨƃ�ƓƔđ%

¥�ÕĺIJľ�`Óò�

Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)

�ć7ÓÍü (18:2, 20:4, 20:5, 22:6ħAĢƈ�

ć7ÓÍü (16:0, 18:0ħAĢƈ�

sn-1�� sn-2��

ſƃÓòÓÍüľĄJº]�

ŸŢŸſŲƅŤ�

ŸŢŸſŲƅŤD (PLD) �ŸŢŸſŲƅŤC

(PLC) �ŸŢŸſŲƅŤA2 (PLA2) �

ŸŢŸſŲƅŤA1 (PLA1) �

ſƃÓò�ŞƁŢũƂƅƀ�

ŢŶŔƃş�

ŻŖſƃ�

ŸŢŶŒŨšƀŞſƃ%ŸŢŶŒŨšƀŕŰŠūƅƀļĻ�

ŢũƂŕŬŸƀŽƃ ŴŧŻƃD ]ŸƀŽƃ�

��1I��

ŢŶŔƃşŠƃ Ƌſƃü�

ŷƂŢŧŝžƃšƃ ƂŕŞūſŖƃ ſŦŸŢŶŒŨšƃü�

GPCR �

šœŠƀŝſţƂƅƀ ŸŢŸŕŰŠŧŕŬ�

ÇÐ�ûÆļĻ�

¥¤�]Óòľ¦¥ĺ�§��

CH2

CH2O O P HO

CH O OH

O -

C O

O OH

O

HO HO

Figure 15-32 Molecular Biology of the Cell (© Garland Science 2008)

Figure 15-13 Molecular Biology of the Cell (© Garland Science 2008)

��1I�ľſřƃŬ�

œŢŵſƃ�

ŕƃŬżŧŠƃ�

Figure 15-30 Molecular Biology of the Cell (© Garland Science 2008)

G protein-coupled receptors (GPCRs) Ŀýåļ%Þ�´Ĺġō�

(A) GPCR-targeting drugs in top 20 (B) First-in-class drugs (after 2010)

Rank Name Disease Targets 2 Clopidogrel Thrombosis P2Y12

7 Salmeterol Asthma β2

9 Valsartan Hypertension AT1

10 Quetiapine chizophrenia D2, 5-HT2

11 Montelukast Asthma CysLT1

12 Aripiprazole chizophrenia D2, 5-HTR

18 Olanzapine chizophrenia D2, 5-HTR

20 Candesartan Hypertension AT1

World sales in 2011 (more than $4 billion) From Cegedim Strategic Data

Name Disease Targets

Fingolimod Multiple sclerosis S1P1

Mogamulizu-mab

T cell lymphoma CCR4

Lorcaserin Obesity 5-HT2C

Mirabegron Incontinence β3

Icatibant Angioedema B2

Vismodegib Cancer SMO

Ramelteon Insomnia MT1, 2

From Nat. Rev. Drug Discov. and ChEMBL databases

First-in-class Best-in-class

( ) First-in-class

First-in-class 1.4 2

First-in-class

Best-in-class

aspirin�

!

22 212 21 3

X Y

50 8-9

Recessive mutation Dominant mutation

Recessive mutation

Dominant mutation

Figure 19-26 Essential Cell Biology (© Garland Science 2010)

A

B

C

674 PANEL 19–1 Some essentials of classical genetics

TWO GENES OR ONE?Given two mutations that produce the same phenotype, how can we tell whether they are mutations in the same gene? If the mutations are recessive (as they most often are), the answer can be found by a complementation test.

In the simplest type of complementation test, an individual who is homozygous for one mutation is mated with an individual who is homozygous for the other. The phenotype of the offspring gives the answer to the question.

COMPLEMENTATION:MUTATIONS IN TWO DIFFERENT GENES

homozygous mutant mother homozygous mutant father

hybrid offspring shows normal phenotype:one normal copy of each gene is present

NONCOMPLEMENTATION:TWO INDEPENDENT MUTATIONS IN THE SAME GENE

homozygous mutant mother homozygous mutant father

hybrid offspring shows mutant phenotype:no normal copies of the mutated gene are present

GENES AND PHENOTYPES Gene: a functional unit of inheritance, usually corresponding to the segment of DNA coding for a single protein. Genome: all of an organism’s DNA sequences.

locus: the site of the gene in the genome

alleles: alternative forms of a gene Wild type: the normal,naturally occurring type

Mutant: differing from thewild type because of a geneticchange (a mutation)

GENOTYPE: the specific set of alleles forming the genome of an individual

PHENOTYPE: the visible character of the individual

allele A is dominant (relative to a); allele a is recessive (relative to A)

homozygous A/A heterozygous a/A homozygous a/a

In the example above, the phenotype of the heterozygote is the same as that of one of thehomozygotes; in cases where it is different from both, the two alleles are said to be co-dominant.

a

a

b

b

a

b

a1 a2

a2

a1

a2

a1

MEIOSIS AND GENETIC RECOMBINATION

paternal chromosome

a b

maternal chromosome

A B

diploid germ cell

genotype ABab

A b

a B

site of crossing-over

genotype Ab

haploid gametes (eggs or sperm)

MEIOSIS ANDRECOMBINATION

The greater the distance between two loci on a single chromosome, the greater is the chance that they will be separated by crossing-over occurring at a site between them. If two genes are thus reassorted in x% of gametes, they are said to be separated on a chromosome by a genetic map distance of x map units (or x centimorgans).

genotype aB

Complementation test

Forward genetics

Reverse genetics

RNA RNAimouseyeastC.elegansArabidopsisDrosophila

ES (Embryonic Stem cell)

iPS (induced pluripotent stem cells )

Figure 10-36 (part 2 of 2) Essential Cell Biology (© Garland Science 2010)

RNA RNAiNon-coding RNA

mRNA

2006

RNA RNAi

!CRISPR Cas9

CRISPR Cas9

��������������

(Bioinforma*cs). .

v� áDNAâ CCTAGTCCATG.....��x�,�

MHáq â

mRNA CCUAGUCCAUG.....��x�,�

MHá^kâ

¿Þ˵pMAGNVKKSSGA.....«ÓÉzx�,�

�

¿Þ˵p>`,�!|f«ÓÉz,��

T<t,��

Äà¿Ðà»áDBâ�

p~�8/c�

DNAÀÁÏ Ò­µÜ«Û­�

X[�NMR <ti8/c� �L�eßi8/c�

DNA��x�B"/c�

v� DB GenBank, DDBJ, ……

¿Þ˵pDB

Swiss-Prot, PIR, …… ¿Þ˵p>`w�DB

Prosite, Plam, ……. ¿Þ˵p>`DB

PDB, SCCP, CATH, ……. 3GDB

PubMed, MEDLINE, Scopus, ….

x�Ar�ÑÖܺà:W

BLAST, FASTA, ……..

v� áDNAâ CCTAGTCCATG.....��x�,�

MHáq â

mRNA CCUAGUCCAUG.....��x�,�

MHá^kâ

¿Þ˵pMAGNVKKSSGA.....«ÓÉzx�,�

�

¿Þ˵p>`,�!|f«ÓÉz,��

T<t,��

Äà¿Ðà»áDBâ�v� DB

GenBank, DDBJ, …… ¿Þ˵pDB

Swiss-Prot, PIR, …… ¿Þ˵p>`w�DB

Prosite, Plam, ……. ¿Þ˵p>`DB

PDB, SCCP, CATH, ……. 3GDB

PubMed, MEDLINE, Scopus, ….

x�Ar�ÑÖܺà:W

BLAST, FASTA, …….. SNP DB �

v� ��áSNPâ,��

aF%¿Þ˵pP��KÄà¿Ðà»�

ß���x��¥«ÓÉz�,�©(���!! !→�9zã«ÓÉzx�i8¾ÍÅ®¯«!

!ß���x�ã«ÓÉzx��,��¥�x�,�©(���!

! !→�BLAST!(Basic!Local!Alignment!Search!Tool)!!ß�¿Þ˵p«ÓÉz�>`���§,�©(���!

! !→�PubMed!(3G:W)!!ß�QS_�;\©m §!

! !→�Scopus!(3G:W) �

atggcaaggaggagctcg?ccagtcgtgtcagataatatccctg?cac??gccg?ggagtcaatatctgc?agga?cactgcacatcgaa?aagagagcagaaggatgggaggaaggtcctcctacagtgctatcagactccccctggaccaacatctccggatc?gcaagggcaggtgc?tgaac?caagaggctggacctcctca?gtcgctgtgacaac?gtgtaagagctataccag?gctgccatgac?tgatgagctgtg?tgaagacagcccgtggctgggagtgtactaaggacagatgtggagaagtcagaaatgaagaaaatgcctgtcactgctcagaggactgc?ggccaggggagactgctgtaccaa?accaagtgg?tgcaaaggagagtcgca?ggg?gatgatgactgtgaggaaataaaggccgcagaatgccctgcaggg?tg?cgccctcca?aatcatc?ctccgtggatggc?ccgtgcatcatacatgaagaaaggcagcaaagtcatgcctaata?gaaaaactaaggtc?gtggcacacactctccctacatgaggccggtgtacccaactaaaacc?tcctaac?atacac?tggccactgggctatatccagaatcacatggaa?g?ggcaa?caatgtatgatcctgta?tgatgccac??catctgcgagggcgagagaaa?taatcatagatggtggggaggtcaaccgctatgga?acagccaccaagcaaggggtgaaagctggaaca?c??ggtctg?gtcatccctcacgagcggagaata?aaccata?gcagtggctcaccctgccagatcatgagaggcc?cggtctatgcc?cta?ctgagcaacctga?tctctggacacaaatatggccc?tcggccctgagatgacaaatcctctgagggaaatcgacaaaa?gtggggcaa?aatggatggactgaaacaactaaaactgcatcggtgtgtcaacgtcatc?tgtcggagaccatggaatggaagatgtcacatgtgatagaactgag?c?gagtaa?acctaactaatgtggatgata?ac?tagtgcctggaactctaggaagaa?cgatccaaa?tagcaacaatgctaaatatgaccccaaagcca?a?gccaatctcacgtgtaaaaaaccagatcagcac?taagcc?ac?gaaacagcacc?cccaaacg?tgcactatgccaacaacagaagaa?gaggatatcca?ta?ggtggaacgcagatggcatg?gcaaggaaacc?tggatg?tataagaaaccatcaggaaaatgc??tccagggagaccacgga?tgataacaaggtcaacagcatgcagactg??tgtagg?atggcccaaca?taagtacaagactaaagtgcctcca?tgaaaaca?gaac?tacaatg?atgtgtgatctcctggga?gaagccagctcctaataatgggacccatggaag?tgaatcatctcctgcgcactaatacc?caggccaaccatgccagaggaag?accagacccaa?atccaggga?atgtacc?cagtctga??gacctgggctgcac?gtgatgataaggtagagccaaagaacaag?ggatgaactcaacaaacggc?catacaaaagggtctacagaagagagacacctcctctatgggcgacctgcagtgc?tatcggactagatatgatatc?atatcacactgac?tgaaagtgg?atagtgaaata?cctaatgccactctggacatcatatactg?tccaaacaggctgagg?tccaggg?cctgaccatctgaccag?gcgtccggcctgatgtccgtg?tctccgag?tcagtcagaactg?tggcctacaaaaatgataagcagatgtcctacgga?cctc?tcctcc?atctgagctc?caccagaggctaaatatgatgca?cc?gtaaccaatatggctccaatgtatcctgc?tcaaacgggtctggaa?a?tccaaagggta?ggtgaagaaatatgc?cggaaagaaatggag?aacgtgataagtggaccaatc?cgactatgactatgatggc?acatgacacagaagacaaaataaaacagtacgtggaaggcag?cca?cctg?ccaactcactaccacagcatcatcaccagctgtctgga?tcactcagcctgccgacaagtgtgacggccctctctctgtgtcctcc?catcctgcctcaccggcctgacaacgaggagagctgcaatagctcagaggacgaatcaaaatgggtagaagaactcatgaagatgcacacagctagggtgcgtgaca?gaacatctcaccagcctggac?c?ccgaaagaccagccgcagctacccagaaatcctgacactcaagacatacctgcatacatatgagagcgaga?taac?tctgagcatctgcagtacagtc?atcaactgg?gtata??tata?g??tgta?ta?aa?tgaaaccaggaca?aaaaatg?agta??aatcctgtacc�

·ÉÔ�,����§��x���§�

����§��x��¥��7K�,�©(�����ä�