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46          SECTION II    BIOCHEmISTRY  ``BIOCHEMISTRY—CEllUlAR                                                                                                        BIOCHEmISTRY  ``BIOCHEMISTRY—CEllUlAR





                ` `BIOCHEMISTRY—CEllUlAR

               Cell cycle phases     Checkpoints control transitions between phases of cell cycle. This process is regulated by cyclins,
                                       cyclin-dependent kinases (CDKs), and tumor suppressors. M phase (shortest phase of cell cycle)
                                       includes mitosis (prophase, prometaphase, metaphase, anaphase, telophase) and cytokinesis
                                       (cytoplasm splits in two). G 1  and G 0  are of variable duration.

                REGUlATION OF CEll CYClE
                Cyclin-dependent     Constitutively expressed but inactive when not
                 kinases               bound to cyclin.
                Cyclins              Regulatory proteins that control cell cycle    G 2                  M
                                       events; phase specific; activate CDKs.                          Mitosis
                Cyclin-CDK complexes  Phosphorylate other proteins to coordinate                      Cytokinesis
                                       cell cycle progression; must be activated and
                                       inactivated at appropriate times for cell cycle
                                       to progress.                                                             G

                Tumor suppressors    p53 Ž p21 induction Ž CDK inhibition Ž Rb      DNA Synthesis           Growth  O
                                                                                        I N T E R P H A S E
                                       hypophosphorylation (activation) Ž G 1 -S                           G 1
                                      progression inhibition. Mutations in tumor      S
                                      suppressor genes can result in unrestrained
                                                                                                    Rb, p53 modulate
                                      cell division (eg, Li-Fraumeni syndrome).                     G restriction point
                                                                                                     1
                                     Growth factors (eg, insulin, PDGF, EPO, EGF)
                                      bind tyrosine kinase receptors to transition the
                                      cell from G 1  to S phase.
                CEll TYPES
                Permanent            Remain in G 0 , regenerate from stem cells.  Neurons, skeletal and cardiac muscle, RBCs.
                Stable (quiescent)   Enter G 1  from G 0  when stimulated.     Hepatocytes, lymphocytes, PCT, periosteal cells.

                Labile               Never go to G 0 , divide rapidly with a short G 1 .   Bone marrow, gut epithelium, skin, hair follicles,
                                      Most affected by chemotherapy.            germ cells.



               Rough endoplasmic     Site of synthesis of secretory (exported) proteins   Mucus-secreting goblet cells of the small
               reticulum               and of N-linked oligosaccharide addition to   intestine and antibody-secreting plasma cells
                                       lysosomal and other proteins.            are rich in RER.
                                     Nissl bodies (RER in neurons)—synthesize   Proteins within organelles (eg, ER, Golgi bodies,
                                       peptide neurotransmitters for secretion.  lysosomes) are formed in RER.
                                     Free ribosomes—unattached to any membrane;
                                       site of synthesis of cytosolic, peroxisomal, and
                                       mitochondrial proteins.



               Smooth endoplasmic    Site of steroid synthesis and detoxification of   Liver hepatocytes and steroid hormone–
               reticulum               drugs and poisons. Lacks surface ribosomes.   producing cells of the adrenal cortex and
                                       Location of glucose-6-phosphatase (last step of   gonads are rich in SER.
                                       glycogenolysis).

















          FAS1_2019_01-Biochem.indd   46                                                                                11/7/19   3:16 PM
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