biochem_mod2

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soren101
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biochem_mod2
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2010-10-02 22:27:38
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biochem ms1 mod2
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biochem mod2 ms1
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  1. WHAT ARE THE MAJOR COMPONENTS OF BIOLOGICAL MEMBRANES?
    • LIPIDS: AMPHYPATHIC
    • CHOLESTEROL
    • SPHINGOLIPIDS - SPINGOMYELIN (SP), GANGLIOSIDES
    • GLYCEROL PHOSPHOLIPIDS - PHOSPHATIDYLCHOLINE (PC), PE, PG, PS, PI, CL

    • PROTEIN:
    • INTEGRAL
    • PERIPHERAL

    • CARBOHYDRATE: NEVER FREE
    • GLYGOPROTEIN
    • GLYCOLIPID
  2. GENERALIZED STRUCTURE AND FUNCTION OF BIOLOGICAL MEMBRANES?
    • MICELLES:
    • SMALL <20 nm
    • SINGLE HYDROPHOBIC TAIL

    • LIPID BILAYERS:
    • LARGE
    • 2 FATTY ACYL CHAINS
    • NON-COVALENT INTERACTIONS
    • HYDROPHOBIC INTERACTIONS ARE PRIMARY FORCE, ALSO VDW & ELECSTAT
  3. STRUCTURE AND FUNCTION OF LIPOSOMES?
    • LIPID BILAYER ~50 nm
    • USED TO GET WATER SOLUBLE DRUGS PAST MEMBRANE AND INTO CELLS
    • INCORPORATE INTO MEMBRANES, DIRECT DELIVERY BYPASSES CIRCULATION AND DIGESTION
  4. PROTEINS WITHIN LIPID BILAYERS
    SPAN MEMBRANES WITH ALPHA HELICES (HYDROPHOBIC AAs)

    • CHANNEL PROTEINS FORMED BY BETA SHEETS (PORIN)
    • HYDROPHOBIC AAs ON OUTSIDE
    • HYDROPHILIC AAs ON INSIDE

    • INTEGRAL MEMBRANES DO NOT HAVE TO SPAN ENTIRE BILAYER
    • PROSTAGLANDIN H2 SYNTHASE-1 --> ARACHIDONIC ACID. ASPRIN INHIBITS
  5. CLINICAL CORRELATION OF IONOPHORES?
    DRUGS USED TO DISRUPT IONIC GRADIENTS IN INVADING MICROORGANISMS

    SMALL MOLECULES THAT SURROUND IONS AND SHUTTLE THEM ACROSS MEMBRANES

    ex. VALINOMYCIN BINDS K+
  6. 6 BASIC CONCEPTS OF PROTEIN BIOSYNTHESIS?
    1) DNA TRANSCRIBED INTO RNA WHICH IS TRANSLATED INTO PROTEIN

    2) mRNA IS READ 1 CODON (3 NUCLEOTIDES) AT A TIME BEGINNING WITH AUG (METHIONINE) AND ENDING WITH STOP CODON (UAA, UAG, UGA)

    3) READ 5' TO 3' AND PROT IS SYNTHESIZED FROM N TO C TERMINUS

    4) mRNA UPSTREAM OS START CODON CALLED 5' UNTRANSLATED REGION (UTR) AND DOWNSTREAM CALLED 3' UTR. 5' CAP AND POLY-A TAIL

    5) SEQUENCE BEGINNING WITH START CODON AND ENDING WITH STOP CALLED (ORF). EUK USUALLY HAVE ONLY 1 ORF BUT USES POST-TRANSLATIONAL PROCESSING TO MAKE SEVERAL PROTEINS

    6) BASIC COMPONENTS OF TRANSLATION ARE THE RIBOSOME AND tRNA
  7. SIX BASIC FEATURES OF GENETIC CODE?
    1) CODON = 3 NUCLEOTIDE RESIDUES

    2) 64 CODONS: 61 FOR AAs AND 3 STOPS

    • 3) DEGENERATE: MORE THAN 1 CODON FOR SPECIFIC AA
    • MORE THAN 1 tRNA FOR GIVEN AA
    • DIFFERENT tRNA CARRIES INITIATOR METHIONINE (tRNAiMET) THAN METHIONINES FOR REST OF ORF

    4) SPECIFIC: EACH CODON SPECIFIES ONLY 1 AA

    5) ALMOST UNIVERSAL IN ALL ORGANISMS

    6) EACH NUCLEOTIDE IS PART OF ONLY 1 CODON AND ORF IS READ CONTINUOUSLY WITHOUT PUNCTUATION
  8. WHAT IS THE AMINOACYL-tRNA SYNTHETASE REACTION?
    ACTIVATION OF AAs

    AA-tRNAs CATALYZE COVALENT LINKING OF EACH AA TO ITS tRNA

    20 OF THESE ENZYMES; ONE FOR EACH AA

    ANTICODON AND PROOFREADING ABILITY OF SYNTHETASE ENSURES SPECIFICITY

    ATP DRIVES REACTION

    AA + ATP + AA-tRNAs -------> AA-AMP + PPi + tRNA ------> AA-tRNA + AMP
  9. INITIATION IN PROCs


    SPECIAL tRNA DIRECTS ADDITION OF FORMYL GROUP (H-C=O) ONTO METHIONINE FROM N10-FTHF

    3 IFs (1, 2, 3) CATALYZE FORMATION OF PRE-INITIATION COMPLEX THAT INCLUDES fMET~tRNA, mRNA, AND GTP

    ANTICODON IN FIRST tRNA HYDROGEN BONDS TO AUG

    SHINE-DELGARNO SEQUENCE (AGGAGG ON mRNA) H-BONDS WITH COMPLEMENTARY 16S rRNA WITHIN 30S SUBUNIT

    GTP HYDROLYZED, IFs RELEASE, 50S SUBUNIT JOINS FORMING THE INITIATION COMPLEX

    fMET-tRNA MOVED TO P SITE OF 70S SUBUNIT
  10. STEPS IN EUK INITIATION OF TRANSLATION (5)
    1) SPECIAL tRNA LIKE IN PROK, BUT MET IS NOT FORMYLATED. MET-tRNA BINDS WITH GTP AND eIF-2 FORMING TERNARY COMPLEX

    2) FORMATION OF INITIATOR tRNA-RIBOSOME COMPLEX. MET-tRNA-eIF-2-GTP BINDS WITH 40S SUBUNIT CONTAINING MORE eIFs

    3) mRNA BINDS TO INITIATION COMPLEX. eIF-4 BINDS TO CAP SITE AT 5' END OF mRNA RESULTING IN BINDING OF eIF-4A & B. NOW 40S PRE-INITIATION COMPLEX

    4) FORMATION OF 80S INITIATION COMPLEX. 40S MOVES ALONG 5'UTR UNTIL ENCOUNTERS FIRST AUG (PROCESS CALLED SCANNING; PROKS JUST USE S-D SEQUENCE). GTP HYDROLYZED, BOUND IFs RELEASED ALLOWING 60S TO JOIN. MET-tRNA IN P SITE

    5) RECYCLING OF eIF-2. eIF-2-GDP CONVERTED BACK TO eIF-2-GTP BY eIF-2B. eIF-2B REQUIRED AND IS A TARGET FOR REGULATION
  11. HEMIN EFFECT
    REGULATION OF eIF-2 ACTIVITY

    SYNTHESIS OF GLOBIN CHAIN IS INHIBITED IN THE ABSENCE OF HEME

    INHIBITION ACHIEVED BY ACTIVATION OF PROTEIN KINASE WHICH PHOSPHORYLATES eIF-2, PREVENTING INITIATION OF PROTEIN SYNTHESIS

    IRON ANEMIA SYMPTOMS: EXTREME FATIGUE, SHORTNESS OF BREATH, HEADACHES, DIZZINESS, INFECTION, ARRHYTHMIA
  12. INTERFERON EFFECT
    SMALL PROTEINS WITH ANTI-VIRAL & ANTI-CANCER PROPERTIES

    PHOSPHORYLATES eIF-2 WHICH INACTIVATES PROTEIN BIOSYNTHESIS

    ACTIVATES ENDONUCLEASE THAT DEGRADES mRNA

  13. EUK VS. PROK INITIATION (PIC)


  14. ELONGATION IN PROKS
    EF-Tu AND EF-G

    EUK EF-1 & 2 CORRESPOND TO PROK EF-Tu AND EF-R
  15. ELONGATION IN EUK
    • PLACEMENT OF AA-tRNA:
    • EF-1 ALPHA BINGS NEXT AA-tRNA AND MOVES INTO A-SITE OF RIBOSOME

    GTP HYDROLYZED TO BIND AA-tRNA ONTO A-SITE; EF-1 ALPHA-GDP COMPLEX RELEASED

    EF-1 BETA GAMMA CATALYZES RECYCLING OG EF-1 ALPHA-GDP TO FORM EF-1 ALPHA-GTP IN PREPATATION TO PARTICIPATE IN THE NEXT CYCLE

    • PEPTIDE BOND FORMATION:
    • OCCURS BETWEEN CARBOXYL GROUP OF FIRST AA AND AMINO GROUP OF AA AT THE A-SITE, FORMING A DIPEPTIDE-tRNA WHICH REMAINS AT THE A-SITE

    FORMATION OF BOND CATALYZED BY PEPTIDYLE TRANSGERASE, A RIBOSOME COMPONENT

    • MOVEMENT OF PEPTIDYL-tRNA FROM A-SITE TO P-SITE:
    • EF-2-GTP COMPLEX BINDS TO RIBOSOME AND STIMULATES TRANSLOCATION OF DIPEPTIDYL-tRNA FROM A TO P-SITE

    RIBOSOME MOVES SO THAT NEXT CODON IS ALIGNED WITH A-SITE

    EMPTY OR DEACYLATED tRNA MOVES TO E-SITE

    GTP IS HYDROLYZED TO GDP AND EF-2-GDP COMPLEX IS RELEASED

    REPEAT

  16. TERMINATION
  17. DRUGS THAT INHIBIT EUK TRANSLATION
    • CYCLOHEXIMIDE
    • ELONGATION

    • RICIN
    • TRANSLATION - MULTIPLE SITES

    • PUROMYCIN: BOTH EUK & PROK
    • PEPTIDE TRANSFER
    • RESEMBLES 3' END OF AA-tRNA AND LACKS REACTIVE CORBONYL GROUP
    • COMPETES FOR A-SITE
  18. DRUGS THAT INHIBIT PROK TRANSLATION
    • ERYTHROMYCIN
    • TRANSLOCATION

    • NEOMYCIN
    • TRANSLATION - MULTIPLE SITES

    • STREPTOMYCIN
    • INITIATION; ELONGATION
    • RESEMBLES F-fMET-tRNA AND COMPETES FOR RIBOSOME

    • TETRACYCLIN
    • AA-tRNA BINDING

    • PUROMYCIN: BOTH EUK & PROK
    • PEPTIDE TRANSFER
    • RESEMBLES 3' END OF AA-tRNA AND LACKS REACTIVE CORBONYL GROUP
    • COMPETES FOR A-SITE
  19. DIPTHERIA
    CORYNEBACTERIUM DIPTHERIAE SECRETES TOXIN CONTAINING ENZYME THAT ENTERS CELLS. ENZYME CATALYSES REACTION LINKING ADP RIBOSE TO EF-2, THUS INHIBITING PROTEIN SYNTHESIS.

    FEVER, COUGHING, BREATHING PROBLEMS, DIFFICULTY SWALLOWING, BLOODY NOSE

    GIVE IM OR IV ANTITOXIN AND FOLLOW WITH PENICILLIN AND/OR ERYTHROMYCIN

    eEF-R TRANSFERES PEPTIDYL-tRNA FROM A-SITE TO P-SITE
  20. STEPS IN PROTEIN TARGETING
    1) TRANSLATION OF SIGNAL PEPTIDE OR SIGNAL SEQUENCE AT EH AMINO TERMINUS

    2) SIGNAL RECOGNITION PARTICLE (SRP), A PROTEIN-RNA COMPLEX, RECOGNIZES SIGNAL SEQUENCE

    3) SRP DIRECTS POLYRIBOSOME TO ER AND INTERACTS WITH DOCKING PROTEIN

    4) TRANSLATING POLYRIBOSOME CONTINUES TO SYNTHESIZE PROTEIN WHICH WILL ENTER THE LUMEN OF MEMBRANE, WHILE RIBOSOME RECEPTOR WHICH IS LOCATED IN THE ER MEMBRANE WILL MAINTAIN THE POLYSOME DOCKED AT THE ER MEMBRANE

    5) SIGNAL PEPTIDE REMOVED BY SIGNAL PEPTIDASE. THUS, SECRETED PROTEINS AND THOSE PRESENT IN TE MEMBRANE OR ORGANELLES DO NOT HAVE SAME AMINO TERMINUS AS mRNA CODING SEQUENCE

    6) PROTEIN INSIDE ER PACKAGED WITHIN SECRETORY VESICLE AND MOVED TO GOLGI

    7) EXTENSIVE MODIFICATION OF PROTEINS CAN OCCUR IN ER, GOLGI, AND TRANSPORT VESICLES. PROTEINS TARGETED TO THE LYSOSOMES REQUIRE ADDITIONAL MODIFICATIONS.

    8) PROTEINS DESTINED FOR SECRETION END UP IN SECRETORY VESICLES THAT FUSE WITH PLASMA MEMBRANE AND EMPTY CONTENTS OUTSIDE CELL

    9) PROTEINS DESTINED TO RESIDE IN PLASMA MEMBRANE END UP IN VESICLES THAT FUSE WITH PLAMA MEMBRANE, BUT MAINTAIN THE PROTEIN IN MEMBRANE

    10) ENZYMES TRAVELING TO LYSOSOMES ACQUIRE MANNOSE-6-PHOSPHATE THAT ARE RECOGNIZED BY M-6-P RECEPTOR. M-6-P RESIDUES ASSIST IN TARGETING THESE PROTEINS WITHIN THEIR VESICLES TO THE LYSOSOMES
  21. I CELL DISEASE (MUCOLIPIDOSIS II)
    DISORDER OF PROTEIN TARGETING - INCLUSION BODIES

    DEFICIENCY IN GlcNAc-1-P-TRANSFERASE ENZYME LEADING TO AN ABSENCE OF MANOSE-6-PHOSPHATE RESIDUES ON SEVERAL LYSOSOMAL ENZYMES

    LYSOSOMAL PROTEINS ARE NOT DELIVERED FROM THE GOLGI TO THE LYSOSOMES

    LYSOSOMAL ENZYMES WHICH NORMALLY DEGRADE WASTE PROTEINS IN THE LYSOSOME ARE SECRETED FROM THE CELL, RESULTING IN INCREASE IN SERUM LEVELS OF ENZYME. SECRETED ENZYMES GET DEGRADED.

    ON OTHER HAND, CELLS DO NOT DEGRADE WASTE PRODUCTS IN THEIR LYSOSOMES, LEADING TO BUILD-UP OF INCLUSION BODIES (I-CELLS)
  22. ACETYLATION
    POST-TRANSCRIPTIONAL MODIFICATION

    ADDITION TO HISTONES CHANGES INTERACTION WITH DNA (RELEASES)

    GENE ACTIVATION

    APL
  23. CARBOXUGLUTAMATION
    POST TRANSCRIPTIONAL MODIFICATION

    BLOOD CLOTTING PROPERTIES, INCLUDING PROTHROMBIN AND FACTOR X

    CONVERSION OF GLUTAMIC ACID TO GAMMA-CARBOXYGLUTAMIC ACID

    GAMMA-CGA RESIDUES NECESSARY FOR THESE PROTEINS TO BIND

    HEMOPHILIA
  24. GLYCOSYLATION
    POST-TRANSCRIPTIONAL MODIFICATION

    LINKS CARBOHYDRATES AND PROTEINS TO MAKE GLYCOPROTEINS

    CONTROLS TRANSFER OF PROTEINS FROM ROUGH ER TO GOLGI AND SECRETORY VESICLES

    CYSTIC FIBROSIS - AUTOSOMAL RECESSIVE

    ELECTROLYTE TRANSPORT IN LUNG, PANCREASE, AND LIVER DEFECTIVE CAUSING THICK MUCOUS SECRETION LEADING TO CHRONIC OBSTRUCTIVE LUNG DISEASE AND PERSISTENT INFECTION

    MEMBRANE GLYCOPROTEIN, CF TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) NOT PROPERLY GLYCOSYLATED DUE TO DELETION OF 3 NUCLEOTIDES CODING FOR PHE 508, CAUSING PROTEIN MISFOLDING AND DEGRADATION WITHIN PROTEOSOMES
  25. HYDROXYLATION
    POST-TRANSCRIPTIONAL MODIFICATION

    SPECIFIC PROLINE AND LYSINE RESIDUES IN COLLAGEN, RESULTING IN STABILIZATION OF COLLAGEN MOLECULE
  26. METHYLATION
    POST-TRANSCRIPTIONAL MODIFICATION

    HISTONES
  27. PHOSPHORYLATION
    POST-TRANSCRITIONAL MODIFICATION

    HISTONES AND NUMEROUS PTOTEINS/ENZYMES
  28. PRENYLAITON
    POST-TRANSCRIPTIONAL MODIFICATION

    ADDITION OF A PRENYL GROUP ANCHORS THE PROTEIN ONTO CELL MEMBRANES
  29. CHAPERONS
    ASSIST IN PROTEIN FOLDING

    MIS/UNFOLDED PROTEINS TEND TO AGGREGATE AND MAY BECOME EITHER RESISTANT OR SUSEPTIBLE TO DEGRADATION

    NEURODEGENERATIVE DISORDERS: CDJ, ALZ, HD
  30. CLINICAL ASPECT OF PROTEIN CLEAVAGE
    INSULIN MADE BY CLEAVAGE OF PREPROINSULIN

    FAMILIAL HYPERPROINSULINEMIA - EQUAL AMOUNTS OF INSULIN AND ABNORMAL PROINSULIN RELEASED INTO CIRCULATION. NEITHER DIABETIC NOR HYPOGLYCEMIC

    DEFICIENCY IN PROCESSING ENZYMES OR MUTATION IN CLEAVAGE SITE OF PROINSULIN
  31. GLUCOSE TRANSPORTERS (5)
    GLUT1 - ALL MAMMALIAN TISSUES. BASAL GLUCOSE UPTAKE

    GLUT2 - LIVER AND PANCREATIC BETA CELLS. IN PANC REGULATES INSULIN, IN LIVER REMOVES EXCESS GLUCOSE FROM BLOOD

    GLUT3 - ALL MAMMALIA TISSUES. BASAL GLUCOSE UPTAKE

    GLUT4 - MUSCLE AND FAT CELLS. AMOUNT IN MUSCLE PLASMA MEMBRANE

    GLUT5 - SMALL INTESTINE. INC IN ENDURANCE TRAINING; PRIMARILY A FRUCTOSE TRANSPORTER
  32. ROLE OF GLYCOLYSIS IN LIVER
    ENERGY SOURCE

    PROVIDES LIPID PRECURSORS

    FIRST GLYCOLYTIC REACTION IS ALSO FIRST STEP IN GLYCOGEN SYNTHESIS
  33. ROLE OF GLUCOSE IN MUSCLE
    ENERGY

    FIRST REACTION NEEDED FOR FIRST STEP IN GLYCOGEN SYNTHESIS
  34. ROLE OF GLUCOSE IN ADIPOSE TISSUE
    ENERGY

    LIPID PRECURSER
  35. ROLE OF GLUCOSE IN BRAIN
    ALMOST ABSOLUTE REQUIREMENT FOR ENERGY

    LIPID PRECURSOR
  36. ROLE OF GLUCOSE IN RBC's
    ABSOLUTE REQUIREMENT FOR ENERGY
  37. DIETARY CARBOHYDRATES
    STARCH FROM PLANTS AND GLYCOGEN FROM ANIMALS

    SALIVARY AND PANCREATIC ALPHA-AMYLASE DEGRADE CARBS INTO DISACCHARIDES MALTOSE, ISOMALTOSE, AND LARGER MALTOTRIOSE, AND LIMIT DEXTRINS

    SMALL INTESTINE BRUSH BORDER ENZYMES LACTASE, SUCRASE, AND GLUCOSIDASES DEGRADE MONOSACCHARIDES INTO GLUCOSE, GALACTOSE, AND FRUCTOSE
  38. HOW IS FRUCTOSE ABSORBED?
    FRUCTOSE IS HIGHER IN LUMEN THAN ENTEROCYTE, AND HIGHER IN ENTEROCYTE THAN BLOOD

    PASSIVELY TRANSPORTED BY GLUT5 (INTO ENTEROCYTE) AND GLUT2 (INTO BLOOD)
  39. HOW ARE GLUCOSE AND GALACTOSE ABSORBED?
    CONCENTRATIONS ARE LOWER IN LUMEN

    RELY ON SGLT1 (SODIUM GLUCOSE TRANSPORTER 1) AND USES Na GRADIENT

    GRADIENT MAINTAINED BY Na/K PUMP ON THE CAPILARY SIDE OF MEMBRANE

    THEN PASSIVELY TRANSPORTED INTO BLOOD BY GLUT2
  40. STAGE 1 OF GLYCOLYSIS
    GLUCOSE + HEXOKINASE + ATP --> GLUCOSE-6-PHOSPHATE

    GLUCOSE-6-PHOSPHATE + PHOSPHOGLUCOSE ISOMERASE --> FRUCTOSE-6-PHOSPHATE

    FRUCTOSE-6-PHOSPHATE + PHOSPHOFRUCTOKINASE + ATP --> FRUCTOSE 1,6 BISPHOSPHATE
  41. STAGE 2 OF GLYCOLYSIS
    FRUCTOSE 1,6 BISPHOSPHATE + ALDOLASE --> GLYCERALDYHIDE-3-PHOSPHATE (GAP) OR DIHYDROXYACETONE PHOSPHATE (DHAP)

    TRIOSEPHOSPHATE ISOMERASE INTERCONVERTS DHAP AND GAP
  42. STAGE 3 OF GLYCOLYSIS
    GLYCERALDEHYDE-3-PHOSPHATE (GAP) + GAP DEHYDROGENASE + NAD + Pi --> 1,3 BISPHOSPHOGLYCERATE (1,3 BPG) + NADH + H

    1,3 BPG + PHOSPHOGLYCERATE KINASE + ADP --> 3-PHOSPHOGLYCERATE + ATP

    3-PHOSPHOGLYCERATE + PHOSPHOGLYCERATE MUTASE --> 2-PHOSPHOGLYCERATE

    2-PHOSPHOGLYCERATE + ENOLASE --> PHOSPHENOLPYRUVATE

    PHOSPHENOLPYRUVATE + PYRUVATE KINASE + ADP --> PYRUVATE + ATP
  43. REGULATION OF GLUCOSE TRANSPORTERS IN GLYCOLYSIS
    ADIPOSE AND MUSCLE USE GLUT4 WHICH IS STIMULATED BY INSULIN, THUS INCREASING INTRACELLULAR GLUCOSE AND INCREASING GLYCOLYSIS
  44. REGULATION OF GLUCOSE PHOSPHORYLATION IN GLYCOLYSIS
    1) HEXOKINASE IS INHIBITED BY GLUCOSE-6PHOSPHATE (NEGATIVE FEEDBACK)

    ex IF PFK-1 AND/OR PYRUVATE KINASE ARE INHIBITED THEN GLUCOSE-6-PHOSPHATE IN MUSCLE WILL INCREASE AND INHIBIT HEXOKINASE AND GLUCOSE UTILIZATION.

    OCCURS UNDER FASTING CONDITIONS. FATTY ACIDS OR KETONE BODY OXIDATION USED FOR ENERGY SO GLUCOSE SPARED FOR RBC's

    2) GLUCOKINASE IN LIVER PHOSPHORYLATES GLUCOSE WHEN BLOOD [ ] IS HIGH

    WHEN [ ] REDUCED, PHOSPHORYLATION IN LIVER WILL DECLINE AND GLUCOSE UTILIZATION DECLINES. SPARED FOR RBC's

    GK HAS LOWER AFFINITY FOR GLUCOSE THAN HEXOKINASE

    LIVER GK IS ACTIVATED BY GLUCOSE - MOVES GK FROM INACTIVE NUCLEAR POOL TO CYTOSOL WHEN [ ] IS HIGH

    LIVER GK INDUCED BY INSULIN
  45. REGULATION OF PFK-1 IN GLYCOLYSIS
    PFK-1 IS RATE LIMITING STEP IN GLYCOLYSIS

    1) ALLOSTERICALLY INHIBITED BY ATP, CITRATE, AND PROTONS MEANING ENERGY NEEDS ARE MET

    USED FOR FED AND FASTING STATE. IN FED STATE, SLOWS GLUCOSE UTILIZATION WHICH PREVENTS EXCESS FAT PRODUCTION. IN FASTING STATE, ATP AND CITRATE INCREASED DUE TO FATTY ACID OXIDATION AND TISSUES LIKE LIVER AND MUSCLE DON'T NEED GLUCOSE, THUS SPARED FOR RBC'S

    2) ALLOSTERICALLY ACTIVATED BY AMP MEANING ENERGY NEEDS ARE NOT MET

    ACTIVATED BY F2,6-P2 - IMPORTANT REGULATOR BECAUSE PRODUCTION IS HORMONALLY REGULATED. IN FASTING STATE, GLUCAGON DECREASES PRODUCTION OF F2,6-P2 CAUSING INHIBITION OF LIVER GLYCOLYSIS. GLUCAGON ACTIVATES ADENYLATE CYCLASE, WHICH PRODUCES cAMP WHICH DECREASES F2,6-P2 WHICH INHIBITS GLYCOLYSIS

    F2,6-P2 REGULATED BY DUAL ENZYME. WHEN PHOSPHORYLATED (FASTING, GLUCAGON) F2,6-P2 IS DECREASED AND VIS VERSA (FED, INSULIN) WHEN KINASE ACTIVITY IS ACTIVATED. OPPOSITE IN MUSCLE (EPINEPHRINE)
  46. REGULATION OF PYRUVATE KINASE IN GLYCOLYSIS
    PK INHIBITED BY ATP AND ALANINE IN LIVER AND MUSCLE (ENERGY NEEDS MET BY FATTY ACIDS AND GLUCONEOGENESIS IS UNDERWAY). SPARE GLUCOSE FOR RBC's

    IN LIVER NOT MUSCLE, PK IS PHOSPHORYLATED AND INACTIVATED BY PKA WHEN BLOOD GLUCOSE IS LOW. PKA ACTIVATED BY cAMP. WHEN BLOOD GLUCOSE IS HIGH, INSULIN STIMULATES A PHOSPHATASE THAT DEPHOSPHORYLATES PK AND ACTIVATES IT.
  47. ROLE OF GLYCOLYSIS IN GENERATING 2,3-BISPHOSPHOGLYCERATE IN RBC's
    RBC's REQUIRE 2,3-BPG TO REGULATE OXYGEN BINDING TO HEMOGLOBIN

    1,3-BPG + 2,3-BPG MUTASE --> 2,3-BPG

    2,3-BPG + 2,3-BPG PHOSPHATASE --> 3-PHOSPHOGLYCERATE

    SIDESTEP OF GLYCOLYSIS PATHWAY BYPASSES ATP-GENERATING STEP
  48. ENTRY OF FRUCTOSE INTO GLYCOLYTIC PATHWAY
    PRESENT IN INCREASING AMOUNTS IN WESTERN DIET

    LIVER POSSESSES SPECIFIC FRUCTOSE-PHOSPHORYLATING ENZYME FRUCTOKINASE WHICH GENERATES FRUCTOSE 1-PHOSPHATE. LIVER FRUCTOLYSIS BYPASSES REGULATED PFK-1 STEP CAUSING UNDESIRED CONSEQUENCES
  49. ENTRY OF GALACTOSE INTO GLYCOLYSIS
    GALACTOSE + GALACTOKINASE --> GALACTOSE 1-PHOSPHATE

    GAL 1-PHOS + GAL 1-PHOS URIDYL TRANSFERASE + UDP-GLUCOSE --> UDP GALACTOSE

    UDP-GAL + GLUCOSE 1-PHOS --> UDP GLUCOSE

    GLUCOSE 1-PHOSPHATE + PHOSPHOGLUCOMUTASE --> GLUCOSE 6-PHOSPHATE
  50. ENTRY OF GLYCEROL INTO GLYCOLYSIS
    GLYCEROL + GLYCEROL KINASE --> GLYCEROL PHOSPHATE

    GLYCEROL PHOSPHATE + GLYCEROL PHOS DEHYDROGENASE --> DHAP
  51. DISORDERS IN HEXOSE METABOLISM (ANEMIA)
    PYRUVATE KINASE DEFICIENCY IMPACT RBC's
  52. DISORDERS IN HEXOSE METABOLISM (WARBURG PHENOM)
    • TUMOR CELLS PREFER GLUCOSE AND USE HYPOXIA INDUCIBLE FACTORS (HIF) TO INCREASE
    • GLYCOLYSIS.

    BLOCKING THIS EFFECT WILL LEAD TO SUPPRESSION
  53. DISORDERS IN HEXOSE METABOLISM (GALACTOKINASE AND/OR GAL 1-PHOS URIDYL TRANSFERASE)
    DEFICIENT GK RESULTIS IN ACCUMULATION OF GALACTOSE IN BLOOD (GALACTOSEMIA). ALDOSE CONVERTS TO GALACTITOL, WHICH IS OSMOTICALLY ACTIVE AND DAMAGES EYES LEADING TO CATARACTS

    • DEFICIENT URIDYL TRANSFERASE CAUSES ACCUMULATION OF GAL 1-PHOS WHICH IS TOXIC.
    • FAILURE TO THRIVE, LIVER DAMAGE, CATARACTS, AND MENTAL IMPAIRMENT

    AVOIDING GALACTOSE HELPS, BUT IF DEFICIENT UT THEN MENTAL IMPAIRMENT STILL SEEN
  54. DISORDERS IN HEXOSE METABOLISM (FRUCTOSE INTOLERANCE)
    DEFICIENCY OF ALDOSE B

    BLOCKS METABOLISM OF FRUCTOSE 1-PHOS (F1-P) AND ACCUMULATION TIES UP Pi DECREASING LEVELS OF ATP

    DEGRADATION OF AMP CAN WORSEN GOUT

    F1-P PROMOTES GLYCOLYSIS IN LIVER, AND HIGH [ ] IS TOXIC CAUSING LIVER DAMAGE/FAILURE AND THUS HYPOGLYCEMIA
  55. DISORDERS IN HEXOSE METABOLISM (FRUCTOSE TOXICITY)
    FRUCTOSE BYPASSES PFK-1 REGULATION

    LARGE AMOUNTS LEAD TO FAT

    F1-P ACCUMULATES LEADING TO ALDOLASE B DEFICIENCY (INCREASED GLYCOLYSIS)
  56. THE FED STATE
    MEET IMMEDIATE ENERGY AND BIOSYNTHETIC NEEDS & STORE THE REST FOR LATER

    PANCREAS (BCELLS) --> INSULIN --> GLUCOSE IN LIVER TO GLYCOGEN (GLYCOGENESIS) AND TO PYRUVATE (GLYCOLYSIS) --> FAT (LIPOGENESIS)

    • LIVER GLUCOSE --> BRAIN
    • --> ADIPOSE TISSUE
    • --> MUSCLE (MAY STORE AS GLYCOGEN)
    • --> RBC's

    AMINO ACIDS IN LIVER --> PROTEIN AND PYRUVATE. AA's ALSO RELEASED TO ALL TISSUES FOR PROTEIN SYNTH

    LACTATE FROM MUSCLES AND RBC's RETURN TO LIVER AND CONVERTED BACK TO PYRUVATE

    CHYLOMICRONS FROM GUT (TAGs + PROTEINS) --> LYMPHATICS --> TISSUES --> GLYCEROL + FREE FATTY ACIDS (FFAs) --> ACETYL CoA (BETA OXIDATION) IN MUSCLE
  57. THE EARLY FASTING STATE
    CALL ON ENERGY STORES TO MEET NEEDS esp BRAIN AND RBCs

    PANCREAS --> GLUCAGON --> LIVER --> GLYCOGEN --> GLUCOSE --> BRAIN, RBCs, MUSCLE

    CORI CYCLE. RBCs AND MUSCLE --> LACTATE --> LIVER --> GLUCOSE (GLUCONEOGENESIS)--> TISSUES

    ALANINE CYCLE. PROTEINS IN MUSCLE --> ALANINE --> LIVER (GLUCONEOGENESIS)

    LIVER GLYCOGEN DEPLETED IN A FEW HOURS --> "OVERNIGHT FAST"
  58. THE LATE FASTING STATE
    GLUCONEOGENESIS IS ENERGY SOURCE FOR BRAIN & RBCs

    CORI AND ALANINE CYCLES CONTINUE

    ADIPOSE --> TAGs --> FFA (LIPOLYSIS) --> LIVER --> FATTY ACIDS BETA OXIDATION

    GLYCEROL ALSO RELEASED BY TAGs --> LIVER --> GLUCONEOGENESIS

    LIVER PROTEIN BROKEN DOWN --> LACTATE & AAs --> GLUCOSE (GLUCONEOGENESIS)

    MUSCLE PROTEOLYSIS --> GLUTAMINE --> NUCLEOTIDE SYNTH FOR RAPIDLY DIVIDING CELLS --> ALANINE --> LIVER (GLUCONEOGENESIS)

    TCA CYLE BACKS UP --> ACETYL CoA CONVERTED INTO KETONE BODIES (KETOGENESIS) --> BRAIN & MUSCLE. SPARE GLUCOSE FOR RBCs
  59. /\G
    <0, EXERGONIC & SPONTANEOUS

    >0, ENDERGONIC & NON-SPONTANEOUS

    /\G = /\G^ + RTLn (PROD/REACT)

    /\G^ = -RTLn(Keq)

    • Keq: IF > 1, /\G^ IS NEGATIVE
    • IF < 1, /\G^ IS POSITIVE
  60. SYNTHESIS OF INSULIN AND ITS SECRETION
    SYNTHED AS PREPRO-PEPTIDE. PRE OR SIGNAL SEQUENCCE CLEACED IN ER

    CONNECTING OF C-PEPTIDE REMOVED BY PROTEASE THAT CLEACE AT PAIRS OF BASIC AAs AS PRO-INSULIN IS PROCESSED

    MATURE INSULIN STORED IN SECRETORY VESICLES WITH C-PEPTIDE AND AAs

    ALL RELEASED WHEN GLUCOSE [ ] GOES UP

    • SECRETION:
    • 1) GLUC TRANSPORTED INTO BETA CELL BY GLUT2 AND PHOSPHORYLATED BY GLUCOKINASE. BOTH RESPOND TP CHANGES IN BLOOD GLUCOSE [ ] BECAUSE THEIR Km (Kd FOR RECEPTOR) ARE IN RANGE OF [ ] AFTER A MEAL

    2) GLUCOSE METABOLISM INCREASES ATP LEVELS

    3) ATP CLOSES A K+ CHANNEL

    4) RESULTS IN OPENING OF VOLT-SENSITIVE Ca++ CHANNEL

    5) Ca++ ENTERS CELL AND ACTIVATES KINASES WHICH PHOSPHORYLATE PROTEINS LEADING TO INSULIN RELEASE
  61. INSULIN SIGNALING AND METABOLIC EFFECTS
    EFFECTS MANY TISSUES, MAINLY LIVER, ADIPOSE, AND SKELETAL MUSCLE

    BINDS TO SURFACE RECEPTOR AND STIMS TYROSINE PHOSPHORYLATION OF THE RECEPTOR (AUTOPHOSING TYROSINE KINASE)

    CAUSES TYROSINE PHOS OF TWO TYPES OF PROTEINS: INSULIN RECEPTOR SUBSTRATES (IRS) AND Shc (ACTIVATES Ras-MAP KINASE PATHWAY: MITOGEN ACTIVATED PROTEIN KINASE PATHWAY REGULATES GENERAL GENE EXPRESSION)

    IRS BINDS AND ACTIVATES PHOSPHATIDYLINOSITOL 3-KINASE (PI3-KINASE)

    PI3-KINASE HAS 110 CATALYTIC SUBUNIT AND 85 REGULATORY UNIT. REG UNIT BINDS PHOSPHOTYROSINE RESIDUES OF IRS RESULTING IN ACT AT CAT SUBUNIT, WHICH MAKES INOSITOL LIPIDS, WHICH ACTIVATE ENZYMES, WHICH REGULATES METABOLIC PATHWAYS

    OF THESE, Akt INC MOVEMENT OF GLUT4 GLUC TRANSPORTERS TO SURFACE OF ADIPOSE AND MUSCLE CELLS

    ALSO ACTIVATES PHOSPHATASE PP-1 WHICH DEPHOSES METABOLIC ENZYMES, WHICH ACTS OR DEACTS ENZYMES

    GSK-3 INHIBITED BY INSULIN, WHICH BLOCKS GLYCOGEN SYNTHESIS
  62. TARGET ORGANS AND METABOLIC EFFECTS OF INSULIN
    LIVER: INC GLYCOLYSIS, FATTY ACID & TAG SYNTH, VLDL RELEASE, GLYCOGEN SYNTH, AND PROTEIN SYNTH. DEC GLUCONEOGENESIS, FATTY ACID OXIDATION, AND GLYCOGEN BREAKDOWN

    ADIPOSE: INC GLYCOLYSIS, FATTY ACID AND TAG SYNTH, TAG UPTAKE FROM CHYLOMICRONS AND VLDL. DEC TAG HYDROLYSIS

    MUSCLE: INC GLYCOLYSIS, GLYCOGEN SYNTH, AND PROTEIN SYNTH. DEC GLYCOGEN
  63. GLUCAGON SIGNALING AND METABOLIC EFFECTS
    DEC BLOOD GLUCOSE DEC INSULIN AND INC GLUCAGON SECRETION

    RELEASED FROM ALPHA PANC CELLS AND TARGETS LIVER AND ADIPOSE. NO GLUCAGON RECEPTORS IN MUSCLE

    GLUCAGON RECEPTOR IS A G-PROTEIN COUPLED RECEPTOR (USES GTP similar to how myosin uses atp)

    WHEN GLUCAGON ATTACHES, GDP --> GTP AND ADENYLIL CYCLASE ACTIVATED, WHICH CONVERTS ATP TO cAMP

    cAMP ACTIVATES PKA WHICH PHOSES METABOLIC ENZYMES AND TRANSCRIPTION FACTOR cAMP RESPONSE ELEMENT BINDING PROTEIN (CREB), WHICH REGULATES METABOLIC ENZYME GENES.
  64. METABOLIC EFFECTS OF GLUCAGON
    LIVER: INC GLUCONEOGENESIS, GLYCOGENOLYSIS, FATTY ACID OXIDATION. DEC GLYCOLYSIS, GLYCOGEN SYNTH, AND FATTY ACID SYNTH

    ADIPOSE: INC TAG HYDROLYSIS
  65. METABOLIC EFFECTS OF EPINEPHRINE
    INC STRESS RELEASES CORTISOL WHICH LEADS TO EPI RELEASE

    LIVER AND ADIPOSE: SAME AS GLUCAGON THOUGH ACTS ON DIFFERENT RECEPTOR

    MUSCLE: INC GLYCOGENOLYSIS AND GLYCOLYSIS. DEC GLYCOGEN SYNTH
  66. METABOLIC EFFECTS OF CORTISOL
    STEROID THAT PASSES THROUGH LIPED BILAYER AND BINDS TO TRANSCRIPTION FACTOR RECEPTOR

    MAINLY INC GLUCOSE [ ] BY INC GLUCONEOGENESIS USING PRIMARILY AAs AND GLYCEROL (THINK ADDISON'S DISEASE)

    REGULATES GENES FOR METABOLIC ENZYMES

    LIVER: INC GLUCONEOGENESIS

    ADIPOSE: INC TAG HYDROLYSIS

    MUSCLE: INC PROTEOLYSIS
  67. PYRUVATE DEHYDROGENASE REACTION
    • PRODUCE ACETYL CoA FROM PYRUVATE
    • GLUCOSE --> PYRUVATE --> OXIDATIVE PHOSPHORYLATION --> ACETYL CoA

    REACTIONS BY 3 SEPARATE SUBUNITS (PYRUVATE DEHYDROGENASE COMPLEX (PDH))

    PYRUVATE DEHYDROGENASE --> DIHYDROLIPOYL TRANSACETYLASE --> DIHYDROLIPOYL DEHYDROGENASE

    PD REMOVES CO2 AND TRANSFERS CARBON CHAIN TO THIAMINE PYROPHOSPHATE (TPP)

    PD AND DT OXIDIZE INTERMEDIATE TO ACETATE MOIETY AND TRANSFER TO LIPOMIDE, MAKING ACETATE PORTION REACTIVE WITH CoA SO DT CAN MAKE ACETYL CoA

    OXIDIZE LIPOAMIDE FOR ANOTHER ROUND BY DD --> REDUCE FAD TO FADH2 --> NADH
  68. POINTS ABOUT TCA CYCLE
    1) NEVER HAVE GLUCONEOGENESIS FROM ACETYL CoA

    2) 1 GTP GENERATED BY SUBSTRATE LEVEL PHOS

    3) NADH PRODUCED IN 3 REACTIONS; FADH2 IN 1

    4) ALPHA-KETOGLUTARATE DEHYDROGENASE REACTION SAME AS PYRUVATE DEHYDROGENASE

    5) MALATE DEHYDROGENASE REACTION FAVORS REVERSE DIRECTION, SO RAPID DEC OF PRODUCTS (OAA AND NADH) USED TO DRIVE FORWARD
  69. PNEMONIC FOR TCA INTERMEDIATES
    • Cindy (citrate)
    • Is (isocitrate)
    • Kinky (alpha-ketoglutarte)
    • So (succyinal CoA )
    • She (succinate)
    • F*** (fumarate)
    • More (malate)
    • Often (oxalate)
  70. FADH2 is generated from Succiante to Fumarate..
    Fumarate starts with an F.
  71. OTHER USES FOR TCA INTERMEDIATES (5)
    CITRATE --> FATTY ACID AND STEROL SYNTH

    ALPHA-KETOGLUTARATE --> AA SYNTH --> NEUROTRANSMITTERS

    SUCC CoA --> HEME SYNTH

    MALATE --> GLUCONEOGENESIS

    OAA --> AA SYNTH
  72. PNEMONIC FOR TCA ENZYMES
    • CINDY (citrate synthase --> citrate)
    • AND (aconitase --> isocitrate)
    • IZZY (isocitrate dehyd --> oxalosuccinate)
    • INTIMATELY (isocitrate dehyd --> alpha-ketogluterate)
    • ADVERTISE (alpha-keto dehyd --> succ coa
    • SENSUAL (succ coa synth --> succ
    • SEX (succ dehyd --> fumarate)
    • FOR (fumarase --> malate)
    • MONEY (malate dehyd --> oaa)
  73. CARBONS ENTERING TCA CYCLE
    ALPHA-KETOGLUTERATE <-- GLUTAMATE <-- AAs

    SUCC CoA <-- PROPIONYL CoA <-- VALINE AND ISOLEUCINE

    FUMARATE <-- AAs

    OAA <-- ASPARTATE

    AAs --> PYRUVATE --> OAA & ACETYL CoA
  74. REGULATION OF PDH AND THE TCA CYCLE
    PDH AND TCA INHIBITED WHEN ENERGY CHARGE INSIDE CELL IS HIGH

    ALLOSTERIC MODULATION -- PHOS INACTIVATES PDH

    CALCIUM (+) (THINK MUSCLE CONTRACTION)

    INSULIN (+) PDH IN ADIPOSE FOR de novo FATTY ACID SYNTH

    EPINEPHRINE (+) PDH IN MUSCLE

    NADH & ACETYL CoA (-) PDH

    SUCC CoA (-) CITRATE SYNTH

    ATP (-) AND ADP (+) ACONITASE

    Ca++ (+), NADH, SUCC CoA, AND GTP (-) ALPHA-KETO DEHYD
  75. ARSENITE
    INHIBITS TRANS-ACETYLASE SUBUNIT OF PDH AND ALPHA-KDH BY FORMING ADDUCT WITH LIPOAMIDE.

    TREAT WITH BRITISH ANTI-LEWISITE (BAL)
  76. THIAMINE DEFICIENCY
    LOWERS ACIVITY OF PDH AND ALPHA-KDH SUBUNITS

    LEADS TO BERI-BERI

    IMPACTS NERVOUS SYSTEM; Severe lethargy and fatigue, together with complications affecting the cardiovascular, muscular, and gastrointestinal systems.
  77. GENETIC DEFICIENCIES IN PDH AND ITS ACTIVATING PHOSPHATASE
    RELY ON GLYCOLYSIS ENDING IN LACTIC ACID DUE TO INABILITY OF OXIDIZE PYRUVATE

    LACTIC ACIDOSIS

    NEURO DEFECTS (NO GLUCOSE FOR BRAIN)

    TREAT: GENERATE KETONE BODIES IN LIVER (BRAIN AND MUSCLE CAN USE). KETOGENIC DIET HIGH IN PROTEIN AND FAT
  78. emf
    THE FORCE THAT DRIVES THE ELECTRON FLOW

    MEASURED IN VOLTS

    OXIDATION-REDUCTION POTENTIAL IS THE FACILITY WITH WHICH AN ELECTRON DONOR (REDUCTANT) GIVES UP ELECTRONS TO THE ACCEPTOR (OXIDENT)
  79. CALCULATE FREE ENERGY CHANGE FOR REDOX REACTION
    /\G = -nF/\E

    OR

    /\G* = -nF/\E*

    n = # ELECTRONS TRANFERED

    E = REDUCTION POTENTIAL IN VOLTS

    F = 23

    THE MORE NEGATIVE THE E*, THE GREATER THE TENDENCY TO LOSE ELECTRONS (STRONG REDUCTANT). GETS OXIDIZED. MORE POSITIVE = ACCEPT ELECTRONS (STRONG OXIDANT)
  80. PROPERTIES OF MITOCHONDRIAL MEMBRANES
    OUTER - PERMIABLE TO ANIONS AND SMALL MOLECULES

    INNER - IMPERMIABLE TO EVERYTHING; CONTAINS INNER MATRIX WHERE ATP GENERATED. PROTEIN COMPLEXES OF ELECT TRANS CHAIN AND ATP SYNTHASE LOCATED IN INNER MEMBRANE. NADH ACCEPTED BY ETC IN MATRIX OR FROM FLAVOPROTEINS IN MEMBRANE

    INTERMEMBRANE SPACE - BETWEEN INNER AND OUTER
  81. 6 COMPONENTS OF ETC
    COMP I (NAPDH DEHYD) - NADPH BINDS TO FMN AND PASSES 2 e- TO IT; 2 PROTONS FORCED INTO INTERMEMBRANE SPACE. THEN PASSES 2 e- TO IRON-SULFUR CLUSTERS FORCING 4 PROTONS INTO INTERMEM.

    COENZ Q - PASSES 2 e- TO COMPLEX III AND MORE e- TRANSPORTED

    • COMP III --> Cyt C --> COMP IV (CYT OXIDASE) AND MORE e- TRANSPORTED.
    • COMP IV HAS 2 COMPLEXES IN ORDER TO REDUCE O2 (NEED 4 e-, 4 H+ TO COMPLETE)

    COMP II (SUCC DEHYD) - NO PROTONS TRANSLOCATED. e- --> UQ (COENZ Q) --> COMP III
  82. STEPS IN ATP SYNTHASE
    PROTONS DRIVEN THROUGH C RING CAUSING ROTATION OF GAMMA SUBUNIT

    ROTATION CHANGES T STATE (BOUND ATP) TO O STATE AND ATP IS RELEASED

    MEANWHILE, L FORM WITH ADP AND Pi IS CONVERTED TO T STATE (ADP --> ATP)

    SUBUNIT IN O STATE CONVERTED TO L STATE WHICH BINDS ADP AND Pi
  83. RESPIRATORY CONTROL
    REGULATES RATE AT WHICH ENERGY IS REMOVED FROM PROTON GRADIENT IN MITOCHONDRIA.

    CONTROLLED BY ADP CONCENTRATION

    ELECTRON TRANSPORT CANNOT PROCEED IF PROTONS ARE NOT PUMPED INTO INTERMEMBRANE SPACE, SO IN ORDER TO KEEP SYSTEM FROM LOCKING UP, GRADIENT IS DISIPATED TO KEEP ETC GOING.
  84. SUBSTRATE SHUTTLES IN MITOCHONDRIAL MEMBRANE
    • GLYCEROPHOSPHATE SHUTTLE:
    • 2 e- FROM CYTOSOLIC NADH --> DIHYDROACETONE PHOSPHATE --> GLYCEROL 3-PHOSPHATE WHICH CROSSES OUTER MITO-MEMBRANE --> FLAVOPROTEIN DEHYD --> FADH --> ETC --> 1.5 ATP

    • MALATE-ASPARTATE SHUTTLE:
    • CYTOSOLIC NADH REDUCES OXALOACETATE TO MALATE WHICH ENTERS MITO-MATRIX USING MALATE/ALPHA-KETOGLUTERATE. MALATE OXIDIZED BACK TO OXALOACETATE AND NADH --> ETC --> 2.5 ATP
  85. ETC INHIBITORS
    ROTENONE - INSECTICIDE THAT INHIBITS COMP I

    ANTIMYCIN A AND MYXOTHIAZOLE - NON-COMPETITIVE INHIBITS COMP III

    CYANIDE AND AZIDE - REVERSIBLE INHIBITORS OF COMP IV

    MALONATE - COMP II COMPETITIVE INHIBITOR (SUCC DEHYD)
  86. UNCOUPLERS OF ETC
    RATE OF ET CAN NO LONGER BE REGULATED BY CHEMOSTATIC GRADIENT

    FCCP

    DNP

    DISSIPATE PROTON GRADIENT (FAT SOLUABLE SO GRAB PROTONS AND DIFFUSE ACROSS MEMBRANE)

    • PATHOLOGICAL UNCOUPLERS:
    • SALICYLATE - DEGRATIVE PRODUCT OF ASPRIN
  87. ATPase INHIBITORS
    OLIGOMYCIN - BLOCKS PROTON CHANNEL

    TREAT WITH UNCOUPLERS
  88. P:O RATIO
    AMOUNT OF ADP ADDED TO THE AMOUNT OF O2 CONSUMED

    ALSO INDICATES NUMBER OF ATP MADE PER PAIR OF e-

    • NADH = 2.5
    • FADH = 1.5
  89. MITOCHONDRIAL GENETIC DISORDERS
    KEARNS-SAYRE SYNDROME

    MYCLONUS EPILEPSY WITH RAGGED-RED FIBERS (MERRF)

    LEBER'S HEREDITARY OPTIC NEUROPATHY (LHON)

    MITO ENCEPHALOPATHY LACTIC ACIDOSIS WITH STROKE-LIKE EPISODES (MELAS)

    MUSCLE WEAKNESS, HEART FAILURE/ RYTHM DISTURBANCES, DEMENTIA, MOVEMENT DISORDERS, STROK-LIKE DISORDERS, DEAFNESS, BLINDNESS, VOMITING, SEIZURES
  90. ROLE OF THE PENTOSE PHOSPHATE PATHWAY
    AKA HEXOSE MONOPHOSPHATE SHUNT

    PROVIDES NADPH

    PROVIDES 5-CARBON SUGARS

    • REACTIONS REQUIRING NADPH:
    • FATTY ACID BIOSYNTHESIS
    • CHOLESTEROL BIOSYNTHESIS
    • NT
    • NUCLEOTIDE
  91. TISSUES WITH ACTIVE PENTOSE PHOSPHATE PATHWAYS
    ADRENAL GLAND - STEROID SYNTHESIS

    LIVER - FATTY ACID, CHOL SYNTH

    TESTES - STEROID

    ADIPOSE - FATTY ACID SYNTH

    OVARY - STEROID SYNTH

    MAMMARY GLAND - FATTY ACID SYNTH

    RBC - MAINTENANCE OF REDUCED GLUTATHIONE
  92. FIRST 3 REACTIONS OF PENTOSE PHOSPHATE PATHWAY
    • GLUCOSE-6-PHOS + G-6-P DEHYD --> 6-PHOSPHOGLUCONO-GAMMA-LACTONE + NADPH
    • RATE LIMITING STEP; INDUCED BY INSULIN

    6-PG-g-L + LACTONASE --> 6-PHOSPHO-GLUCONATE

    6-PG + 6PG-DEHYD --> RIBULOSE 5-PHOSPHATE (NUCLEOTIDE SYNTHESIS)+ NADPH

    3,4,5,7 CARBON INTERMEDIATES

    ENDS IN FRUCTOSE-6-PHOS AND GLYCERALDEHYDE-3-PHOS (GLYCOLYTIC INTERMEDIATES

    BERI-BERI - TRANSKETOLASE USES THIAMINE PYROPHOSPHATE AS CO-FACTOR (INHIBITED)
  93. GLUCOSE 6-PHOSPHATE DEHYDROGENASE DEFICIENCY IN PENTOSE PHOS PATHWAY
    LACK OF NADPH LEADS TO INCREASED HYDROXYL FREE RADICAL AND OXIDATIVE DAMAGE

    CANNOT REDUCE GLUTATHIONE

    HEMOGLOBIN MOST SENSITIVE - HEMOLYTIC ANEMIA IF ENVIR OXIDANTS PRESENT. PLUS SIDE, SOME RESISTANCE TO MALARIA
  94. SITES AND PURPOSES OF GLUCONEOGENESIS
    SYNTH OF GLUCOSE FROM NON-CARB PRECURSORS (LACTATE, PYRUVATE, SOME AAs, GLYCEROL)

    LIVER AND LESSER EXTENT KIDNEY

    PROVIDE GLUCOSE TO RBC, BRAIN, SKEL MUSCLE
  95. 4 UNIQUE ENZYMES FOR GLUCONEOGENESIS
    • 1) PYRUVATE CARBOXYLASE
    • 2) PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK)
    • THESE 2 ENZYMES CONVERT PYRUVATE TO PEP

    • 3) F-1-6-BTASE CONVERTS F1-6B TO F6-B
    • 4) GLUCOSE 6-PHOSPHATASE CONVERTS G6-P TO GLUCOSE (NON-GLUCONEOGENESIS TISSUES (LACK THIS ENZYME)

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