Mcb 102 Set 5

Front 1

Basic glycogen structure

Back 1

Includes non reducing ends and "reducing ends" on right

Front 2

Glycogen breakdown (discovered by?)

Back 2

•Glycogen phosphorylase discovered by Carl and Gerty Cori

•yields glucose 1-phosphate

Front 3

Two step mechanism of glycogen phosphorylase reacton

Back 3

1.The phosphate, in conjunction with PLP (Pyridoal phosphate) Phophorylated vitamin B6, donates a hydrogen and releases the glycogen. (Makes schiff base)

2. The phosphate attacks the carbocation intermediate

Front 4

How glucose-1phosphate is converted to glucose 6 phosphate w/ mechanism

Back 4

Phosphoglucomutase (generated by cleaving the 6 phosphate after phosphoglucokinase makes glucose 1,6 bisphosphate

Front 5

Glycogen breakdown in liver

Back 5

Glucose-6 phosphatase in membrane releases glucose into bloodstream

Front 6

Debranching in glycogen

Back 6

transferase and hydrolase in one polypeptide

Front 7

Glycogen synthesis

Back 7

UDP-glucose is made by UDP glucose pyrophosphoylase, glycogen synthase gives glycogen +1 residues with retention of configuration

Front 8

Branching enzyme

Back 8

•Glucose alpha 1-4 linkages yields starch, not very soluble

• Glycogen has alpha 1-6 branches and is more soluble

•branching enzyme requires 11 or more glucose residues

•removes about 7 residues and transfers them to alpha 16 linkage, more than 4 residues from the next branch

Front 9

Getting started with glycogen synthesis

Back 9

Glycogenin,

ounce primer is made, glycogen synthase takes over

Front 10

Glycogen storage dieseases

Back 10

• PT had enlarged liver full of glycogen, low blood glucose between meals, Glucose-6-phosphatase is defective (Von Gierke)

• PT's muscles cramp during vigorous exercise, blood lactate does not increase as much as in normal ppl --> defective muscle glycogen phosphorylase (McArdle), or defective PFK-1 (Tarui)

Front 11

Regulation of glycogen degradation

Back 11

Allosteric control of muscle glycogen phosphorylase

Front 12

Hormone control of glycogen phosphorylase

Back 12

•Muscle: epinephrine

•liver: glucagon

•Epiniphrine or glucagon bind to receptors

Receptor•hormone stimulates Gs-protein•GDP -->Gs-protein•GTP which stimulates adenyl cyclase, which makes cAMP PKA, which phosphorylates certain Sers (one such serine is on phosphylase-b kinase-SerOH

Front 13

Reversal of glycogen hormone cascade

Back 13

Front 14

Regulation protein phosphatase 1

Back 14

These phosphorylations must revert spontaneously

Front 15

Regulation of phosphorylase kinase by Ca++ release

Back 15

Front 16

Glycogen phosphorylase of liver as a glucose sensor

Back 16

When glucose binds to allosteric sites, the phosphorylase becomes inactive (b)

Front 17

Epinepherine hormone cascade in heart (glycolysis and glycogenolysis)

Back 17

Glycogen synthase is turned off by the hormone cascade (phorphoylated), also phosphorylated by other kinases

Front 18

Coordinate control of glycogen metabolism

Back 18

Front 19

Citric acid cycle overview (discovery)

Back 19

•O2 --> CO2 occurs in muscle but not cell extract

•Centrifugation-> occurs in mitochondria

Front 20

Lipoic acid

Back 20

in amide linkage to a lysine side chain

Front 21

Citric acid cycle cofactors overview

Back 21

Pyruvate+ NAD+ CoA

--> CO2 + acetyl-CoA _ NADH + H+

Cofactors: TPP, lipoate, NAD+, FAD, CoA

Front 22

Arsenic poisoning in citric acid cycle

Back 22

Front 23

Citrate synthase reaction mech

Back 23

1

Acetyl-CoA (enol) + Oxaloacetate (with H2O) -->

Citrate (with CoA-SH

Front 24

Aconitase reaction

Back 24

2

Iron sulfer cluster in aconitase pulls off OH- from C2 and transfers it to C3

Front 25

Isocitrate dehydrogenase reaction

Back 25

3

Loss of one CO2, coordinated by Mn2+

Front 26

alpha-ketoglutarate dehydrogenase reaction

Back 26

4

It is like pyruvate dehydrogenase reaction requiring NAD+, CoA, TPP, lipoate, FAD

Front 27

Conserved mechanism for oxidative decarboxylation

Back 27

Front 28

Succinyl-CoA synthetase reaction

Back 28

5

•converts succinyl-CoA to Succinate with GDP+ Pi to GTP and CoA-SH as a biproduct

•GTP+ ADP -->

GDP + ATP

Front 29

Succinate dehyrdogenase reaction

Back 29

6

• Succinate -->

Fumerate

•FAD oxidized to FADH2

Front 30

Fumerase reaction

Back 30

7

Has Carbanion transition state

Front 31

Malate dehydrogenase reaction

Back 31

8

Oxidizes NAD+ to NADH + H+

Front 32

Nine enzymes needed in citric acid cycle

Back 32

1 Citrate synthase 6 nucleoside

2 Aconitase diphosphate kinase

3 isocitrate 7 Succinate

dehyrdogenase dehyrdogenase

4 a-ketoglutarate 8 Fumerase

dehyrdogenase 9 malate

5 succinyl-CoA dehydrogenase

Front 33

Comprehensive citric acid cycle

Back 33

"officer can I keep selling sugar for money" =

Oxaloacetate, citrate, isocitrate, ketoglutarate, succinyl-CoA, succinate, fumerate, malate

Front 34

An asymmetric enzme...

Back 34

can bind a non-chiral compound asymetrically, they become chiral on the surface of the enzyme

•compounds of this type are called prochiral

Front 35

Why reactions of NAD+ can get H on one side or the other

Back 35

Front 36

Why is oxidation of Acetyl-CoA a cycle

Back 36

•larger intermediates are easily bound and deformed by enzme surfaces, whereas acetate would be difficult to grab and manipulate.

•Cycle allows the cell to make important molecules.

-a-ketoglutarate --> Glutamate

-oxaloacetate --> Aspartate

Front 37

origin of oxaloacetate in TCA cycle

Back 37

•produced during gluconeogenesis

• allosteric activator is acetyl-CoA, (which accumulates from breakdown of fatty acids)

Front 38

Biotin

Back 38

A vitamin

-requirement small for humans except for ppl who eat a lot of egg whites

-avidin binds to biotin to prevent bacteria growth

Front 39

Reactions that fill up the citric acid cycle

Back 39

Anaplerotic

Front 40

Reactions drain the citric acid cycle

Back 40

Cataplerotic

Front 41

Regulation of TCA

Back 41

Pyruvate dehydrogenase reaction

Front 42

Covalent modification also regulates pyruvate dehyrogenase

Back 42

Front 43

Regulation of isocitrate dehyrdogenase and communication between pathways

Back 43

Front 44

Reminder

Back 44

make notecards of involved systems to study afk

Front 45

Palmitate

Back 45

Hexadecanoic acid

Front 46

Glycerol

Back 46

Front 47

Triacyl glycerol

Back 47

6 times better than carbs at storing energy, more reduced, not hydrated,

GLY=2,500kJ, lasts for a day

Fat = 420,000kJ lasts for months

Front 48

Structure of adipocyte

Back 48

Front 49

Release of fatty acids from triacylglycerols in the adipocyte

Back 49

Front 50

1904 Franz Knoop

Back 50

Front 51

Fatty acid --> fatty acyl-CoA

Back 51

Front 52

Carnitine

Back 52

Front 53

Entry of fatty acids into mitochondria

Back 53

A carnitine acyl transferase reaction

Front 54

Acyl-carnitine/carnitine shuttle

Back 54

Front 55

ß-oxidation scheme, part 1

Back 55

Front 56

ß-oxidation scheme, part 2

Back 56

Front 57

ß-oxidation scheme, part 3

Back 57

-Entry of electrons into electron transport and oxidative phosphorylation

-FADH2--> electron transferring flavoprotein--> 1.5 ATP

-NADH--> Complex I

--> 2.5 ATP

Front 58

Regulation of fatty acid degradation and synthesis

Back 58

First step: ATP + CO2 + Acetyl-CoA carboylase --> ADP + Pi + Malonyl CA (inhibitor of carnitine acyl transferase I) ->->-> Fatty acids

Front 59

Diseases of fatty acid degradation (MCADD)

Back 59

Acyl-CoA dehydrogenases:

1 for long chains 12-18

1 for medium chains 2-14

1 for short chains 4-8

- Medium Chain AD deficiency, MCADD, Lys304Glu--> 10%SIDS --> high levels of octanoic acid in blood, dicarboxylic acids in urine

Tx: low fat, high carb diet

Front 60

Diseases of fatty acid degradation (Jamaican vomiting sickness)

Back 60

Convulsions, coma, and death caused by Unripe Aackee fruit that contains hypoglycin

Front 61

Degradation of fatty acids with odd numbers of carbons

Back 61

Front 62

Vitamin B-12

Back 62

Front 63

Arrangement at the rxn center of Vitamin B12

Back 63

Front 64

Mechanism of C and H rearrangements (B12)

Back 64

Front 65

Vitamin B12 disease

Back 65

Vitamin B12 is made by bacteria and used by people

Plants do not use B12 because it is photosensitive

People absorb B12 through intenstine by a protein called intrinsic factor, geriatrics are deficient in intrinsic factor --> get pernicious anemia, need B12 injections

Front 66

Intrinsic factor found by?

Back 66

1918 Hooper: Raw liver cures pernicious anemia in PTs

1925 Whipple: induced anemia in dogs, cured with diet of raw liver

1926 Minot and Murphy: showed that eating 1/2 lb of raw liver /day cured pernicous anemia

1936 Castle: PTs w/ Stomachs removed --> pernicious anemia, vomitus cured PTs

Front 67

Extrinsic factor

Back 67

1947 Shorb & Flokers: Factor purified from liver allows growth of bacterium on minimal salts and glucose

1956 Hodgkin: Extrinsic factor = Vitamin B12

Intrinsic factor ID'd w/ radioactive Cobalt, binds to Co, Vit B12 used by humans in methylmalonyl-Coa Mutase and methionine synthase

Front 68

Glycerol into glycolysis

Back 68

Front 69

Starvation, diabetes -->

Back 69

Accumulation of "ketone bodies"

In liver there is high [acetyl-CoA] and low [oxaloacetate]

Front 70

origin of ketone bodies (1)

Back 70

Front 71

Origin of ketone bodies 2

Back 71

ß-hydroxybutyrate travells to the brain

Front 72

ß-hydroxybutyrate as fuel in TCA cycle

Back 72

Oxaloacetate may come from protein breakdown

aspartate--> oxaloacetate

Front 73

High levels of ß-hydroxybutyrate reduce blood pH (Acidosis)

Back 73

Extreme acidosis is called ketosis which can cause coma and death, if dieting, eat some carbs to provide oxaloacetate

Front 74

Essential AAs

Back 74

V,I,L(branched chain)

F, W (aromatic)

T, H, K, M

Amino acids cannot be stored

Excess amino acids --> keto acids and are used as fuel

Front 75

AA digestion methods

Back 75

Stomach: pepsin /F/Y/W

Small intestine: trypsin K/R/

Chymotrypsin F/W/Y/

Carboxypeptidase releases AA from C-terminus

Aminopeptidase releases AAs from the N-terminase

Front 76

Enzyme catalyzed transaminations

Back 76

Front 77

Transamination mech pt. 1

Back 77

Front 78

Transamination mechanism pt. 2

Back 78

Includes nitrogen attack and schiff base

Front 79

Transamination mechanism pt. 3

Back 79

Front 80

Glutamate dehyrdogenase reaction

Back 80

Glu+NAD(P)+ + H20--> alpha-ketoglutarate + NADPH + NH4+, Driven by NH4 removal

Front 81

Delivery of amino groups to the liver for the urea cycle

Back 81

Front 82

Delivery of alanine to liver

Back 82

alanine aminotransferase

Front 83

Urea synthesis in liver stimulated by?

Back 83

Stimulted 10-fold in excess of molar amount of certain added compounds

Front 84

Overall scheme of urea cycle

Back 84

Front 85

Reactions of urea cycle

Back 85

-Carbomoyl phosphate synthetase I

-Ornithine transcarbamoylase

-Argininosuccinate

-Argininosuccinase, arginase

Front 86

Carbamoyl phosphate synthetase I

Back 86

Front 87

Ornithine transcarbamoylase

Back 87

Front 88

Arginosuccinate synthetase

Back 88

Front 89

Argininosuccinase

Back 89

Front 90

Keto-amino cycle

Back 90

Front 91

Carbamoyl phosphate synthetase I deficiency

Back 91

leads to high [NH4+] in blood. Tx: Low protein diet, alternative nitrogen excretion

Front 92

Argininosuccinate Acidemia

Back 92

argininosuccinase deficiency, argininosuccinate accumulates and is excreted Arginine is depleted

Tx: Low protein diet + arginine

Front 93

Big picture of urinary system pt. 1

Back 93

Front 94

Big picture of urinary system pt. 2

Back 94

Front 95

Diseases in converting breakdown of AA

Back 95

Alkaptonuria- black urine (recessive traits) Homogentisate accumulates, gives arthritis late in life (know mechanism?) Missing Homogentisate dioxygenase

Phenylketonuria- Urine+ Fe3+ --> olive green, PTs have high levels phenylpyruvate Tx: Low Phe diet, no aspartame (D-F-methyl-ester)

Phenylalanine is defective in PKU, Phe competes with other AAs in nerve cells

Front 96

Branched chain AAs pt 1

Back 96

Front 97

Branched chain AAs pt 2

Back 97

Front 98

Patricia Stallings case

Back 98

MMA responsible for poisoning

Tx: diet low in fatty acids with odd numbers of carbons, branched chain amino acids, and methionine

Front 99

Methionine metabolism

Back 99

Front 100

SAM donates methyl groups

Back 100

Can also donate methyls to DNA protecting it

Front 101

Regeneration of SAM

Back 101

Front 102

Degradation of methionine contributes to MMA

Back 102

Front 103

Ox Phos

Cytochrome peaks

Back 103

c types: 550nm

b types: 560nm

a types: 600nm

Front 104

order of reduction of cytochromes

Back 104

cyt b, cyt c1 cytc, cyt a, O2

Front 105

Coenzyme Q mechanism

Back 105

Front 106

Last discovered electron carriers

Back 106

Iron-sulfur centers, Oxidation states detected by EPR

Front 107

COMPLEX I

Back 107

NADH: ubiquinone oxidoreductase

NADH+5H+N+Q>NAD+ +QH2+4H+P

Front 108

COMPLEX II (succinate dehydrogenase)

Back 108

No H+ is pumped across the inner membrane. No ATP is synthesized. Mutations in Heme b allow more Q- to donate electrons to •O2 --> superoxide radical--> tumors of the head and neck (hereditary paraganglioma)

Front 109

Fatty-acyl-CoA dehydrogenase

Back 109

No pumping of H+ No ATP

Front 110

COMPLEX III (Cytochrome bc complex = Ubiquinone: cytochrome c oxidoreductase)

Back 110

Electrons will pass from QH2, a two-electron carrier to cyt c, a one-electron carrier

Front 111

Complex III and the Q cycle

Back 111

Front 112

Complex IV, Cytochrome c oxidase

Back 112

4 cyt c (red) = 8 H+(N) + O2 --> 4 cyt c (ox) + 4H+(p) + 2H2O

Front 113

F fragment ATPase

Back 113

F_1 (upper) has 3 equivalent has 3 equivalent alpha-beta units and it makes ATP F_0 (oligomycin-sensitive, lowers) pumps H+ and causes the asymmetric gamma center stalk to turn. The alpha-beta subunits of F_1 bind to ATP or ADP + Pi, or nothing

Front 114

Symporter for Pi and protons

Back 114

membrane protein that transports the species in the same direction

Front 115

Poisons for electron transport and ATP synthesis

Back 115

Rotenone (complex I)

antimycin A (complex III)

cyanide (complex IV)

oligomycin B (F-ATPase)

bongkerekic acid/ atracytlocide for adenine nucleotide translocase

Front 116

Genetic diseases of mitochondria

Back 116

hereditary paraganglioma

Leber's hereditary optical neuropathy (LHON)

myoclonic epilepsy and ragged red fiber disease (MERRF)

Creation and destruction of superoxide radicals

Front 117

Back 117

ubiquinone (coenzyme Q)

Front 118

Back 118

Glutathione (gamma-glutamyl-cysteinyl-glycine)

Front 119

2,4 dinitrophenol

Back 119

Do you know how to draw this?