Metabolism

Front 1

Adenosine 5' Triphosphate (ATP)

Back 1

Store of free energy within the cell. The bonds bewteen phosphates in ATP are high energy bonds because their hydrolysis is accompanied by a relative large decrease in free energy.

Front 2

Glycolysis

Back 2

Initial stage in the breakdown of glucose. can happen in the absence of oxygen and provide all energy for anaerobic organisms.
1. One ATP is used to phosphorylate glucose to glucose-6-phosphate
2. This is converted to fructose-6-phosphate
3. Another ATP is used to make fructose-1,6-biphosphate
2. Glucose is broken down into pyruvate with net gain of two molecules of ATP

Front 3

Hexokinase

Back 3

Catalyzes the initial phosphorylation of glucose and conversion to glucose-6-phosphate.

Front 4

Phosphofructokinase

Back 4

Converts fructose-6-phosphate to fructose-1,6-biphosphate. This enzyme is the key control element. It is inhibited by ATP which results in excess glucose-6-phosphate that inhibits hexokinase.

Front 5

Cleavage of fructose-1,6-biphosphate

Back 5

Yields two molecules of the three-carbon sugar glyceraldehyde-3-phosphate

Front 6

Fate of glyceraldehyde-3-phosphate

Back 6

Oxidized to 1,3-biphosphoglycerate

Front 7

Fate of 1,3-biphosphoglycerate

Back 7

High energy phosphate group is used to drive synthesis of ATP from ADP and in the process changed to 3-phosphoglycerate

Front 8

Fate of 3-phosphoglycerate

Back 8

Converted to phosphoenolpyruvate another high energy intermediate.

Front 9

Fate of phosphoenolpyruvate

Back 9

Is converted to pyruvate in a process that converts another ADP to ATP

Front 10

Total ATP in Glycolysis

Back 10

4 ATP results from conversion of glucose into 2 three carbon pyruvates. Two of these are consumed in the reaction resulting in 2 net ATP.

Front 11

NAD+

Back 11

Coenzyme that acts as a oxidizing agent and accepts electrons from glyceraldehyde-3-phosphate.

Front 12

NADH in anaerobic conditions

Back 12

Is reoxidized to NAD+ by conversion of pyruvate to lactate

Front 13

NADH in aerobic conditions

Back 13

Serves as a source of energy by donating electrons to electron transport chain where they are used to reduce O2 to H2O coupled with generation of ATP.

Front 14

Coenzyme A

Back 14

Serves as a carrier of acyl groups in various metabolic reactions. Is found in the mitochondria where pyruvate is converted to CO2 and H2O.

Front 15

Acetyl CoA

Back 15

One carbon of pyruvate is released as CO2 and the other two are added to CoA to form this also reducing one molecule of NAD+ to NADH.

Front 16

Citric acid cycle (Krebs cycle)

Back 16

Central pathway in oxidative metabolism.

Front 17

Fate of acetyl CoA

Back 17

Combines with oxaloacetate (four carbons) to yield citrate (six carbons)

Front 18

Fate of Citrate

Back 18

Eight further reactions yields two CO2 and regeneration of oxaloacetate forming one GTP which is used to drive synthesis of one ATP.

Front 19

Products of Citric acid cycle

Back 19

Three molecules of NADH and one molecule of reduced flavin adenine dinucleotide. Total ATP from TCA is 2 molecules.

Front 20

Oxidative phosphorylation

Back 20

Electrons of NADH and FADH2 combine with O2 and release energy driving synthesis of ATP from ADP.

Front 21

Electron transport chain

Back 21

Process takes place gradually by passage of electrons through a series of carriers in the inner mitochondrial membrane of eukaryotic cells.

Front 22

ATP generated per NADH

Back 22

Approximately 2.5 ATP

Front 23

ATP generated per FADH2

Back 23

Approximately 1.5 ATP (enters at a lower energy level)

Front 24

Breakdown of nucleotides for energy

Back 24

Can be broken down to sugars which then entery glycolysis

Front 25

Break down of amino acids for energy

Back 25

Can be broken down in citric acid cycle

Front 26

Break down of lipids for energy

Back 26

More efficient storage. First broken down the glycerol and free fatty acids. each fatty acid is joined to coenzyme A yielding a fatty acyl-CoA at the cost of one ATP. Fatty acids are then degraded in stepwise oxidative process, two carbons at a time and releasing one NADH and one FADH2 per oxidation. Acetyl CoA enters citric acid cycle and finishes.

Front 27

Electron Transport Chain

Back 27

To be harvested in a usable form energy must be produced gradually by the passage of electrons through a series of carriers. Organized into four complexes with a fifth complex coupling energy yielding reactions to ATP synthesis.

Front 28

Coenzyme Q (ubiquinone)

Back 28

Small, lipid-soluble molecule that carries electrons from complex I to complex III.

Front 29

Cytochrome c

Back 29

A peripheral membrane protein bound to outer face of inner membrane which carries electrons to complex IV (cytochrome oxidase)

Front 30

Cytochrome oxidase

Back 30

Location of electrons transferred to O2

Front 31

Chemiosmotic coupling

Back 31

ATP is generated by the use of energy stored in the form of proton gradients across biological membranes, rather than by direct chemical transfer of high-energy groups

Front 32

Electrochemical gradient

Back 32

pH and electric potential drive protons back into the matrix from the cytosol

Front 33

ATP synthase (F1F0 ATPase)

Back 33

Uses the electrochemical gradient to convert ATP.

Front 34

Pyruvate Dehydrogenase Complex (PDH)

Back 34

Key regulatory enzyme that converts pyruvate to AcetylCoA releasing one NADH. It is irreversible under physiological conditions because of large negative energy.
Components:
8 trimers of lipoamide reductase-transacetylase
6 dimers of dihydrolipoyl dehydrogenase
12 dimers of pyruvate decarboxylase
1. Thiamin pyrophosphate (B1, thiamin)
2. Lipoic acid
3. Flavin Adenine Dinucleotide (FAD, B2, riboflavin)
4. Nicotinamide adenine dinucleotide (NAD, B3, niacin)

Front 35

Key regulatory enzymes of the TCA cycle

Back 35

1. Citrate synthase
2. Isocitrate dehydrogenase
3. alpha-ketogluterate

Front 36

Substrate level phosphorylation in TCA cycle

Back 36

1 GTP generated from succinyl CoA. The other from NAD and FAD in oxidative phosphorylation.

Front 37

Total Yield of TCA cycle

Back 37

3 NADH, 1 FADH, 1 GTP, 12.5 ATP/pyruvate or 10 ATP/AcetylCoA

Front 38

Pyruvate carboxylase

Back 38

Uses biotin, B7 to drive pyruvate conversion to oxaloacetate stimulated by Acetyl CoA to replace intermediates used in TCA.

Front 39

Citrate Synthase

Back 39

Converts oxaloacetate to citrate.

Front 40

Isocitrate dehydrogenase

Back 40

Converts isocitrate to alpha-ketoglutarate releasing NADH and CO2.

Front 41

Alpha-ketoglutarate dehydrogenase

Back 41

Converts alpha-ketoglutarate to succinyl CoA releasing an NADH and CO2.

Front 42

Regulation of TCA cycle

Back 42

1. Signal metabolites
a. AMP like signals activate
b. ATP like signals inhibit
2. Regulatory phosphorylations
a. PDH complex -P is active
b. PDH complex +P is inactive
3. Cofactor cycling
a. NAD and FAD must be available to move reaction forward so can be a regulating step

Front 43

Complex I

Back 43

NADH dehydrogenase/NADH oxidase - mediates the transfer of electrons from NADH to the membrane-mobile cofactors, ubiquinone (coenzyme Q)

Front 44

Complex II

Back 44

Succinate dehydrogenase. Receives electrons from TCA cycle intermediate, succinate that are transferred to FADH2 and then to coenzyme Q and then continues down pathway

Front 45

Complex III

Back 45

Cytochrome b-c1 reductase. Reduces the membrane-mobile cytochrome c.

Front 46

Complex IV

Back 46

Cytochrome c oxidase. Reduced cytochrome c is oxidized by oxygen.

Front 47

Semiquinone intermediates

Back 47

Electron carriers such as CoQ and flavin mononucleotide FMN that can accept or donate one electron at a time can form these to scavenge free radicals.

Front 48

Superoxide anion radicals

Back 48

Oxygen radicals that escape the mitochondria before they are fully reduced to water

Front 49

Reactive oxygen species

Back 49

Can cause damage to DNA and proteins
1. Hydrogen peroxide
2. Hydroxyl radicals

Front 50

Enzymes that detoxify ROS

Back 50

1. Superoxide dismutase
2. Glutathione peroxidoes

Front 51

Nicotinamine Adenine Dinucleotide

Back 51

NAD+ (oxidized) and NADH (reduced) take electrons from pyruvate and transfer them to electron transport chain. Important component is Vitamin B3, niacin

Front 52

Pellagra

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Deficiency in niacin, vitamin B 3 needed for NAD action. Results in GI, skin, neurological symptoms.

Front 53

Thiamin pyrophosphate

Back 53

Involved in decarboxylating pyruvate. Needs Vitamin B1.

Front 54

Beriberi

Back 54

Deficiency in vitamin B 1 leading to GI symptoms and neurological symptoms.

Front 55

Lipoic acid

Back 55

A cofactor involved in acetyl group transfer to CoASH. Transfers electrons to riboflavin.

Front 56

Flavin Adenine Dinucleotide

Back 56

Accepts electrons from lipoic acid and transfers them to the electron transport chain. In PDH flavin remains bound to protein. Riboflavin is the vitamin precursor (B2) to FAD.

Front 57

Deficiency in Vitamin B2

Back 57

Fissures in the mouth, inflammation of the tongue, skin disease, severe irritation of the eyes.

Front 58

Regulated enzymes of the TCA cycle

Back 58

1. PDH complex
2. Isocitrate dehydrogenase
3. alpha-ketogluterate dehydrogenase

Front 59

Superoxide dismutase

Back 59

Takes two superoxide anion radicals and converts them to oxygen and hydrogen peroxide

Front 60

Glutathione peroxidase

Back 60

Catalyzes the reduction of hydrogen peroxide using glutathione as an electron source.

Front 61

Glutathion

Back 61

A tripeptide gamma-glutamylcysteinylglycine. Reduced form is a disulfide.

Front 62

Glutathione reductase

Back 62

GSSG is recycled back to GSH using this enzyme completing detoxyfication cycle.

Front 63

Amytal and rotenone

Back 63

Block NADH dehydrogenase and prevent the transfer of electrons from NADH-linked substrates

Front 64

Antimycin A

Back 64

Blocks the terminal step, the transfer of electrons to oxygen (respiration).

Front 65

Cyanide, carbon monoxide, and azide

Back 65

Block the terminal step, the transfer of electrons to oxygen

Front 66

Oligomycin

Back 66

Blocks synthesis of ATP by F1F0 ATPase

Front 67

Atractyloside and bongkrektate

Back 67

Inhibit the exchange of ADP and ATP between cytosol and mitochondria

Front 68

Uncouplers of oxidative phosphorylation

Back 68

Collapse the proton gradient preventing synthesis of ATP but increase respiration and electron transport.

Front 69

Mitochondrial uncoupling protein

Back 69

A protein expressed in brown fat in mammals to respond to the cold. generates heat in tissues from uncoupling the proton gradient.

Front 70

Dinitrophenol

Back 70

Small organic molecule that is membrane permeant in its pronated state collapsing the proton gradient.

Front 71

Mitochondrial myopathy

Back 71

Muscle weakness or neurological symptoms due to impaired mitochondrial function

Front 72

Mitochondrial myopathy, encephalophaty, lactic acidosis, and stroke-like episodes

Back 72

Materally inherited defects in genes encoding mitochondrial tRNAs

Front 73

Myoclonic epilepsy and ragged red fibers

Back 73

Maternally inherited defects in genes encoding mitochondrial tRNAs

Front 74

Glycogen

Back 74

Main storage source of energy in the muscle. Glycogen in muscle is used exclusively in muscle.

Front 75

The Glycolytic Pathway

Back 75

1. Once glucose is in the cell it is phosphorylated and trapped in muscle
2. After cleavage into 2 three-carbon molecules that can be interconverted by triose phosphate isomerase generates NADH.

Front 76

Pyruvate kinase

Back 76

Formation of a CH bond after donation of phosphate of PEP to ADP drives the reaction to become favorable enabling ATP formation.

Front 77

Anaerobic glycolysis

Back 77

1. Used when oxygen is limiting as in vigrorous exercise
2. Needs to recycle NADH to prevent the end of glycolysis
3. lactate dehydrogenase recycles NADH back to NAD+ to allow continued flux through glycolysis

Front 78

Cori Cycle

Back 78

Liver can recycle lactate produced by muscle back to glucose. Energy requiring pathway of gluconeogenesis.

Front 79

Glycogen synthase

Back 79

Makes glycogen in response to high energy signals.

Front 80

Glycogen phosphorylase

Back 80

Makes Glucose 1-P in response to low energy signals.

Front 81

Activation of glycogen degradation

Back 81

1. Activation of cAMP dependent protein kinase A phosphorylates phosphorylase kinase and activates it.
2. High calcium provides independent way to activate phosphorylase kinase leading to rapid activation during muscle contraction
3. Phosphorylase phosphatase is inactivated by phosphorylation leading to a large increase in degradation of glycogen

Front 82

Control of phosphofructokinase 1

Back 82

1. A major control point for glycolysis, phosphofructokinase 1 and fructose-1,6-biphosphatase are reciprically regulated
2. PFK1 activation with inhibition of FBPase increases flux through glycolysis considerably.

Front 83

Fructose-2,6-biphosphate

Back 83

1. P26P is made from F6P and provides signal that indicates availability of glucose for metabolism acting like AMP like signal.
2. In skeletal muscle, increased fructose 6 phosphate stimulates PFK2 activity and generates more F26P which stimulates PFK1 and activates glycolysis

Front 84

Phosphocreatine as energy source in contracting muscle

Back 84

Muscle stores high energy phosphates in phosphocreatine. This molecule buffers the ATP concentration against change.

Front 85

Respiration

Back 85

The flow of electrons down the electron transport chain to oxygen

Front 86

How many protons are used to make one molecule of ATP

Back 86

3 protons