Traits of Metabolism (6)

Glycolysis 

 "Breakdown of Glucose"

Glucose -----> 2 Pyruvate + 2 ATP + 2NADH

10 Steps, 10 enzymes

**EXERGONIC because ΔG is negative...E released

Glycolysis Step 1

Glucose + HEXOKINASE -----> Glucose 6-phosphate

G + HK ----> G6P

**1 ATP hydrolyzed into ADP

**Glucokinase is used in the liver

**1st point of regulation in this pathway

Glycolysis Step 2 

G6P + G6P ISOMERASE ----> Fructose 6-Phosphate

Glycolysis Step 3 

 F6P +Phosphofructokinase-1 ----> Fructose 1,6-biP

F6P + PFK-1 ----> FBP

** 1 ATP hydrolyzed into ADP

** The MOST regulatory step in this path 

Glycolysis Step 4 

FBP + ALDOLASE ----> Dihydroxyacetone phosphate

AND Glyceraldehyde 3-phosphate

FBP + aldolase ----> DHAP + G3P

Glycolysis Step 5 

DHAP + TRIOSE PHOSPHATE ISOMERASE ----> G3P

**This is an isomerization 

Glycolysis Step 6 

G3P + G3P DEHYDROGENASE ---->

1,3-Bisphosphoglycerate

G3P + G3PD ----> 1,3BPG

** 1 NAD ----> 1 NADH

Glycolysis Step 7 

1,3BPG + PHOSPHOGLYCERATE KINASE ----> 3-phosphoglycerate

1,3BPG + PGK ----> 3-PG

** 1 ADP phosphorylated to yield 1 ATP 

Glycolysis Step 8

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

Glycolysis Step 9

2-PG + ENOLASE ----> phosphoenolpyruvate

** 1 H2O produced (dehydration rxn)

** This step also requires MG2+ 

Glycolysis Step 10 

PEP + PYRUVATE KINASE ----> pyruvate

PEP + PK ----> pyruvate

** 1 ADP phsophorylated to ATP

**Mg2+ required

**3rd main control point in pathway

Control Points of Glycolysis 

Steps 1, 3, and 10

1: hexokinase

3: phosphofructokinase - MAIN ONE

10: pyruvate kinase 

Fates of Pyruvate (4) 

1. Conversion to Lactate

2. Complete oxidation by CAC & oxidative phosphorylation

3.  Conversion to ethanol (facultative anaerobes only...ie: yeast)

4.  page 19 of notes...don't know what it is 

Pentose Phosphate Pathway 

produces C3, C4, C5, C6, & C7 sugars

does not require O2 and occurs in cytoplasm

G6P + 2NADP ----> ribulose 5-P

ribulose 5-P isomerization ----> ribose 5-P

 1 G6P yields 1 ribose, 2 NADPH, and 1 CO2

2nd phase of pathway yields all the sugars 

Gluconeogenesis 

Synthesis of glucose from non-carb precursors

Glycolysis cannot simply act in reverse due to the 3 irreversible steps

Only occurs in liver and kidneys b/c they possess enzymes necessary to overcome 3 irreversible glycolytic steps

Reversal of Glycolysis Step 10 in Gluconeogenesis 

AKA: Gluconeogenesis Step 1 

pyruvate + PYRUV. CARBOXYLASE ----> oxaloacetate

** requires CO2 and ATP

Oxaloacetate + PEP CARBOXYKINASE ----> PEP

        (PEPCK) 

**Occurs in mitochondria, which must be in high E state

Reversal of Glycolysis Step 3 in Gluconeogenesis 

FBP + FRUC. BISPHOS. PHOSPHATASE ----> F6P

** requires ATP

**hydrolysis rxn 

Reversal of Glycolysis Step 1 in Gluconeogenesis 

G6P + G6phosphatase ----> GLUCOSE!!!!

** that enzyme is from the liver 

Glycogen

 a polymer of glucose, which is an E store in the liver and muscles that can be rapidly broken down to G6P for glycolysis

composed of α(1→4) linkages in chain and α(1→6) in branches

Glycogenesis Step 1

G6P + PHOSPHOGLUCOMUTASE ----> G1P

G6P + PGM ----> G1P 

Glycogenesis Step 2 

Activation of G1P by hydrolysis of UTP

G1P + UDP-GLUCOSE PYROPHOSPHORYLASE ---->

UDP-glucose

** 1 UTP used 

Gylcogenesis Step 3 

addition of glucose unit to glucose polymer (glycogen)

(glucose)_n + UDP-G + GLYCOGEN SYNTHASE ----> (glucose)_n+1 + UDP

 
= GLYCOGEN

Glycogenolysis 

degradation of glycogen

(glucose)_n + GLYCOGEN PHOSPHORYLASE ----> (glucose)_n-1 + G1P

G1P + PHOSPHOGLUCOMUTASE ----> G6P

G6P then enters glycolysis (skeletal muscle and liver) or is converted to glucose (liver)

Cleaving α(1→6) linkages in glycogen

GLYGOGEN PHOSPHORYLASE cannot, so α(1→6)-GLUCOSIDASE turns them into α(1→4) linkages so GP can access them

**GP does not act on 1-4 links than have 1-6 branching 

Control of Glycogenesis and Glycogenolysis 

1. glycogen phosphorylase 

2. glycogen synthase

high G6P inhibits glycogenolysis, and activates synthesis...and vice versa

3. epinephrine: stimulates degradation in muscle and liver

4. glucagon (liver): sitmulates gluconeogenesis (forms glucose from pyruvate) & glycogenolysis (forms glucose from glycogen)

Acetyl Coenzyme A

Coenzyme A:

1. ADP + 3' phosphate

2. pantothenic acid

3. β-mercaptoethylamine

Acyl group:

1. Acetyl attached to thiol of β-mercaptoethylamine

SH emphasized by incorporating it into nomenclature 

Pyruvate dehydrogenase complex (definition and rxn)

Converts pyruvate into acetyl-CoA in the mitochondrial matrix

pyruvate + CoA + NAD⁺ + PDH ---->

acetyl-CoA + CO₂ + NADH

 3 Acetyl-CoA formation sources

Thioester 

compounds resulting from bonding of Sulfur with an acyl group

ex: Acetyl-CoA 

PDH kinase 

attaches phosphate to PDH to inhibit it

PDH kinase is inhibited by pyruvate and low E indicators such as NAD, ADP, CoA

activated by high E indicators such as ATP, NADH, acetyl-CoA 

PDH phosphatase 

activates PDH by removing phosphate 

PDH phosphatase activated by Mg2+ and Ca2+ 

Pyruvate dehydrogenase complex 

1. PDH (E1) decarboxylates pyruvate and binds the extracted hydroxyethyl group to TPP

2.  Hydroxyethyl oxidizes to acetyl group during lipoic acid transfer (which is covalently bound to E2: lipoyl transacetylase)...E2 also transfers acetyl to CoA

3.  Reduced lipoic acid reduces FAD of E3 (dihydropoyl dehydrogenase) to FADH₂, which is then reoxidized to FAD by conversion of NAD⁺ to NADH.

Citric Acid Cycle 

8 step reaction in which 2 C's of acetyl-CoA are oxidized to CO2

main path for release of E from acetyl-CoA

Exergonic process overall, steps 2 and 8 endergonic

Step 1 of CAC 

condensation (requires water)

acetyl-CoA + oxaloacetate + CITRATE SYNTHASE -->

citrate and CoA 

**citrate inhibits glycolysis by inhibiting PFK-1 

Step 2 of CAC 

dehydration followed by hydration...

citrate - H2O ----> cisAconitate (int)

 cisAconitate + H2O ----> Isocitrate

Both use enzyme ACONITASE 

Step 3 of CAC 

oxidative decarboxylation

isocitrate + ISOCITRATE DEHYDROGENASE ---->

2-oxoglutarate 

Step 4 of CAC 

2-oxoglutarate + CoA + 2-ODH complex ---->

succinyl-CoA 

Step 5 of CAC 

succinyl-CoA + S-CoA SYNTHETASE ---->

succinate

**converts GDP and phosphate to GTP, CoA is byproduct as well 

Step 6 of CAC 

** oxidation rxn

succinate + SUCCINATE DH ----> fumarate

** only step involving FAD, 2 H's eliminated from succinate and applied to FAD to produce FADH₂

**SDH is only membrane bound enzyme in CAC 

Step 7 of CAC 

Fumarate + FUMARATE HYDRATASE ----> L-Malate

**enzyme aka FUMARASE

** H2O added 

Step 8 of CAC 

Malate + MDH ----> Oxaloacetate

** NADH produced from NAD+

**OA regenerated and can now condense with another acetyl-CoA 

Role of CAC in Cellular Respiration 

Does not involve O2, but rather the production of CO2, which affects the stoichiometry of the respiration reaction 

Control Points of CAC 

Steps 1, 3, 4, and 6

1: citrate synthase

3: isocitrate dehydrogenase

4: 2-oxoglutarate dehydrogenase

6: succinate dehydrogenase 

Glyoxylate Cycle 

modified CAC in some plants and bacteria that can use acetate as C source for carbohydrate synthesis

unique rxns:

isocitrate + ISOCITRATE LYASE ---->

glyoxylate + succinate

glyoxylate + acetyl-CoA + MALATE SYNTHASE --->

Malate + CoA

overall rxn:

2 acetyl-CoA + 2H2O +NAD⁺ ----> succinate^2- + NADH + 2CoA

Electron transport chain 

 forms the means by which electrons are channeled to O2 and protons to produce H2O

components:

NAD⁺/NADH, flavin nucleotides,CoQ, cytochromes, iron-sulfur proteins

receives high E e^- from NADH and FADH2 and uses that E to pump PROTONS out of matrix

complexes I III and IV transport protons from matrix to IMS

oxidative phosphorylation 

the creation of ATP via chemiosmosis as a result of electron transport

free energy from electron transport chain utilized by proton-translocating ATP-synthase

requires about 3 protons to produce 1 ATP 

oligomycin 

inhibits ATP synthesis by binding and interfering with H+ transport

NAD⁺ stands for...

nicotinamide adenine dinucleotide 

reduction of NAD⁺

NAD⁺+ H⁺ + 2e^- ----> NADH

β-oxidation

acyl-CoA broken down to generate acetyl-CoA in mitochondia and peroxisomes

occurs through the sequential removal of 2 carbons by oxidation at the b-carbon position of the acyl-CoA 

ketone bodies 

body forms these when there is not enough insulin, and thus fat is used for energy instead of glucose

they are toxic, acidic chemicals 

prevalent in insulin-dependent diabetics since they are deficient in insulin to use glucose, therefore fatty acids are used and ketone bodies are produced 

fatty acid oxidation 

yields much more ATP per carbon atom

F.A. stored in the form of triacylglycerols

oxidation occurs in mitochondria