What is glycolysis? What else does it generate?

Conversion of 1 glucose to 2 pyruvate - ATP directly generated - NADH generated from oxidation metabolites

What rxns are anabolic? Glycogen synthesis, Glycogenolysis, Gluconeogenesis, Glycolysis

- Glycogen synthesis - Gluconeogenesis

Does glucose have an aldehyde or ketone group?

Aldehyde

Is glycolysis anaerobic or aerobic?

Both - NADH generated w/ aerobic

How many enzyme-catalyzed rxns occur in the cytosol?

10

What are the 2 stages of glycolysis?

1. Energy investment 2. Energy payout

What happens in energy investment phase?

- Glucose needs to be activated - ATP consumed - Hexose involved

What happens in energy payout phase?

- Energy harvested in ATP - NADH generates - Triose involved

What is step 1?

Glucose -> GAP (G3P) x 2

How many ATP consumed per glucose?

2

What enzyme catalyzes the reaction: Glucose -> GAP?

Hexokinase (regulated) - Not rate limiting

Describe the factors of the rxn: glucose -> GAP

- Irreversible, exergonic, G<<0 - Coupled (ATP used) - P transfer rxn

Glucose and fructose are ________ isomers

Structural

Fructose is what type of sugar?

Ketohexose

Is glucose -> fructose reversible?

Yes, G ~ 0

Which rxn is catalyzed by PFK-1?

F6P -> F1,6BP

What are the factors of: F6P -> F1,6BP 3

- Irreversible, exergonic, G << 0 - Coupled - P transfer

Is PFK -1 regulated?

Yes - Rate limiting step

What is the lysis step in glycolysis?

F1,6BP -> DHAP + GAP (isomers)

Is the F1,6BP -> DHAP + GAP rxn irreversible?

No, its reversible G ~ 0

2 molecules of ______ are produced from 1 molecule of F1,6BP

GAP

Every rxn from GAP step to pyruvate happens ____ per glucose

Twice

What is step 2 of glycolysis?

GAP x 2 -> Pyruvate x 2

How many ATP generated per glucose? NADH per glucose?

ATP: 4/glucose NADH: 2/glucose

What is the oxidation rxn?

GAP + NAD+ + Pi -> 1,3BPG + NADH + H+

What are the factors of: GAP -> 1,3BPG 4

- Oxidation - Reversible - Energy capture step - Catalyzed by GAPDH

Why does 1,3BPG have a high energy intermediate?

Because it is an acyl P (P attached to carboxylate)

1,3BPG has a large ____________ potential

Phosphate transfer

Synthesis of __________ from 1,3BPG

ATP

What are the factors of: 1,3BPG -> Phosphoglycerate

- Reversible - Coupled - Energy capture - Substrate level phosphorylation

How many ATP per 1,3BPG?

1

What is the isomerization of energy payout step? Reversible?

3-Phosphoglycerate -> 2-Phosphoglycerate - Reversible

What is the dehydration rxn?

2-Phosphoglycerate -> PEP

What are the factors of: 2-Phosphoglycerate -> PEP

- Reversible - High energy intermediate

What is the equation for the production of pyruvate?

PEP + ADP + H+ -> Pyruvate + ATP

Why is enolpyruvate (intermediate) immediately converted to pyruvate?

Unstable

What are the factors of PEP -> Pyruvate

- G << 0 (irreversible) - Coupled - P transfer (substrate level) - Catalyzed by pyruvate kinase - Energy capture

The rate of flux is metabolic pathways is regulated by what 4 processes?

- Substrate availability - Alteration of enzyme activity - Alteration of amount of enzyme - Compartmentation

What are the regulated processes?

- Substrate availability - Enzyme regulation

G6P is an _________ of hexokinase

Negative allosteric effector (inhibitor)

PFK-1 is allosterically regulated by _____ and ____

- AMP/ADP - PEP

What doe elevated PEP levels mean?

Products of glycolysis not being consumed

Conc of ADP/AMP is a good indicator of what?

Need for ATP

What is pyruvate kinase inhibited by? activated by?

Inhibited by ATP Activated by F1,6BP

What kind of activation does F1,6BP do for pyruvate kinase?

Feed forward

Both ________ and ____ are inhibited by ATP

PFK-1 and PK

Glycogen is synthesized from ________

G6P - Anabolic

What does the breakdown of glycogen use? What bonds are broken?

Inorganic P to break glycosidic bonds

T/F: ATP is used to generate G6P from glycogen

False, ATP is not used

What are the fates of pyruvate? 3

- Yeast (reductive) - Rapidly contracting muscle (reductive) - Oxidative phosphorylation

Why is an anerobic fate for pyruvate required?

- Regenerate NAD+ for oxidation rxn in glycolysis

Glycolysis produces.... 3

- 2 pyruvate - 2 NADH - net 2 ATP - Oxidative phosphorylation - Pyruvate reduction

NADH needs to be _________ for glycolysis to continue

Reoxidized to NAD+

What does pyruvate reduction produce?

- Ethanol - Lactate

T/F: Lactate is an acid

False - Lactic acid is protonated form

How is lactate exported?

Exported from muscle via membrane transporter protein

How can acidotic damage to muscle fibers occur?

Hydrolysis of ATP by myosin during vigorous muscle contraction

Lactate is a _______ for cardiac tissue

Metabolic fuel - Always aerobic and oxidative

What is an anaerobic fate pf pyruvate?

Ethanol - yeast

What occurs in the yeast rxn?

- Decarboxylation - Reduction - Final products: CO2, Ethanol, NAD+

What is pyruvate dehydrogenase rxn catalyzed by?

Pyruvate dehydrogenase complex - Quaternary structure

What does the pyruvate dehydrogenase rxn do? Where does it occur?

Link glycolysis to citric acid cycle - Inside mitochondria, in the matrix

What rxns happen in the matrix? 4

- Pyruvate dehydrogenase - Citric acid cycle - Oxidative phosphorylation - Beta oxidation

Pyruvate is converted to _______ in mitochondrial matrix, How?

Acetyl-coA - PDC

What transporter protein is required for crossing mito membrane?

Pyruvate translocase

What is transported w/ pyruvate across mito membrane?

A proton

What is the functional portion of acetyl coA?

- Thiol (reactive sulfhydryl group) - Forms thioester bond w/ acetyl

Is the formation of acetylcoA irreversible or reversible step?

Irreversible

What is the pyruvate dehydrogenase rxn?

Pyruvate + coA + NAD+ -> Acetyl coA + NADH + CO2

What are the cofactors that PDC?

NAD+, FAD, CoA - Kinases and phosphatases

Is PDC regulated?

Yes

T/F: Acetyl CoA cannot be used to make glucose

True

What is PDC regulated?

- NAD+/NADH - Acetyl CoA - Ca+

What is NADH effect on PDH?

NADH inhibits (regulates) PDH

What activated PDH?

Activation (phosphorylation of PDH)

What is Acetyl coA effect on PDH?

Inhibitor

What is Ca effect on PDH?

Activator

What is the protein phosphatase activation?

Dephosphorylation of PDH

PDH is regulated by reversible _________

Phosphorylation

Reversible phosphorylation is switched off when energy levels are _________

High

Reversible phosphorylation switches off the activity of the complex via a _______

Kinase

Reversible phosphorylation activates the complex via _____________

Phosphatase

Inhibition of the complex is caused by what?

NADH and Acetyl CoA

Activation of the complex is caused by what?

NAD+ and HS-CoA