Biochem Lec 21- Metabolism: Coenzymes and Energetics

What does the process of metabolism allow a cell to do?

1. Extract energy from its environment

2. Synthesize the chemical building blocks of macromolecules

Briefly describe metabolic pathways.

• Metabolic pathways are coupled and interconnected

• They contain many recurring elements including intermediates and modes of regulation

• Metabolic pathways are basically sequences of chemical reactions that convert a particular molecule into another in a carefully defined way

Define catabolism.

Catabolism→ reactions that break down complex molecules into simpler ones to capture energy in useful forms

• Oxidation of carbon-rich “fuel” molecules powers the formation of ATP (e.g., glucose and fatty acids)

Define anabolism.

Anabolism→ reactions that construct a more complex molecule from simpler molecules by using energy

What are forms of “useful” energy?

1. Chemical

• ATP and other high energy phosphates

• Thioesters (Co-enzyme A)

2. Ionic

• Proton and ion gradients

4. Reducing power

• Nicotinamide (niacinamide) and Flavin co-enzymes

Chemical energy “currency” in the cell is phosphate based. Explain how ATP fits into this.

• ATP acts as the free-energy donor in most energy-requiring processes

• ATP→ a nucleotide consisting of adenine, ribose, and a triphosphate unit

• ATP acts as an energy carrier because the hydrolysis of its phosphoanhydride bonds is very exergonic→ -30.5 kJ/mol

• ATP is a “phosphoryl group donor”→ has high “phosphoryl transfer potential

Why is the hydrolysis of ATP’s phosphoanhydride bonds very exergonic. Why is this?

• P_i has greater resonance stabilization than ATP phosphoryl groups

• Electrostatic repulsion of the triphosphate makes ATP less stable→ donation of phosphoryl group makes products more stable than reactants

• Entropy increases when P_i is liberated

• ADP and P_i can form new interactions with water

What do reactions using energy coupling often involve and why?

They often involve the hydrolysis of ATP→ ATP has a very negative free energy that can lower the overall free energy of a typically unfavorable reaction when they are energetically coupled

What determines whether a reaction will occur spontaneously? How does energetic coupling fit into this?

1. The standard biological free energy (ΔG^º”)

2. The relative concentrations of substrates [A] and products [C] and [D]

The overall ΔG for a chemically coupled series of reactions equals the sum of the ΔG of the individual steps:

A→ B + C ΔG^º’= 21 kJ/mol

B→ D ΔG^º’= -34 kJ/mol

Overall ΔG^º’= (21 + -34)= -13 kJ/mol

What are 3 enzymes that use ATP to drive unfavorable reactions?

1. Kinases→ phosphotransfer

• ROH + ATP→ RO-(PO₃^-) + ADP

2. Carboxylases→ addition of CO₂

• R-CH₃ + CO₂ + ATP→ RCH₂-COO^- + ADP + P_i

3. Synthetases→ ligation of two substrates

• A + B + ATP→ A-B + ADP + P_i

Describe the ATP cycle.

ATP→ ADP

• Motion

• Active transport

• Biosyntheses

• Signal amplification

ADP→ ATP

• Oxidation of fuel molecules

• Photosynthesis

What is the energy status of any given cell manifested by?

Adenylate Energy Charge

AEC fluctuates from 1 (all ATP) to 0 (all AMP… death)

What is Co-Enzyme A?

Co-Enzyme A is a chemical form of useful energy:

• Derived from the dietary vitamin pantothenic acid

• Stores energy in the form of an activated thioester bond

• Contains a thiol group that carries activated acyl groups in a thioester linkage

• “Activated carrier”→ the thioester is a high energy bond that can be used for biosynthesis or for the production of energy

• Vitamin→ Pantothenic acid

• Coenzyme→ Coenzyme A

• Typical reaction type→ Acyl group transfer

• Consequences of deficiency→ Hypertension

What are NADH/NADPH? Describe their structure and what they do.

NADH and NADPH are “reducing power” forms of useful energy:

• Activated carrier

• R= H→ nicotinamide adenine dinucleotide (NAD⁺)→ catabolism and energy production

• R= phosphate→ nicotinamide adenine dinucleotide phosphate (NADP⁺)→ reducing power for biosynthesis

• Contains an adenine nucleotide involved in binding to enzyme active site and a nicotinamide ring that carries hydrogens and electrons (reducting power)

• Serve as two electron acceptors in oxidation-reduction reactions

• Enzymes that catalyze these reactions and that use NAD⁺ or NADP⁺ as a coenzyme are called “dehydrogenases” or “oxidoreductases”

• Vitamin→ Nicotinic acid

• Coenzyme→ Nicotinamide adenine dinucleotide (NAD⁺)

• Typical reaction type→ Oxidation-reduction

• Consequences of deficiency→ Pellagra (dermatitis, depression, diarrhea)

What is FADH₂?

FADH₂ is a “reducing power” form of useful energy:

• Activated carrier

• Serves as a two electron acceptor for dehydrogenases and oxidoreductases

• It generally has less reductive power than NAD⁺

• FAD (flavin adenine dinucleotide) is tightly (often covalently) bound to enzymes (“flavoproteins'“)

• Vitamin→ Riboflavin (B₂)

• Coenzyme→ Flavin adenine dinucleotide (FAD)

• Typical reaction type→ Oxidation-reduction

• Consequences of deficiency→ Cheilosis and angular stomatitis (lesions of the mouth), dermatitis

Summarize activated carriers.

• Carbon fuel oxidation is performed in metabolism through the help of “activated carriers”

• ATP is an activated carrier of phosphoryl groups because phosphoryl transfer from ATP is an exergonic process

• Metabolism also uses other activated carriers for fuel oxidation, which are derived from vitamins (coenzymes)→ REDUCING POWER