01: Cellular Metabolism and Regulation

________ is a collection of reactions responsible for

• the generation of energy for the cells

• the use of this energy, along with simple organic precursor molecules, to make more complicated molecules for the cell

Primary metabolism

_________: subset of those reactions that lead to the synthesis of complex molecules from simple precursors

Anabolism

________: subset of those reactions that lead to the breakdown of energy-yielding molecules

Catabolism

pathway: The set of linked reactions from precursor to final product, along with enzymes, cofactors, and regulatory factors

• Enzyme + cofactor = _____

Holoenzyme

Pathways can be

linear, branched, circular

_____: When a portion of the output of a system (or a process) returns as input for that system (or process), it is called feedback

Feedback

Negative feedback

• Product of the pathway binds to the enzyme and changes enzyme conformation

  • ______

  • Reaction “stops” as a result

Competitive, Non-competitive/Allosteric inhibition

Metabolic control mechanisms

Concentration, Compartmentalization, Enzyme activation and deactivation, Reciprocal regulation of competing pathways

Concentration mechanisms include the following factors:

Enzyme levels, Substrates, Cofactors

Different or opposing pathways are placed in different cellular compartments i.e. cell organelles, or different organs (muscle v. liver)

• Nucleus: DNA replication, synthesis of mRNA

• Mitochondria: Krebs’ cycle, fatty acid oxidation

• Cytosol: glycolysis, fatty acid synthesis

The transport systems that ferries material across the membranes are also regulated

• Affects concentration of enzymes, substrates and cofactors on either side of the membrane

• E.g. OATP (Anion Transporter Proteins), P-glycoprotein

Compartmentalization

Enzymes with mutually opposing roles may co-exist in the same organelles

• Their activity is controlled by the process of ________

  • Depending upon the immediate physiological state, one set of enzymes have to be shut off when the other set of enzymes is active

• E.g. phosphatases and kinases in the cytosol

  • These enzymes have opposite types of actions. Kinases load phosphate groups on molecules, while phosphatases help unload those phosphate groups.

reciprocal regulation

Phosphorylation is catalyzed by protein _____.

kinases

Dephosphorylation is catalyzed by protein _____

• or they can be spontaneous.

phosphatases

Typically, proteins are phosphorylated on the hydroxyl groups of _____

Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y)

Stages of digestion of food:

• Polymeric foodstuff is broken down to monomeric components

• Enzymes in the mouth and gut; acid in the stomach; bile salts in the intestine

Stage 1

Stages of digestion of food:

• Monomeric components are converted to simple metabolic intermediates

• Components are transported to the cell by the blood; conversion occurs within the cell

Stage 2

Stages of digestion of food

• Degradation of simple intermediates to CO2, NH3, water and urea

  • Catalyzed by enzymes

  • Energy-generation via metabolic pathways

Stage III

coenzymes: cosubstrates

ATP, NAD/NADP, Coenzyme A, Tetrahydrofolate

coenzymes: prosthetic group

FMN/FAD, Biotin, Retinal, Vitamin K

transfers activated acyl groups

Coenzyme A (CoA, CoASH)

Nicotinamide Adenine Dinucleotide (NAD+ and NADH)

Flavin Adenine Dinucleotide (FAD and FADH2)

Redox Cofactors

NAD and NADP Are Common Redox Cofactors

• These are commonly called ________

• They can dissociate from the enzyme after the reaction.

• In a typical biological oxidation reaction, hydride from an alcohol is transferred to NAD+, giving NADH

pyridine nucleotides

Flavin Cofactors Allow Single Electron Transfers

• Permits the use of molecular oxygen as an ultimate electron acceptor

• _______

• Flavin cofactors are tightly bound to proteins.

flavin-dependent oxidases

Nicotinamide

• Co-substrate derived from ______

  • NADH (Nicotinamide Adenine Dinucleotide)

  • NADPH (Nicotinamide Adenine Dinucleotide Phosphate)

niacin (Vitamin B3)

Flavins

• Derived from _______

  • FAD (Flavin Adenine Dinucleotide)

    • FADH2 is the reduced form

  • FMN (Flavin Mono Nucleotide)

    • FMNH2 is the reduced form

• Flavins participate in redox reactions

  • 1 e- or 2 e-

  • Conjugated central ring serves as an electron sink

riboflavin (Vitamin B2)

Vitamins

• _______ (Vitamin B1; cofactor for E1 of PDH Complex: seen in TCA Stage I)

Thiamine

Vitamins

• ______ (Vitamin B2; part of Flavins)

Riboflavin

Vitamins

• _______ (Vitamin B3; part of Nicotinamides)

Niacin

Vitamins

• _______ (Vitamin B5; part of CoA-SH)

Pantothenic acid

Vitamins

• _______ (Vitamin B6; part of pyridoxal phosphate; seen in AA metabolism)

Pyridoxine

Vitamins

• ________ (Vitamin B7; prosthetic group associated with pyruvate carboxylase: seen in Gluconeogenesis)

Biotin