ATP=cellular energy
Cells extract energy from their environment and use the energy for a host of biological activities including biosynthesis. The reactions of energy extraction and energy use are called metabolism or intermediary metabolism. Basic principles govern energy manipulations in all cells: 1. Molecules are degraded or synthesized stepwise in a series of reactions termed metabolic pathways. 2. ATP is the energy currency of life. 3. ATP can be formed by the oxidation of carbon fuels. 4. Although many reactions occur inside a cell, there are a limited number of reaction types involving particular intermediates that are common to all metabolic pathways. 5. Metabolic pathways are highly regulated.
Phototrophs are photosynthetic organisms that obtain energy by trapping sunlight Chemotrophs obtain energy by oxidation of foodstuffs Metabolic pathways: Some convert fuels to energy and other useful forms others require energy to proceed 1) Catabolic reactions: 2) Fuels to CO2 + H20 + energy 3) Anabolic reactions: 4) Synthesis of fats, glucose and DNA require energy
Metabolic pathways can be divided into two types: 1. Catabolic pathways combust carbon fuels to synthesize ATP. 2. Anabolic pathways use ATP and reducing power to synthesize large biomolecules. Some pathways, called amphibolic pathways, can function anabolically or catabolically. Although anabolic and catabolic pathways may have reactions in common, the regulated, irreversible reactions are always distinct.
In order to construct a metabolic pathway, two criteria must be met: 1. The individual reactions must be specific. 2. The pathway in total must be thermodynamically favorable. A thermodynamically unfavorable reaction in a pathway can be made to occur by coupling it to a more favorable reaction.
Phosphoryl-transfer potential the standard free energy of hydrolysis is a means of comparing the tendency of organic molecules to transfer a phosphoryl group to an acceptor molecule. ATP has a higher phosphoryltransfer potential than glycerol 3-phosphate.
Resonance stabilization of orthophosphate ATP has a small number of such structures whereas ADP and orthophosphate have many
Other compounds with high phosphoryl-transfer potential:
ATP has a phosphoryl-transfer potential intermediate between high phosphorylpotential compounds derived from fuel molecules and acceptor molecules that require the addition of a phosphoryl group for cellular needs. Creatine phosphate serves as an energy reserve in vertebrate muscle.
ATP is intermediate energy allows it to function efficently as a carrier of phosphoryl groups
Why Phosphates? 1 Phosphate esters are thermodynamically unstable but kinetically stable 2 Negative charges of phosphate esters are resistant to hydrolysis in the absence of enzymes 3 PO4 can only be added or removed from a molecule by enzymes 4 PO4 forms the backbone of DNA
ATP-ADP Cycle
The ultimate electron acceptor in the oxidation of C is O2 the more reduced a carbon is to begin with the more free energy released by its oxidation:
Fats are more efficient fuel source than carbohydrates because the carbon in fats is more reduced
G3P is a metabolite of glucose: oxidation of this aldehyde to the acid releases energy
The formation of ATP from G3P occurs in two steps the first oxidation step requires NAD+ and HPO4 resulting in a phosphorylated intermediate 1,3-BPG:
The second step ADP is phosphorylated to ATP with the 1,3-BGP phosphate group:
Proton Gradients across membranes are created by the oxidation of carbon fuels pumping protons out resulting in the influx of protons and the synthesis of ATP from ADP
The generation of energy from food occurs in three stages: 1. Large molecules in food are broken down into smaller molecules in the process of digestion. 2. The many small molecules are processed into key molecules of metabolism, most notably acetyl CoA. 3. ATP is produced from the complete oxidation of the acetyl component of acetyl CoA.
The digestion of food results in the generation of a few simple units that play a key role in metabolism
ATP is an activated carrier of phosphoryl groups. Other activated carriers are common in biochemistry, and they often are derived from vitamins.
NADH/NAD + and FADH2/FAD are activated carriers of electrons for fuel oxidation. NADH/NAD + participate in reactions such as the following: FADH2/FAD participate in reactions such as the following:
NAD is a major electron carrier in the oxidation of fuels NAD+ Nicotinamide adenine dinucleotide R=H NADP Nicotinamide adenine dinucleotide phosphate R=P
In the oxidation of a substrate, the nicotinamide ring of NAD+ accepts a hydrogen ion and two electrons the reduced form is NADH
The other electron carrier is the coenzyme flavin adenine dinucleotide FAD and FADH2
FAD consists of a flavin mononucleotide (blue) and an AMP unit (black)
The electrons and protons are carried by the isoalloxazine ring component of FAD
Reductive biosynthesis uses NADPH as the electron donor not NADH which is used for ATP generation The Phosphate group on NADP allows enzymes to to distinguish the molecules for their proper function
NADPH/NADP + is the electron carrier for reductive biosynthesis. Two molecules of NADPH are required for the reduction of a keto group to a methylene group in fatty acid synthesis.
Coenzyme A (CoA or CoASH) is an activated carrier of acyl groups such as the acetyl group.
The transfer of the acyl group is exergonic because the thioester is unstable.
Coenzyme A is a carrier of acetyl groups through a thioester bond
NADH, NADPH and FADH2 react slowly with O2 Likewise ATP and acetyl CoA are hydrolyzed slowly without a catalyst The stability of these molecules allow them to control the flow of free energy and reducing power The existence of a recurring set of activated carriers in all organisms is a unifying theme in biochemistry
Many activated carriers are derived from vitamins Vitamins are organic molecules that are needed in small amounts in the diets of higher animals as higher animals have lost the capacity to synthesize these molecules during the course of evolution E. Coli can thrive on glucose and organic salts, humans require at least 12 vitamins in their diet. The biosysnthesis of vitamins is often complex requiring many steps it is easier to acquire these nutrients in the diet than to synthesize them de novo
The B vitamins function as coenzymes. Vitamins A, C, D, E, and K play a variety of roles, but do not serve a coenzymes.
Water-soluble vitamins
Not all vitamins function as coenzymes those with letter designation have a diverse array of functions
Fat-soluble vitamins
There are thousands of metabolic reactions, but they can be subdivided into six types
Oxidation-reduction reactions
Ligation reactions
Isomerization reactions
Group-transfer reactions
Hydrolytic reactions Cleave bonds by the addition of H2O
Functional groups may be added to double bonds to form single bonds or removed from single bonds to form double bonds The enzymes that perform this step are called lyases
A dehydration reaction: critical step in glycolysis
Metabolic pathways must be regulated to create homeostasis or a stable biochemical environment. To maintain homeostasis, the levels of available nutrients must be constantly monitored and metabolism adjusted to meet the biochemical needs of the cell. Homeostasis is maintained by three crucial regulatory strategies.
Metabolism is controlled by: 1)The amount of enzymes 2)Their catalytic activities 3)The accessibility of substrates
The fact that ATP, NADH, FADH2 and coenzyme A all contain adenosine diphosphate units may be a reflection of the role of RNA in early metabolism. In the postulated RNA world, RNA served both as a catalyst and an information storage molecule.
ADP is an ancient module in metabolism