• Energy-yielding nutrients. Protein, carbohydrate and lipid

• Micronutrients. Vitamins and minerals necessary for biochemical processes

• Essential fiber. Non-digestible polysaccharide material, essential for normal functioning of animal digestive systems (i.e. colon)

Animals are unable to synthesize certain amino acids (humans can only make 10 of the 20 common amino acids). The amino acids that an animal is unable to synthesize must be obtained from the diet (i.e. by consuming plants or microorganisms), and these amino acids are termed "essential amino acids".

• Glucogenic amino acids: can be converted into glucose

• Ketogenic amino acids: can be converted into fatty acids or keto acids

• If plenty of fats and carbohydrates are available, then the glucogenic and ketogenic amino acids from excess dietary protein are not immediately needed for energy production and are converted to triacylglycerol and stored as fat

Protein is an important source of nitrogen in the diet. Protein within the body is constantly turning over (i.e. being degraded and resynthesized). Furthermore, there is a general demand for protein synthesis when an organism is growing. The Nitrogen Balance refers to the relationship between the supply and demand for nitrogen (i.e. protein) within an organism.

Carbohydrates are also an essential structural component of nucleic acids, nucleotides, glycoproteins and glycolipids. However, the principle role of carbohydrate in the diet is production of metabolic energy.

• Simple sugars are metabolized in the glycolytic pathway to release energy

• Complex carbohydrates (except dietary fiber) are degraded into simple sugars, which then enter the glycolytic pathway

• Metabolism can make use of a wide variety of sugars for energy production. However, the brain relies solely on glucose for an energy source

• When dietary carbohydrate exceeds the supply needed for energy requirements, it is converted to glycogen and triacylglycerols for storage

• When dietary carbohydrate is in short supply, ketone bodies are formed from acetate units to provide fuel for the brain

• Excess dietary fat is stored as triacylglycerols in adipose tissue

• A deficiency of dietary fat is problematic because some fatty acids cannot be synthesized by the human body, and must be obtained through diet. These are termed essential fatty acids

• The human body cannot synthesize linoleic, linolenic or arachidonic fatty acids. These are key components of biological membranes, and arachidonic acid is a precursor of prostaglandins (an important class of hormones). These are therefore considered essential fatty acids

"Dietary fiber" refers to molecules that cannot be broken down by enzymes in the human body.

Vitamins are essential nutrients that are required in the diet because they cannot be synthesized by human metabolic enzymes. Often, only trace levels are required, but a shortage can result in disease or death.

• A common categorization of human vitamins is whether they are water soluble or fat soluble compounds.

• Coenzymes may act as carriers of specific functional groups (e.g. methyl or acyl groups)

• They can provide chemically reactive groups that the common 20 amino acid side chains cannot provide

• Coenzymes are usually modified in the course of a reaction, and subsequently chemically regenerated back to their useful active form. Thus, this recycling of coenzymes means that only small concentrations are required.

• All the water soluble vitamins (with the exception of vitamin C) are coenzymes or precursors of coenzymes.

Thiamine is the precursor of thiamine pyrophosphate (TPP):

• TPP is a coenzyme

• It is a coenzyme for certain enzymes involved in carbohydrate metabolism

• It catalyzes the synthesis or cleavage of bonds to carbonyl carbons

Nicotinamide is an essential part of two important coenzymes: nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+).

• The reduced forms of these coenzymes are NADH and NADPH

• The coenzymes participate in redox reactions via the direct transfer of hydride (H^-) ions either to or from the cofactor and a substrate. The hydride transfer carries two electrons along with it (a proton transfer in acid/base catalysis carries no electrons)

• The hydride transfer involves the C4 carbon of the nicotinamide ring. The quaternary amine of the nicotinamide ring acts as an electron sink to promote acceptance of a hydride ion.

• Enzymes that are involved in such redox reactions are called dehydrogenases

• The nucleotide part of the molecule does not enter into any chemistry, but is important for recognition and binding to enzymes that will use FMN or FAD as a cofactor.

Riboflavin is a constituent of riboflavin 5'-phosphate (flavin mononucleotide, or FMN) and flavin adenine dinucleotide (FAD). The nucleotide part of the molecule does not enter into any chemistry, but is important for recognition and binding to enzymes that will use FMN or FAD as a cofactor.

The isoalloxazine ring is the core structure of the different flavin molecules. It is yellow in color and the word "flavin" is derived from the latin word for yellow, flavus.

• Flavin coenzymes can exists in three different redox states, and each state has a different color (the reduced form is colorless)

• Flavin molecules can participate in both one- and two- electron transfer reactions

• The nitrogens in the aromatic rings are more electronegative than the carbons and attract electrons (function as electron acceptors). The double bonds in the aromatic rings provide a means to accommodate more electrons - with the ability to form single bonds.

Pantothenic acid is a component of coenzyme A (CoA). The two main functions of CoA are:

1. Activation of acyl groups (R-COX) for transfer to nucleophilic acceptors

2. Activation of the a-hydrogen of the acyl group for removal as a proton

• The 4-phosphopantetheine part of CoA is also used in the same way in acyl carrier proteins (ACP's) involved in fatty acid biosynthesis

The biologically active form of vitamin B6 is pyridoxal-5-phosphate (PLP), however, the nutritional requirements can be met by either pyridoxine, pyridoxal or pyridoxol.

• Transamination

• a- and b-decarboxylation

• b- and g- elimination (not to be confused with painful elimination)

• Racemization

• Aldol reactions

These involve bonds to the amino acid Ca as well as side chain carbons. The wide variety of reactions is due to the ability of PLP to form stable Schiff base adducts with a-amino groups of amino acids:

• In PLP-dependent enzymes, the PLP is present in a Schiff base linkage with the e-amino group of an acitve site lysine

• Rearrangement to a Schiff base with the arriving amino acid substrate is a transaldiminization reaction

Vitamin B12 is not made by any animal or plant, it is produced by only a few species of bacteria. Once in the food chain, vitamin B12 is obtained by animals by eating other animals, but plants are sadly deficient. Therefore, herbivorous animals (and vegetarians) can suffer a deficiency. The structure contains a cobalt ion, coordinated within a corrin ring structure:

Vitamin B12 (cyanocobalamin) is converted in the body into two coenzymes:

Biotin acts as a mobile carboxyl group carrier in a variety of enzymatic carboxylation reactions.

• Synthesized by intestinal bacteria (finally, they do something for you)

• Biotin is bound covalently to the enzyme as a prosthetic group via an e-amino group of a lysine residue in the enzyme

• This biotin-lysine conjugated amino acid is termed a "biocytin" residue

• The lysine side-chain acts as a flexible "tether" for the biotin, and this flexibility allows the transfer of carboxylate groups within the enzyme

• It is the carrier for the most oxidized form of carbon - CO₂ (using bicarbonate as the carboxylating agent). The carbon dioxide binds as a carboxy group to one of the ring nitrogens in the biotin

Lipoic acid contains two sulfur atoms that can exist as a disulfide bonded pair, or as two free sulfhydrils. Conversion between the two forms involves a redox reaction (the two free sulfhydrils represent the reduced form). Lipoic acid is typically found covalently attached to a lysine side chain in enzymes that use it as a cofactor, as a lipoamide complex.

• Lipoic acid is an acyl group carrier (R-CO-X)

• It also functions to transfer electrons during oxidation and decarboxylation of a-keto acids

• Pyruvate dehydrogenase and a-ketoglutarate dehydrogenase use lipoic acid as a cofactor

• Its not clear whether a dietary deficiency of lipoic acid contributes to a disease state, so its not technically considered a vitamin

Folic acid derivatives (i.e. "folates") are acceptors and donors of one-carbon units for all oxidation levels of carbon (except for the most oxidized form - CO₂. See biotin above).

• The active coenzyme form is tetrahydrofolate (THF). Folate is reduced to THF by the action of dihydrofolate reductase.

• Three different oxidation states of carbon can bind to THF. These are oxidation states of -2 (methanol group), 0 (formaldehyde group) and +2 (formate group)

• These groups are attached to the THF molecule at either the N5 or N10 atom positions

• The biosynthetic pathways of methionine, homocysteine, purines, and thymine rely one one-carbon units being provided by THF.

• Hydroxylation of proline and lysine residues in collagen. Without these post-translational modifications the triple helix of collagen is unstable and connective tissue loses its integrity. This is the problem in the disease known as scurvy.

• Mobilization of iron, stimulation of immune system, anti-oxidant for scavenging of reactive free-radicals.

Vitamin A occurs as an ester (Retinyl ester), aldehyde (Retinal) or acidic form (Retinoic acid).

• It is a fat soluble vitamin, and is synthesized from isoprene building blocks

• Obtained directly from an animal diet, or synthesized from b-carotene provided by plants (carrots for example)

• It is essential to vision. Retinol transported to the eyes is oxidized by retinol dehydrogenase to produce trans-retinal. Trans-retinal is converted to 11-cis-retinal by retinal isomerase. The aldehyde group of retinal forms a Schiff base with a lysin of the protein opsin, to form rhodopsin (the light-sensitive pigment of vision).

• Vitamin A is essential for various biological processes - including fetal development and sperm development. But excessive vitamin A is toxic.

Cholecalciferol is produced in the skin of animals by the action of U.V. light on the precursor molecule 7-dehydrocholesterol.

• Ergocalciferol is produced by the action of U.V. light on the plant sterol ergosterol.

• Since humans can produce D3 from 7-dehydrocholesterol, vitamin D3 is technically not really a vitamin

• Cholecalciferol is really a prohormone. Derivatives of this compound regulate calcium and phosphate metabolism.

• Inadequate intestinal absorption of calcium and phosphate can result in demineralization of bones, and the disease Rickets.

a-Tocopherol is a potent antioxidant, however, molecular details of its function are not clearly understood.

Vitamin K is essential to the blood-clotting process. Vitamin K is required for the post-translational modification to produce g-carboxy glutamic acid from glutamic acid. Such modified residues can bind Ca²⁺, which is an essential part of the process in the clotting cascade.

• Prothrombin ("factor II"), and factors VII, IX and X are serine proteases that participate in a protease activation cascade that is involved in blood coagulation, and have g-carboxy glutamic acids in their structure