Content:

1. The most meaning chemical reactions
2. The principles of regulation of metabolic pathways

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The nearly significant chemic reactions

Metabolic pathways in human organism form vast network of more or less interconnected reactions that oftentimes share mutual intermediate products. Chemic conversions, which occur during the chemical reactions, tin be divided co-ordinate to the general mechanism, shared past all substances undergoing that particular reaction. For instance, decarboxylation reactions involve splitting off a CO2 molecule from the carboxyl group and its substrates include various carboxylic acids.

In this subchapter, we will speak about the most important types of chemical reactions with typical examples taken from human metabolic pathways.

Alcohols, carbonyl compounds and carboxylic acids

Alcohols, carbonyl compounds and carboxylic acids grade an important grouping of substances involved in many chemical reactions of intermediate metabolism.

Alcohols are characterized by the presence of OH- functional grouping. Depending on the number of these groups in the molecule, alcohols can by mono-, di- or polyhydric. Another division is based on the nature of a carbon atom to which an OH- grouping is fastened: principal (R-CHtwo-OH), secondary (R1-CH(OH)-R2) and third (C-RoneR2R3(OH)) alcohols.

Aldehydes and ketones together, for a group of carbonyl compounds. Their functional groups are –CHO and C=O, respectively.

Carboxylic acids, characterised by the presence of –COOH group, and their derivatives are probably the most of import members of this group of substances.

Alcohols, carbonyl compounds and carboxylic acids participate in many reactions – among the virtually significant are:

1) The formation of anions and acyls, derived from carboxylic acids

ii) Dehydrogenations and hydrogenations (oxidations and reductions)

3) Esterifications

1) The germination of anions and acyls, derived from carboxylic acids

Carboxyl grouping is capable of dissociation, the extent of which, for a particular acid, is expressed past dissociation constant. In full general, carboxylic acids belong to weak acids, which means that they dissociate only partially. The resulting anion (with -COO– group) is termed acetate.

Afterward splitting off the OH- group from carboxyl an acyl is formed.

2) Dehydrogenations and hydrogenations (oxidations and reductions)

Dehydrogenation is a chemic reaction leading to the elimination of –H atom from the molecules. The hydrogen atom obtained in this process tin can exist after used to create a proton gradient beyond the mitochondrial membrane in club to gain energy (ATP). The incorporation of the hydrogen into the molecule is termed hydrogenation. Hydrogenations and dehydrogenations occur during:

a) The oxidation of uncomplicated bonds to double bonds

b) The reciprocal conversions of alcohols – carbonyl compounds – carboxylic acids

a) The oxidation of elementary bonds to double bonds

The general reaction scheme is as follows:

-CH2-CH2– ↔ -CH=CH- + 2H+ + 2e–

Such reactions are abundant in Krebs bike, β-oxidation of fatty acids or desaturation reactions (producing unsaturated fatty acids).

b) The reciprocal conversions of alcohols – carbonyl compounds – carboxylic acids

This threesome of organic compounds forms a series that differ in the degree of oxidation (or reduction). Full general scheme of their interconversion is as follows (conversion towards the carbonyl compound and carboxylic acrid is oxidation, in opposite direction information technology is a reduction):

1. Primary alcohol ↔ aldehyde ↔ carboxylic acid

R-CHii-OH ↔ R-CHO ↔ R-COOH

2. Secondary alcohol ↔ ketone

Ri-CH(OH)-R2 ↔ Rone-CO-R2

3. 3rd alcohol – cannot be oxidised

As an case of oxidation, we tin can accept the conversion of glycerol-iii-phosphate to dihydroxyacetone phosphate (DHA-P), with FAD as a cofactor, through which a glycerol enters the metabolic pathways of glycolysis or gluconeogenesis (depending on the bodily needs of the organism).

3) Esterification

Esterification is a reaction betwixt carboxylic acrid and alcohol, creating an ester and a water molecule:

Ri-OH + R-COOH → R1–O-(C=O)-R + H2O

The well-nigh important carboxylic acids and derived anions and acetyls are summarised in the post-obit tables:

1) Saturated monocarboxylic acids
C Systematic proper name Mutual name Latin proper name Acyl Anion
one Methanoic Formic air conditioning. formicum Formyl Formate
ii Ethanoic Acerb air conditioning. aceticum Acetyl Acetate
three Propanoic Propionic ac. propionicum Propionyl Propionate
iv Butanoic Butyric air-conditioning. butyricum Butyryl  Butyrate
5 Pentanoic Valeric ac. valericum Valeryl Valerate
12 Dodecanoic Lauric ac. lauricum Lauryl Laurate
xvi Hexadecanoic Palmitic ac. palmiticum Palmitoyl Palmitate
eighteen Octadecanoic Stearic ac. stearicum Stearoyl Stearate
2) Saturated dicarboxylic acids
C Systematic proper name Common name Latin proper noun Acyl Anion
two Ethanedioic oxalic air conditioning. oxalicum Oxalyl Oxalate
three Propanedioic Malonic ac. malonicum Malonyl Malonate
4 Butanedioic Succinic ac. succinicum Succinyl Succinate
5 Pentanedioic Glutaric ac. glutaricum Glutaryl Glutarate
half-dozen Hexanedioic Adipic air conditioning. adipicum Adipoyl Adipate
3) Unsaturated monocarboxylic acids
C Systematic proper noun Mutual proper name Latin name Acyl Anion
18:1 cis- octadec-9-enoic Oleic air conditioning. oleicum Oleoyl Oleate
18:ii (ω-half dozen) cis,cis- octadeca-ix,12-dienoic Linoleic air-conditioning.linoleicum Linoloyl Linolate
xviii:iii (ω-iii) cis,cis,cis- octadeca-9,12,15-trienoic Linolenic ac.linolenicum Linolenoyl Linolenate
20:4 (ω-vi) cis,cis,cis,cis- eicosa-5,8,11,xiv-tetraenoic Arachidonic ac. arachidonicum Arachidonyl Arachidonate
four) Unsaturated dicarboxylic acids
C Systematic proper name Common proper noun Latin name Acyl Anion
4 cis- butenedioic Maleic ac. maleicum Maleinyl Maleinate
4 trans- butenedioic Fumaric ac. fumaricum Fumaroyl Fumarate
5) Derivatives of carboxylic acids
C Systematic proper noun Mutual name Latin proper noun Acyl Anion
3 2-oxopropanoic Pyruvic ac. pyruvicum Pyruvyl pyruvate
3 2-hydroxypropanoic Lactic air-conditioning. lacticum Lactoyl Lactate
4 iii-oxobutanoic Acetoacetic Acetoacetyl Acetoacetate
4 3-hydroxybutanoic β-hydroxybutyric β-hydroxybutyrate
4 hydroxybutanedioic Malic ac. malicum Maloyl Malate
4 oxobutanedioic Oxaloacetic Oxalacetate
5 two-oxopentanedioic α-ketoglutaric α-ketoglutaryl (2-oxoglutaryl) α-ketoglutarate (ii-oxoglutarate)
6 two-hydroxypropane-ane,two,iii-tricarboxylic Citric ac. citricum Citrate

Hydroxy acids and oxo acids

A mutual conversion of hydroxy acids (containing, apart from –COOH group, -OH grouping as well, replacing one of the hydrogen atoms in the chain) and oxo acids (also called keto acids, which contain both –COOH and =O grouping replacing i of the hydrogen atoms in the concatenation) is a common phenomenon of metabolic pathways. Hydroxy acids oxidise to oxoacids or vice versa, oxoacids reduce to hydroxy acids as depicted in the following examples:

Another phenomenon occurring in metabolism is keto-enol tautomerism that refers to a chemical equilibrium betwixt two forms of organic compounds: keto– (or oxo-) class, containing oxygen bound by double bond (=O) and enol form, containing double bail betwixt two carbon atoms together with –OH grouping fastened to one of them (-C=C-OH). Their interconversion involves the movement of alpha hydrogen (or proton) and the shifting of bonding electrons (seen a as shift of double and its side by side single bond).

Amino acids and oxo acids

Amino and oxoacids represent a substitution derivatives of carboxylic acids. Molecules of amino acids contain the –COOH group together with -NH2 group whereas oxoacids accept =O group. When interconverting, these two groups exchange the -NH2 and =O groups. There be two main types of these reactions:

one) Transaminations

2) Oxidative deaminations

i) Transaminations

In this blazon of reactions, amino acid acts as a -NHii group donor that is accepted by oxoacid. The oxoacids converts to amino acrid and amino acids becomes oxoacid.

AA1 + OxoA2 ↔ OxoA1 + AAii

two) Oxidative deamination

In this reaction, an oxoacids is formed past elimination the -NHii group from amino acids. NH2– is released every bit an ammonia (NH3). Oxidative deaminations are important reactions through which amino acids begin their degradation process. They mainly occur in liver and the produced ammonia enters the procedure of urea synthesis.

This reaction is catalysed past glutamate dehydrogenase.

Decarboxylations and carboxylations

Decarboxylation is a chemic reaction that involves the elimination of the whole carboxy group (released as a molecule of CO2 ) and its replacement with proton. It is a office of several metabolic pathways:

1) The conversion of amino acids to biogenic amines (e.thousand. during the synthesis of many neurotransmitters)

Synteza katecholaminu ENG-01

two) Dehydrogenations of two-oxoacids – pyruvate dehydrogenase reaction and two reactions of Krebs cycle

Carboxylation takes a reversed course, information technology involves an incorporation of –COOH group into the molecule, for example:

one) Fatty acids synthesis

ii) Gluconeogenesis

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The principles of regulation of metabolic pathways

Regulatory reactions of metabolic pathways are usually localized somewhere near the beginning of the particular pathway – very oft they are the beginning irreversible reaction. The reason is a tendency to reduce the waste of resources and unnecessary production of intermediates (that would occur, when the pathway would not be halted at the kickoff but later several steps).

The regulatory enzyme is often present at low concentration (lower compared to the concentrations of other enzymes involved in the pathway) that limits its function. Furthermore, the enzyme usually belongs to the group of allosteric enzyme, operating according to "all-or-none" principle. The existence of a concentration limit (above which the reaction soon reaches the maximum speed but below which information technology virtually does not occur) is quite advantageous for regulation.

Regulation of metabolic pathways is based on, as is also the case of other regulated processes within the body, the principle of feedback. The intermediates or the end products of reactions affect the grade of the reaction.

one) Negative feedback

The deviation from a certain value (fix point) triggers a chain of reaction, which brings the system back to its previous state. Negative feedback is therefore the source of the stability (by constantly bringing the organisation back to the set up bespeak) and is the basic regulatory mechanism in almost all metabolic processes.

Every bit an instance we can take an enzyme ALA-synthase I (a regulatory enzyme of heme synthesis, localised in liver). When the concentration of the stop product (heme) is high, it slows (through negative feedback) the whole pathway downwardly.

ii) Positive feedback

The deviation from the value of set point, leads in this case to the chain of reactions that further deepen the departure. The arrangement is at risk from the creation of fell circle, where each further increase of divergence speeds up the whole process, until the instability of the arrangement reaches the indicate where it collapses.

The widely known example of positive feedback in our bodies is represented by oxytocin. Oxytocin is a peptide hormone produced in hypothalamic nuclei that (apart from other functions) causes the wrinkle of smooth muscles of uterus during delivery. Every wrinkle activates mechanoreceptors lying in the uterus wall, which acts as a stimulus for farther secretion of oxytocin. That is why its outcome increases until both baby and placenta are born and the pressure in the uterus drops.

Regulatory step is affected past:

ane) Change of accented concentration of enzyme (the corporeality of the enzyme)

Information technology can be regulation through the changes in transcription and translation of the detail enzyme. Induction activates and repression inhibits a cistron expression. Instance is the substrate induction, when the synthesis of a certain factor is induced past the presence of its substrate.

2) Modulation of the activity of an already existing enzyme (the activity of enzyme)

The activity of enzyme can be affected by:

a) Presence of activator or inhibitors

b) Covalent modification of enzyme molecule (phosphorylations / dephosphorylation, changing proenzymes into the active forms, …)

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Subchapter Writer: Petra Lavríková

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