Metabolic Pathways

Illustration is major pathways in a tapeworm. i.e Thought Icon   NB for the best possible explanations see Alberts Essential Biology p 465

For Food breakdown--

Food Molecules are Broken down in Three Stages

The proteins, lipids, and polysaccharides that make up most of the food we eat must be broken down into smaller molecules before our cells can use them—either as a source of energy or as building blocks for other molecules. This breakdown process—which uses enzymes to degrade complex molecules into simpler ones—is dubbed catabolism. Catabolism must act on food taken in from outside, but not on the macromolecules inside our own cells. Therefore stage 1 in the enzymatic breakdown of

food molecules—digestion—occurs either outside cells (in our intestine) or in a specialized organelle within cells called the lysosome. A membrane that surrounds the lysosome keeps its digestive enzymes separated from the cytosol .

Digestive enzymes reduce the large polymeric molecules in food into their monomeric subunits: proteins into amino acids, polysaccharides into sugars, and fats into fatty acids and glycerol. After digestion, the small organic molecules derived from food enter the cytosol of a cell, where their gradual oxidation begins.  This oxidation occurs in two further stages: stage 2 starts in the cytosol and ends in mitochondria, while stage 3 is con ned to the mitochondria.

In stage 2 of cellular catabolism, a chain of reactions called glycolysis converts each molecule of glucose into two smaller molecules of pyruvate. Sugars other than glucose can also be used after being rst converted to one of the sugar intermediates in this glycolytic pathway. During the formation of pyruvate, two types of activated carrier molecules are produced: ATP and NADH. The pyruvate is then transported from the cytosol into the mitochondrion’s large, internal compartment or matrix. There a giant enzyme complex converts each pyruvate molecule into CO2 plus acetyl CoA, another of the activated carrier molecules,  Large amounts of acetyl CoA are also produced by the stepwise breakdown and oxidation of fatty acids derived from fats.

Stage 3 of the oxidative breakdown of food molecules takes place entirely in mitochondria. The acetyl group in acetyl CoA is transferred to a molecule called oxaloacetate to form citrate, which enters a series of reactions called the citric acid cycle. The transferred acetyl group is oxidized to CO2 in these reactions, and large amounts of the high-energy electron carrier NADH are generated. Finally, the high-energy electrons from NADH are passed along a series of enzymes within the mitochondrial inner membrane called an electron-transport chain, where the energy released by their transfer is used to drive a process that produces ATP and consumes molecular oxygen (O2 gas). It is in these final steps that most of the energy released by oxidation is harnessed to produce most of the cell’s ATP.

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<img src="/f754ae04-87c9-5739-a1e2-3b588b6e95e6.png"/>     Krebs Cycle <img src="/72e7ee3b-4216-58cd-8d7b-500fe0d0ea66.png"/>

Crosstalk between metabolic pathways. The network diagram represents the number of enzymes shared between pathways. Each pathway is represented by a node. Connections (edges) between these nodes represent the number of enzymes common to each pathway. Nodes are colored according to their superclass category; node size indicates the number of enzymes in that pathway; and thickness of edges indicate the number of enzymes common to each pathway (see inset keys).

Schematic of the central metabolic pathways of E. coli.

2nd diagram--    E. coli metabolic pathways showing the interrelationships between different genes and global regulators. Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively.

Illustration of conversion of Glycerol from Oil products to D-Lactate   in E Coli 

Lactic acid has gained importance in the detergent industry the last decade. It is a good descaler, soap-scum remover, and a registered anti-bacterial agent. It is also economically beneficial as well as part of a trend toward environmentally safer and natural ingredients.

General Remarks for Part 1 and 2   Biochemical Pathways.

Enzymes are shown in blue

Coenzymes are shown in red, other reaction participants in black.

Color of the arrows shows type of organism in which the reaction was observed or is likely to occur:

a black arrow general biochemical pathways, a blue arrow animals,

a green arrow higher plants, a red arrow unicellular organisms

Dashed arrows are used for catabolic pathways, continuous lines for anabolic and bidirectional (amphibolic) pathways. Points on both ends of arrows indicate reversibility. An orange arrow alongside of it shows the preferred direction.

Regulatory effects are shown in orange. Metal ions and similar activators are located next to the reaction arrow. Effectors with a "fast" regulation of the flow (e. g. by allosteric mechanisms) have a continuous orange arrow coming from the side, those with a "slow" regulation (e. g. by induction or repression of the enzyme synthesis) a dashed orange arrow. a red plus = increase, a red minus = decrease of enzymatic activity. Roman numerals indicate, that only one of multiple enzymes is regulated this way. Regulators shown in parentheses are effective in only one group or species of organisms.

Compounds enclosed in black lined, sharp edged boxes occur in several places in the chart. Coenzymes or compounds with very simple structures are not in boxes. Boxes with rounded corners are sometimes used in part 2 to indicate enzymes (inactive in black, active in blue). Protein sequences are abbreviated by a wavy line.

Compound names in orange boxes indicate excretory or end- products of metabolism.

For ionized compounds, the name of the salt is used to correspond with enzyme names. Structural formulas, however, show the free acid or base, since frequently at physiological pH different grades of ionization occur simultaneously. Therefore, participation of H+ or OH- is not shown (except in NADH + H+ and NADPH + H+.

Organic phosphate is abbreviated to -P, inorganic phosphate to Pi, pyrophosphate to PPi.

All amino acids can be attached to their respective tRNAs by the appropriate ligases. Some of these reactions are shown here as examples.

Cellular surface membranes, membranes of the endoplasmic reticulum, of the Golgi apparatus etc. have approximately the same thickness. For graphical reasons, however, they have been drawn in part 2 with different widths.

While notations for genes are written with small letters (e.g. raf), the respective gene products (proteins) are written with capitalized first letters (e.g. Raf). Another way of designating them is p74c-raf, indicating the molecular weight (in kD) and the origin (c = cellular, v = virus)

Intracellular Metabolism

<img src="/49244c5f-d82d-5d02-a912-8269e6bb84fc.png"/>             <img src="/f43840f8-4de5-58ba-b41d-7cf1e0a03d0b.png"/>     Warburg effect Signalling pathway.

For details of Glycolysis and movie see p 451 and 452 of Albert's  Essential Cell Biology.          Warburg Effect---- see above right.  Most mammalian cells use glucose as a fuel source. Glucose is metabolized by glycolysis in a multistep set of reactions resulting in the creation of pyruvate. In typical cells under normal oxygen levels, much of this pyruvate enters the mitochondria where it is oxidized by the Krebs Cycle to generate ATP to meet the cell’s energy demands. However, in cancer cells or other highly proliferative cell types, much of the pyruvate from glycolysis is directed away from the mitochondria to create lactate through the action of lactate dehydrogenase (LDH/LDHA)—a process typically reserved for the low oxygen state. Lactate production in the presence of oxygen is termed “aerobic glycolysis” or the Warburg Effect. -

Metabolic Pathways

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