by Benjamin Bunting BA(Hons) PGCert
Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.
Question: What are catabolic pathways?
Answer: Catabolism pathways are metabolic pathways that break down complex molecules into simpler ones, releasing energy in the process.
These pathways are responsible for the breakdown of carbohydrates, fats, and proteins in the body to produce energy for cellular processes.
An Overview of Catabolic Pathways
In this article we will take a closer look at metabolic pathways - linked chemical reactions that produce something and transform it into another substance.
These pathways consist of linked reactions which feed off each other, taking in products of previous reactions and turning them into something new.
These chemical reactions start by taking in starting molecules and turning them into end products via various catabolic (degradative) or anabolic (building up) processes.
Catabolic reactions refer to those which break down large molecules into smaller ones; anabolic ones involve building larger ones up from simpler components.
All biological reactions require and release energy; many of them can be catalyzed by proteins called enzymes.
Breakdown energy is converted to Adenosine Triphosphate, or ATP, the energy currency of cells. This can then be used for anabolic processes; stored as fat or nucleic acids for storage or used to power anaerobic metabolism.
Most organisms capture energy from the environment to power their cellular functions, most commonly through catabolic reactions such as cellular respiration which breaks down glucose into energy for use by cells.
Glycolysis produces pyruvate that can enter either the citric acid cycle and oxidative phosphorylation pathways. Or alternatively be routed down the pentose phosphate pathway for production of five-carbon sugars that are necessary for DNA and RNA synthesis.
Furthermore, this pathway produces acetyl coa that can then be converted to ATP via mitochondrial oxidative phosphorylation systems or electron transport systems.
Catabolic Pathways - Breaking Down Molecules for Energy
Organisms need energy for daily functioning. Organisms harvest potential energy stored in molecules of carbon and oxygen (CO2 and H2O), harness it, and create ATP from it via cellular respiration.
One key step involves breaking down sugar molecules into VFAs and CO2. Glucose is one such source that can either be utilized directly by plants themselves or consumed by bacteria which convert it to energy via fermentation.
Both processes involve metabolic pathways - interlinked chemical processes that feed off each other before culminating in production of an end product - something glucose plays a significant role.
Cellular metabolism can be divided into catabolic and anabolic pathways. Catabolic pathways involve degradative chemical reactions that break complex molecules down into smaller ones; examples of such pathways include glycolysis, the citric acid cycle and neurotransmitter deamination via oxidative deamination.
These pathways supply both energy and building blocks that will eventually be used to assemble larger macromolecules through anabolic reactions.
For instance, breaking down glucose via glycolysis produces two molecules of ATP that can then be used in biosynthesis to form monosaccharides, nucleotides or amino acids.
Feedback inhibition connects various steps of these pathways. For instance, phosphofructokinase catalyzes a reaction in the citric acid cycle that produces more ATP than it needs; this energy is then recycled through subsequent reactions in its cycle.
The Role of IGFs in Catabolism
Catabolic processes entail disassembling complex organic molecules into smaller components. Within the body, this usually means breaking down polysaccharides such as starch and glycogen into monosaccharides for energy use; proteins into amino acids; and nucleic acids into nucleotides.
IGF1 plays multiple roles on metabolism. Recent studies have demonstrated its deficiency increases insulin resistance, impairs lipid and glucose metabolism and increases oxidative stress in tissues.
Unfortunately, its role as an anabolic factor is further complicated by the fact that hepatocytes serve both as sources of IGF1 as well as receptors for it.
Proteins are among the most abundant macromolecules found in organisms, serving numerous essential roles ranging from structural support and transport, regulatory processes and more.
Their production involves several steps involving transcription and translation. During transcription genetic information encoded as messenger RNA leaves the nucleus for transport into cytoplasm where it attaches to a protein-synthesis machine.
This is called ribosome where translation takes place to produce chain of amino acids which later fold into specific protein structures; this complex biological event must be carefully managed by specialists.
Proteins are composed of amino acid monomers produced in cells by synthesizing glucose or other carbon sources into amino acid monomers.
These are then combined by enzymes to form polypeptide chains which then fold into secondary, tertiary and quaternary structures before being transported throughout cells to fulfill their roles.
A significant amount of metabolic energy consumed by cells goes toward maintaining this process - up to 25% according to some estimates!
Severe burns can induce a catabolic state characterized by muscle wasting and decreased net protein synthesis, according to previous studies.
Nutritional support and pharmaceutical interventions with insulin-like growth factor (IGF) or IGFBP-3 have been found to attenuate this muscle catabolism; however, human use of these agents may produce unwanted side effects.
The purpose of one study was to assess the effect of combining human IGF-1/IGFBP-3 on skeletal muscle metabolism in severely burned children.
29 patients were administered doses of IGF-1/IGFBP-3 at 0, 0.5, 1, 2, or 4 mg/kg/day and their net protein balance and fractional synthetic rates assessed before and after treatment with IGF-1/IGFBP-3.
Its effect improved net protein synthesis but did not alter glucose metabolism or plasma urea levels significantly - these changes did not impact gluconeogenesis at all.
High protein intakes have long been linked to decreased cancer rates and mortality; the mechanism remains unexplored, however.
We have previously demonstrated how GHR-IGF-1 and mTOR pathways may play a role in increasing longevity benefits associated with eating more proteins.
However, in a recent survey of middle aged people it was discovered that even though higher protein consumption reduces risks of cancer and death; it actually increases both all-cause mortality as well as cause-specific deaths.
Insulin and IGF-1 play an intricate role in glucose and lipid metabolism by acting in concert to produce an integrated response . Of all the genes regulated by IGF-1 directly, those related to metabolic enzymes are particularly affected.
Partial IGF-1 deficiency reduces hepatic expression of these enzymes causing deregulation in glucose and lipid metabolism as a result of reduced liver expression of these enzymes leading to deregulation and thus contributing to metabolic syndrome development.
Blood serum values for glucose, triglycerides and cholesterol as well as the level of MDA were examined in untreated Hz mice as well as CO and Hz + IGF-1 animals.
Untreated Hz mice demonstrated significant increases in triglycerides and cholesterol as well as significant decreases in HDL levels compared to CO animals.
With substitution of IGF-1 these parameters returned back to similar levels found in CO animals.
IGF-1 also helped normalize expression levels for three enzymes involved with hyperlipidemia such as g6pc (glucose-6-phosphatase catalytic), Pdk1 (phosphoenolpyruvate carboxykinase 1, cytosolic) and ACLY (ATP citratelyase), thus decreasing hyperlipidemia, hyperglycemia as well as peroxidative liver damage caused by free radicals.
Reducing expression of acetyl-CoA acetyltransferase 1 (acetyl-CoA acetyltransferase 1), another hepatic enzyme involved in lipid metabolism was also observed in Hz mice compared with CO animals.
This finding was confirmed through microarray analysis and RT-q PCR which demonstrated this trend.
Substitution with IGF-1 increased expression levels hepatically suggesting low IGF-1 levels circulating among Hz mice were responsible for deregulation of lipid metabolism.
IGF-1 levels decline with age, which has been linked with increases in dyslipidemia (cholesterol and triglycerides) as well as hyperglycemia and insulin resistance resulting in liver damage and mitochondrial dysfunction.
The research indicates that replacing IGF-1 with exogenous IGF-1 at very low doses restores normal levels of these parameters thereby decreasing dyslipidemia, hyperglycemia, and diminishing oxidative liver damage. Suggesting this approach as a viable therapeutic strategy for MetS.
Carbohydrate metabolism refers to a series of biochemical pathways that break down fuel molecules into energy-rich molecules such as ATP, GTP and reduced nicotinamide adenine dinucleotide dinucleotide phosphate (NADH2).
Or reduced flavin adenine dinucleotide dinucleotide dinucleotide dinucleotide dinucleotide dinucleotide dinucleotide (NADPH2).
These molecules can be produced through glycolysis, citric acid cycle or pentose phosphate pathway processes; mammals regulate carb metabolism via insulin/glucagon hormones.
Insulin is a polypeptide hormone composed of two chains linked by disulfide bonds. Released by the pancreas in response to food consumption, insulin stimulates glycolysis by binding with its receptors on cells.
Once activated, insulin increases glucose transport into muscle cells and adipose tissue while simultaneously stopping protein degradation for increased protein synthesis.
Glycogenesis, or the production of glycogen in liver and muscle, is controlled by insulin.
Not all glucose that enters our bodies can be effectively processed. Any excess is stored as glycogen in muscle and adipose tissues for later release during fasting or exercise, or broken down to produce glucose via gluconeogenesis and citric acid cycle reactions stimulated by insulin or growth hormone.
In turn these reactions are inhibited by glucagon or epinephrine.
Insulin/glucagon regulation of carb metabolism is complex. When blood sugar levels are elevated, insulin secreted from b cells promotes glycolysis to lower glucose concentration in most cells of the body while inhibiting gluconeogenesis and breakdown of glycogen by the liver.
Conversely, when blood sugar levels decrease glucagon promoted by a cells triggers production of glucose from liver tissue and muscle, and releases it back into circulation through breaking down glycogen in liver and breaking it down to release more glucose into circulation.
Carbs serve a crucial signaling role in cells by attaching to proteins through N-glycosidic bonds and forming glycoproteins oligosaccharides, or glycopeptides.
Posttranslationally these glycoproteins can be modified through posttranslational addition of various glucosamine, galactose or N-acetylgalactosamine residues found within endoplasmic reticulum and Golgi apparatus environments that alter their structural integrity as well as alter their activity and stability.
IGFs can stimulate cell and tissue growth in muscles and bones, as well as play an essential role in fat metabolism regulation. From stimulating lipid synthesis to increasing transport to mitochondria, to switching over to glycolytic metabolism to help build muscle mass.
IGFs exert their growth-promoting effects regardless of their serum concentration.
However, their actions can be adjusted by binding to proteins known as IGFBPs.
There are six members in this family, which vary in their ability to bind IGFs and regulate their activities; most extracellular environments contain most IGFs bound with either IGFBP-3 or -4 in ternary complexes that increase availability by protecting from degradation and reaching receptors more quickly.
These compounds can bind and inhibit IGF receptors, interfering with their actions.
Alternately, they may promote cell transformation and tumor growth. For instance, IGF-1 helps promote lamellipodia formation, an indicator of cancer cells that is linked with increased migration and metastasis.
IGF-1 may promote type 1 diabetes in mice when its effects cause their immune systems to attack beta cells of the pancreas that produce insulin, though studies have demonstrated that when levels of IGF-1 are kept at lower levels it promotes longevity, reduces oxidative stress and atherosclerosis progression is lessened.
IGF-1 is an essential hormone in our bodies, but its levels may become harmful when they rise too far.
Therefore, eating a well-balanced diet to maintain steady IGF-1 levels is key; intense/strenuous exercise may also help with this goal, although as soon as your body adjusts it may start decreasing it again - for this reason alone it is advised not to take IGF-1 supplements without first consulting your physician; especially if you have prediabetes or diabetes.
IGFs circulate in extracellular fluid bound to binding proteins called IGFBPs that act classically to limit access of IGFs to their receptors and modulate IGF actions.
Furthermore, genetically modified animals provide new insights into how these IGFBPs interact with IGFs to regulate growth and metabolism.
IGF system is complex and regulates multiple cellular processes in an endocrine, autocrine and paracrine fashion.
It plays a key role in cell growth, differentiation and metabolism while many of its effects overlap with those of insulin/INSR.
IGF-1 is a key anabolic hormone that promotes protein synthesis in skeletal muscles during periods of prolonged fasting or following meals with high protein intake, likely by binding with IGFBP-2 as a delivery and linkage molecule, increasing its affinity with IGF-receptor complex and thus providing easy access to receptor sites on receptor cells.
IGF-1 acts to inhibit both hepatic glucose production and pituitary GH secretion in humans and mice.
Furthermore, its actions on muscle free fatty acid metabolism and renal gluconeogenesis appear to play an integral part in increasing insulin sensitivity in type 2 diabetes; although its exact role in increasing it sensitivity remains uncertain.