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What are these pathways called in Biology?

What are these pathways called in Biology?


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Considering the pentose phosphate pathway and the sulfate reduction pathway in bacteria;

What are these types of reactions called in biology? Bio degradation reactions or bio transformation reactions or something else? I wish to know whether there is a generalized names for these types of pathways.


Short answer
Assuming you wish to have a common name for both of these (widely differing!) pathways I basically agree with @Chris, and I would go for general terminology, namely metabolic pathways.

Background
The pentose-phosphate pathway is neither anabolic nor catabolic so those terms won't do. The pentose-phosphate pathway is, however, closely linked to general metabolism to supply the body with C5 sugars. So metabolic pathway sounds right to me.

The other pathway is a sulfate reduction pathway, which is an anaerobic respiration pathway that uses sulfate as the terminal electron acceptor instead of oxygen. It is an entirely different pathway. However, it too is neither catabolic or anabolic, but still closely linked to metabolism. Hence, metabolic pathway is applicable here too.


What are these pathways called in Biology? - Biology

An array of approximately 20 types of soluble proteins, called a complement system, functions to destroy extracellular pathogens. Cells of the liver and macrophages synthesize complement proteins continuously these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the antibody response of the adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. Binding of complement proteins occurs in a specific and highly regulated sequence, with each successive protein being activated by cleavage and/or structural changes induced upon binding of the preceding protein(s). After the first few complement proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement proteins.

Complement proteins perform several functions. The proteins serve as a marker to indicate the presence of a pathogen to phagocytic cells, such as macrophages and B cells, and enhance engulfment this process is called opsonization. Opsonization refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte. Certain complement proteins can combine to form attack complexes that open pores in microbial cell membranes. These structures destroy pathogens by causing their contents to leak, as illustrated in Figure 1.

Figure 1. Click for a larger image. The classic pathway for the complement cascade involves the attachment of several initial complement proteins to an antibody-bound pathogen followed by rapid activation and binding of many more complement proteins and the creation of destructive pores in the microbial cell envelope and cell wall. The alternate pathway does not involve antibody activation. Rather, C3 convertase spontaneously breaks down C3. Endogenous regulatory proteins prevent the complement complex from binding to host cells. Pathogens lacking these regulatory proteins are lysed. (credit: modification of work by NIH)


7.6 Connections of Carbohydrate, Protein, and Lipid Metabolic Pathways

In this section, you will explore the following question:

  • How do carbohydrate metabolic pathways, glycolysis, and the citric acid cycle interrelate with protein and lipid metabolism pathways?

Connection for AP ® Courses

The breakdown and synthesis of carbohydrates, proteins, lipids, and nucleic acids connect with the metabolic pathways of glycolysis and the citric acid cycle but enter the pathways at different points. Thus, these macromolecules can be used as sources of free energy.

Information presented and the examples highlighted in the section support concepts and Learning Objectives outlined in Big Idea 2 of the AP ® Biology Curriculum Framework, as shown in the table. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP ® Biology course, an inquiry-based laboratory experience, instructional activities, and AP ® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.

Essential Knowledge 2.A.2 Organisms capture and store free energy for use in biological processes.
Science Practice 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices.
Learning Objective 2.5 The student is able to construct explanations of the mechanisms and structural features of cells that allow organisms to capture, store, or use free energy.
Essential Knowledge 2.A.1 All living systems require constant input of free energy.
Science Practice 6.1 The student can justify claims with evidence.
Learning Objective 2.2 The student is able to justify a scientific claim that free energy is required for living systems to maintain organization, to grow or to reproduce, but that multiple strategies exist in different living systems.

Teacher Support

Discuss with students how metabolic reactions include both the breakdown of molecules and the synthesis of larger molecules. For example as discussed in Anatomy and Physiology here.

Metabolic processes are constantly taking place in the body. Metabolism is the sum of all of the chemical reactions that are involved in catabolism and anabolism. The reactions governing the breakdown of food to obtain energy are called catabolic reactions. Conversely, anabolic reactions use the energy produced by catabolic reactions to synthesize larger molecules from smaller ones, such as when the body forms proteins by stringing together amino acids. Both sets of reactions are critical to maintaining life.

Because catabolic reactions produce energy and anabolic reactions use energy, ideally, energy usage would balance the energy produced. If the net energy change is positive (catabolic reactions release more energy than the anabolic reactions use), then the body stores the excess energy by building fat molecules for long-term storage. On the other hand, if the net energy change is negative (catabolic reactions release less energy than anabolic reactions use), the body uses stored energy to compensate for the deficiency of energy released by catabolism.

Have students create a visual representation of the interaction of various metabolic pathways. For example:

The Science Practice Challenge Questions contain additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards:
[APLO 2.5][APLO 2.15][APLO 3.20][APLO 1.5][APLO 1.26][APLO 4.18]

You have learned about the catabolism of glucose, which provides energy to living cells. But living things consume more than glucose for food. How does a turkey sandwich end up as ATP in your cells? This happens because all of the catabolic pathways for carbohydrates, proteins, and lipids eventually connect into glycolysis and the citric acid cycle pathways (see Figure 7.18). Metabolic pathways should be thought of as porous—that is, substances enter from other pathways, and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways.

Connections of Other Sugars to Glucose Metabolism

Glycogen, a polymer of glucose, is an energy storage molecule in animals. When there is adequate ATP present, excess glucose is shunted into glycogen for storage. Glycogen is made and stored in both liver and muscle. The glycogen will be hydrolyzed into glucose 1-phosphate monomers (G-1-P) if blood sugar levels drop. The presence of glycogen as a source of glucose allows ATP to be produced for a longer period of time during exercise. Glycogen is broken down into G-1-P and converted into G-6-P in both muscle and liver cells, and this product enters the glycolytic pathway.

Sucrose is a disaccharide with a molecule of glucose and a molecule of fructose bonded together with a glycosidic linkage. Fructose is one of the three dietary monosaccharides, along with glucose and galactose (which is part of the milk sugar, the disaccharide lactose), which are absorbed directly into the bloodstream during digestion. The catabolism of both fructose and galactose produces the same number of ATP molecules as glucose.

Connections of Proteins to Glucose Metabolism

Proteins are hydrolyzed by a variety of enzymes in cells. Most of the time, the amino acids are recycled into the synthesis of new proteins. If there are excess amino acids, however, or if the body is in a state of starvation, some amino acids will be shunted into the pathways of glucose catabolism (Figure 7.17). Each amino acid must have its amino group removed prior to entry into these pathways. The amino group is converted into ammonia. In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule. Thus, urea is the principal waste product in mammals, produced from the nitrogen originating in amino acids, and it leaves the body in urine.

The carbon skeletons of certain amino acids (indicated in boxes) derived from proteins can feed into the citric acid cycle. (credit: modification of work by Mikael Häggström)

Connections of Lipid and Glucose Metabolisms

The lipids that are connected to the glucose pathways are cholesterol and triglycerides. Cholesterol is a lipid that contributes to cell membrane flexibility and is a precursor of steroid hormones. The synthesis of cholesterol starts with acetyl groups and proceeds in only one direction. The process cannot be reversed.

Triglycerides are a form of long-term energy storage in animals. Triglycerides are made of glycerol and three fatty acids. Animals can make most of the fatty acids they need. Triglycerides can be both made and broken down through parts of the glucose catabolism pathways. Glycerol can be phosphorylated to glycerol-3-phosphate, which continues through glycolysis. Fatty acids are catabolized in a process called beta-oxidation that takes place in the matrix of the mitochondria and converts their fatty acid chains into two carbon units of acetyl groups. The acetyl groups are picked up by CoA to form acetyl CoA that proceeds into the citric acid cycle.

Evolution Connection

Pathways of Photosynthesis and Cellular Metabolism

The processes of photosynthesis and cellular metabolism consist of several very complex pathways. It is generally thought that the first cells arose in an aqueous environment—a “soup” of nutrients—probably on the surface of some porous clays. If these cells reproduced successfully and their numbers climbed steadily, it follows that the cells would begin to deplete the nutrients from the medium in which they lived as they shifted the nutrients into the components of their own bodies. This hypothetical situation would have resulted in natural selection favoring those organisms that could exist by using the nutrients that remained in their environment and by manipulating these nutrients into materials upon which they could survive. Selection would favor those organisms that could extract maximal value from the nutrients to which they had access.

An early form of photosynthesis developed that harnessed the sun’s energy using water as a source of hydrogen atoms, but this pathway did not produce free oxygen (anoxygenic photosynthesis). (Early photosynthesis did not produce free oxygen because it did not use water as the source of hydrogen ions instead, it used materials like hydrogen sulfide and consequently produced sulfur). It is thought that glycolysis developed at this time and could take advantage of the simple sugars being produced, but these reactions were unable to fully extract the energy stored in the carbohydrates. The development of glycolysis probably predated the evolution of photosynthesis, as it was well suited to extract energy from materials spontaneously accumulating in the “primeval soup.” A later form of photosynthesis used water as a source of electrons and hydrogen, and generated free oxygen. Over time, the atmosphere became oxygenated, but not before the oxygen released oxidized metals in the ocean and created a “rust” layer in the sediment, permitting the dating of the rise of the first oxygenic photosynthesizers. Living things adapted to exploit this new atmosphere that allowed aerobic respiration as we know it to evolve. When the full process of oxygenic photosynthesis developed and the atmosphere became oxygenated, cells were finally able to use the oxygen expelled by photosynthesis to extract considerably more energy from the sugar molecules using the citric acid cycle and oxidative phosphorylation.


Regulators of the secretory pathway have distinct inputs into single-celled branching morphogenesis and seamless tube formation in the Drosophila trachea

Biological tubes serve as conduits through which gas, nutrients and other important fluids are delivered to tissues. Most biological tubes consist of multiple cells connected by epithelial junctions. Unlike these multicellular tubes, seamless tubes are unicellular and lack junctions. Seamless tubes are present in various organ systems, including the vertebrate vasculature, C.elegans excretory system, and Drosophila tracheal system. The Drosophila tracheal system is a network of air-filled tubes that delivers oxygen to all tissues. Specialized cells within the tracheal system, called terminal cells, branch extensively and form seamless tubes. Terminal tracheal tubes are polarized the lumenal membrane has apical identity whereas the outer membrane exhibits basal characteristics. Although various aspects of membrane trafficking have been implicated in terminal cell morphogenesis, the precise secretory pathway requirements for basal and apical membrane growth have yet to be elucidated. In the present study, we demonstrate that anterograde trafficking, retrograde trafficking and Golgi-to-plasma membrane vesicle fusion are each required for the complex branched architecture of the terminal cell, but their inputs during seamless lumen formation are more varied. The COPII subunit, Sec 31, and ER exit site protein, Sec16, are critical for subcellular tube architecture, whereas the SNARE proteins Syntaxin 5, Syntaxin 1 and Syntaxin15 are required for seamless tube growth and maintenance. These data suggest that distinct components of the secretory pathway have differential contributions to basal and apical membrane growth and maintenance during terminal cell morphogenesis.


Examples of Catabolism

Carbohydrate and Lipid Catabolism

Almost all organisms use the sugar glucose as a source of energy and carbon chains. Glucose is stored by organisms in larger molecules called polysaccharides. These polysaccharides can be starches, glycogen, or other simple sugars like sucrose. When an animal’s cells need energy, it sends signals to the parts of the body that store glucose, or it consumes food. Glucose is released from the carbohydrates by special enzymes, in the first part of the catabolism. The glucose is then distributed into the body, for other cells to use as energy. The catabolic pathway glycolysis then breaks glucose down even further, releasing energy that is stored in ATP. From glucose, pyruvate molecules are made. Further catabolic pathways create acetate, which is a key metabolic intermediate molecule. Acetate can become a wide variety of molecules, from phospholipids, to pigment molecules, to hormones and vitamins.

Fats, which are large lipid molecules, are also degraded by the metabolism to produce energy and to create other molecules. Similar to carbohydrates, lipids are stored in large molecules, but can be broken down into individual fatty acids. These fatty acids are then converted through beta-oxidation into acetate. Again, acetate can be used by the anabolism, to produce larger molecules, or as part of the citric acid cycle which drives respiration and ATP production. Animals use fats to store large amount of energy for future use. Unlike starches and carbohydrates, lipids are hydrophobic, and exclude water. In this way, a lot of energy can be stored without the heavy weight of water slowing the organism down.

Most catabolic pathway are convergent in that they end in the same molecule. This enables organisms to consume and store energy in a variety of different forms, while still being able produce all the molecules it needs in the anabolic pathways. Other catabolic pathways, such as protein catabolism discussed below, create different intermediate molecules are precursors, known as amino acids, to build new proteins.

Protein Catabolism

If no source of glucose is present, or there are too many amino acids, the molecules will enter further catabolic pathways to be broken down into carbon skeletons. These small molecules can be combined in gluconeogenesis to create new glucose, which the cells can use as energy or store in large molecules. During starvation, cellular proteins can go through the catabolism to allow an organism to survive on its own tissues until more food is found. In this way, organisms can live with only small amounts of water for extremely long times. This makes them much more resilient to changing environmental conditions.


Examples of Negative Feedback

Regulating Blood Sugar

Every time you eat, a negative feedback mechanism controls the level of sugar in your blood. The main sugar found in your blood is glucose. After you eat something, your body absorbs the glucose from your bloodstream and deposits it into your blood. This increases the concentration of glucose and stimulates you pancreas to release a chemical called insulin. Insulin is a cellular signaling molecule which tells muscle and liver cells to uptake glucose. Liver cells store the excess glucose as glycogen, a chain of glucoses used as a storage product. Muscle cells can store the glucose or use it to make ATP and contract. As this process happens, glucose concentrations are depleted in the blood. Glucose was the main signal for the pancreas to produce insulin. Without it, the pancreas stops producing insulin and the cells stop taking up glucose. Thus, glucose levels are maintained in a specific range and the rest of the body has access to glucose consistently. The negative feedback mechanism in this system is seen specifically in how high glucose levels lead to the pathway turning on, which leads to a product meant to lower the glucose level. When glucose becomes too low, the pathway shuts off.

Temperature Regulation

All endotherms regulate their temperature. Endotherms are animals which regulate their bodies at a different temperature than the environment. You can think of mammals and birds as the most common endotherms. Most of the pathways responsible for temperature regulation are controlled by negative feedback. As the temperature rises, enzymes and pathways in the body are “turned-on”, and control various behaviors like sweating, panting and seeking shade. As the animal does these things, the temperature of their body starts to decrease. The activity of these pathways, which is driven by the heat, also starts to decrease. Eventually, a temperature is reached at which the pathway shuts off. Other pathways are present for temperatures that are too cold, and are also shut off once the body reaches the optimal temperature. These pathways can be shivering, seeking shelter, or burning fat. All these activities heat the body back up and are shut off by the end product of their reactions, heat.

Filling a Toilet Tank

Many students tend to struggle with abstract biological examples of negative feedback. Have no fear! A simple and common house-hold item uses negative feedback every day. In the tank on the back of your toilet is a ball or float, which rests at water level. When you empty the tank, the water level drops. The pressure from the float that was holding the valve shut releases, and new water flows into the tank. The valve controlled by the float is like an enzyme that monitors the level of the product it creates. As more water (product) fills the tank, the float slowly decreases the amount of water being let in through the valve. The valve is analogous to an enzyme which is regulated by feedback from a product it helps create or let into a cell.

1. Which of the following represents negative feedback?
A. Blood platelets release chemicals that attract more blood platelets when then fill a wound
B. One bird fleeing a predator spurs three birds, which in turn scares the whole flock
C. In producing an amino acid, the enzyme a cell uses is inhibited after the amino acid reaches a specific concentration

3. You are reaching into a hot stove to grab your dinner. Your finger slips off the hot pad, and touches the scalding hot dish in the oven. A signal is sent to your brain, which tells your arm to contract. When your finger stops burning, your arm can relax. What does this scenario represent?
A. Negative Feedback
B. Positive Feedback
C. Fight or Flight response


Niwa Lab

The Niwa laboratory focuses on understanding how the endoplasmic reticulum (ER), the gateway to the secretory pathway and source of most lipids and one third of all cellular proteins, regulates these functional demands in response to distinct environmental, developmental, or disease cues. This is achieved by studying a stress signaling pathway called the Unfolded Protein Response (UPR). (1) We study how mis-regulation of the UPR leads to human diseases, ranging from asthma to cancer using molecular, biochemical and pharmacological high-throughput screening approaches. (2) Our lab also discovered a cell cycle checkpoint in yeast that ensures that all dividing cells receive both functionally correct and spatially sufficient ER during each cell cycle. This was one of the first cell cycle checkpoints for regulating the inheritance of cytoplasmic components like the ER and it is now known as the ER stress surveillance (ERSU) checkpoint. In yeast, ERSU halts ER inheritance, leading to a block of cell division until the ER can be repaired. Using cell biological and molecular approaches, we address our pioneering work for uncovering how the ERSU checkpoint is initiated in response to ER stress and communicates with cell cycle progression. (3) Recently, the lab made seminal discoveries in both yeast and mammals showing that ER stress induces specific sphingolipids and these in turn act as key inducers for the ER cell cycle checkpoint. (4) Furthermore, our lab is expanding into a new and exciting area in cell biology: how the ER communicates architecturally and functionally with the nucleus, through the use of CRISPR/Cas9-based genetics, microfluidics, and state-of the-art live cell imaging. (5) Failure of the ER to meet such demands is an underlying cause of many human diseases, including cancers such as multiple myeloma and pancreatic cancer, as well as diseases ranging from Alzheimer’s and Parkinson’s to cystic fibrosis, type 2 diabetes, and obesity. Thus, understanding how the ER is regulated and how it meets the challenges presented by constantly fluctuating developmental and environmental changes has great biological and medical significance.


What are these pathways called in Biology? - Biology

A. Two Pathways
1. Two electron pathways operate in the thylakoid membrane: the noncyclic pathway and the cyclic pathway.
2. Both pathways produce ATP but only the noncyclic pathway also produces NADPH.
3. ATP production during photosynthesis is sometimes called photophosphorylation therefore these pathways are also known as cyclic and noncyclic photophosphorylation.

B. Noncyclic Electron Pathway (*SPLITS WATER, PRODUCES NADPH & ATP)

1. This pathway occurs in the thylakoid membranes and requires participation of two light-gathering units: photosystem I (PS I) and photosystem II (PS II).
2. A photosystem is a photosynthetic unit comprised of a pigment complex and electron acceptor solar energy is absorbed and high-energy electrons are generated.
3. Each photosystem has a pigment complex composed of green chlorophyll a and chlorophyll b molecules and orange and yellow accessory pigments (e.g., carotenoid pigments).
4. Absorbed energy is passed from one pigment molecule to another until concentrated in reaction-center chlorophyll a.
5. Electrons in reaction-center chlorophyll a become excited they escape to electron-acceptor molecule.
6. The noncyclic pathway begins with PSII electrons move from H2O through PS II to PS I and then on to NADP+.
7. The PS II pigment complex absorbs solar energy high-energy electrons (e-) leave the reaction-center chlorophyll a molecule.
8. PS II takes replacement electrons from H2O, which splits, releasing O2 and H+ ions:
9. Oxygen is released as oxygen gas (O2).
10. The H+ ions temporarily stay within the thylakoid space and contribute to a H+ ion gradient.
11. As H+ flow down electrochemical gradient through ATP synthase complexes, chemiosmosis occurs.
12. Low-energy electrons leaving the electron transport system enter PS I.
13. When the PS I pigment complex absorbs solar energy, high-energy electrons leave reaction-center chlorophyll a and are captured by an electron acceptor.
14. The electron acceptor passes them on to NADP+.
15. NADP+ takes on an H+ to become NADPH: NADP+ + 2 e- + H+  NADPH.
16. NADPH and ATP produced by noncyclic flow electrons in thylakoid membrane are used by enzymes in stroma during light-independent reactions.

C. Cyclic Electron Pathway
1. The cyclic electron pathway begins when the PS I antenna complex absorbs solar energy.
2. High-energy electrons leave PS I reaction-center chlorophyll a molecule.
3. Before they return, the electrons enter and travel down an electron transport system.

a. Electrons pass from a higher to a lower energy level.
b. Energy released is stored in form of a hydrogen (H+) gradient.
c. When hydrogen ions flow down their electrochemical gradient through ATP synthase complexes, ATP production occurs.
d. Because the electrons return to PSI rather than move on to NADP+, this is why it is called cyclic and also why no NADPH is produced.

D. ATP Production (chemiosmosis)
1. The thylakoid space acts as a reservoir for H+ ions each time H2O is split, two H+ remain.
2. Electrons move carrier-to-carrier, giving up energy used to pump H+ from the stroma into the thylakoid space.
3. Flow of H+ from high to low concentration across thylakoid membrane provides energy to produce ATP from ADP + P by using an ATP synthase enzyme

**Now is a good time to look at the various animations of these processes. The trick is to VISUALIZE them*


Biology students often choose careers as research scientists or college professors, for which students must first obtain a PhD. In the private sector, a master&rsquos degree may be sufficient for a research or product-development position. Some biology majors, particularly those with research experience, find research assistant positions directly after obtaining their bachelor&rsquos degrees.

Many biology students go on to careers in medicine or some other health profession. While a major in the biological sciences is not a requirement for medical school (or other professional schools in the health sciences), it has many advantages with its exposure to the basic principles of life&rsquos processes and the theoretical underpinnings of sophisticated medical procedures.

Some students move into other science careers such as education (K&ndash12), business (e.g., pharmaceutical sales), or jobs in nature centers, parks and recreation, or government.


Fundamental Roles of Glucosamine in Brain Revealed

Using novel imaging methods for studying brain metabolism, University of Kentucky researchers have identified the reservoir for a necessary sugar in the brain. Glycogen serves as a storage depot for the sugar glucose.

The laboratories of Ramon Sun, Ph.D., assistant professor of neuroscience, Markey Cancer Center at the University of Kentucky College of Medicine, and Matthew Gentry, Ph.D., professor of molecular and cellular biochemistry and director of the Lafora Epilepsy Cure Initiative at the University of Kentucky College of Medicine discovered that glucose – the sugar used for cellular energy production – was not the only sugar contained in glycogen in the brain. Brain glycogen also contained another sugar called glucosamine.

The full study was recently published in Cell Metabolism.

Some forms of glucosamine, such as glucosamine sulfate and glucosamine hydrochloride, are common supplements used to improve joint movement.

However, within cells, glucosamine is an essential sugar needed for the complex carbohydrate chains that are attached to proteins in a process called glycosylation. These sugar chains decorate proteins and the sugar decorations are critical for the appropriate function of myriad proteins.

Discovering that glucosamine is a major component of brain glycogen provides key insight into neurological diseases caused by aberrant glycogen-like cellular aggregates called polyglucosan bodies (PGBs).

Lafora disease is a rare, inherited childhood dementia caused by PGBs and this study demonstrates that the Lafora disease PGBs sequester glucosamine, leading to numerous cellular perturbations. PGBs also accumulate in the brain as people age and in people with other forms of dementia. Thus, the discovery that glycogen is also a storage cache for glucosamine has broad implications for understanding neurological changes associated with aging.

Using biochemical approaches, the researchers determined the sugar composition of glycogen in the muscle, liver, and brain of mice. Unlike muscle glycogen, which had only 1% glucosamine, and liver glycogen, which had less than 1% glucosamine, brain glycogen contained 25% glucosamine. “The discovery that brain glycogen is comprised of 25% glucosamine was stunning,” stated Sun.

Upon making this surprising discovery, they then identified the enzymes responsible for incorporating glucosamine into glycogen and for releasing glucosamine from glycogen. Again, the discovery was unexpected as these enzymes are the same ones used to incorporate glucose into and release glucose from glycogen.

To understand the implications of their findings for Lafora disease and neurological problems arising from PGBs, the researchers used their newly developed technique called matrix-assisted laser desorption/ionization traveling-wave ion-mobility high-resolution mass spectrometry (MALDI TW IMS) to measure and visualize the amount of glycogen in different regions of the brain. They also used this technique to quantify changes in the specific patterns of the sugar decorations on proteins in multiple regions of the brain.

The team applied MALDI TW IMS to analyze the brains of healthy mice and of two different mouse models of glycogen storage diseases: a model of Lafora disease and a model of glucose storage disease (GSD) type III. Sun commented, “This new technique allows us to quantify the amount of these sugars with high accuracy while also maintaining the spatial distribution within the brain regarding where the sugars are located. It is crucial that the brain has the correct sugars in the right location within the brain.”

These studies revealed that without the ability to properly regulate brain glycogen metabolism, not only do PGBs form, which perturbs cell metabolism, but the sugar decoration of proteins is also altered. Excitingly, they could restore protein sugar decoration by injecting an antibody-enzyme fusion (VAL-0417) into the brains of Lafora disease mice to degrade the PGBs.

Discovering that glucosamine is a major component of brain glycogen provides key insight into neurological diseases caused by aberrant glycogen-like cellular aggregates called polyglucosan bodies (PGBs). Image is in the public domain

Their findings show a direct connection between abnormal glycogen storage and defective protein function in the brain. Their findings have implications for many other GSDs and congenital disorders of glycosylation, which cause severe neurological symptoms, including epilepsy and dementia.

“Multiple neurological diseases have blockades in these metabolic pathways. I’m sure these pathways are going to be important in other neuro-centric diseases as well. Brain glycogen is comprised of glucose and glucosamine and brain metabolism has to balance both in order to stay healthy,” explained Gentry.

The Gentry and Sun laboratories collaborated with several others from UK College of Medicine including Drs. Craig Vander Kooi, professor of molecular and cellular biochemistry, Charles Waechter, professor of molecular and cellular biochemistry, Lance Johnson, assistant professor of physiology, Christine Brainson, assistant professor of toxicology and cancer biology.

They also worked with researchers from Indiana University School of Medicine including Drs. Anna A. DePaoli-Roach, professor of biochemistry and molecular biology, Peter J. Roach, professor of biochemistry and molecular biology, Thomas D. Hurley, professor of biochemistry and molecular biology. Richard Taylor, professor of chemistry and biochemistry, from the University of Notre Dame, and Richard Drake, professor of cell and molecular pharmacology and experimental therapeutics from the Medical University of South Carolina, also contributed to this work.