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Where Does The Glucose That Is Released Into The Blood Ultimately End Up (2 Places)?

Exocytosis

Exocytosis

Exocytosis is the cellular process in which intracellular vesicles in the cytoplasm fuse with the plasma membrane and release or "secrete" their contents into the extracellular space. Exocytosis can be constitutive (occurring all the time) or regulated. Constitutive exocytosis is important in transporting proteins like receptors that function in the plasma membrane. Regulated exocytosis is triggered when a cell receives a signal from the outside. Many of the products that cells secrete function specifically for the tissue type in which the cells reside or are transmitted to more distant parts of the body. Most of these products are proteins that have gone through rigorous quality control and modification processes in the endoplasmic reticulum and Golgi membranes. It is in the trans -Golgi network, the "downstream" end of the Golgi apparatus, where cellular products are sorted and accumulate in exocytic vesicles. Mechanisms The mechanisms controlling regulated exocytosis were largely discovered in the 1990s. Contrary to early ideas, membranes normally do not fuse together spontaneously. This is due to the negative charges associated with the phospholipids that make up the lipid bilayer of the membranes of vesicles and organelles . Membrane fusion requires energy and the interaction of special "adaptor" molecules present on both the vesicle and plasma membrane. The adapter molecules are highly selective and only allow vesicles to fuse with membranes of particular organelles, thus preventing harm to the cell. Once the appropriate adapter molecules bind to each other (docking), energy stored and released by ATP forms a fusion pore between the vesicle membranes and plasma membrane. The contents of the vesicle are released to the exterior of the cell (or the interior of an or Continue reading >>

Review Brain Energy Metabolism: Focus On Astrocyte-neuron Metabolic Cooperation

Review Brain Energy Metabolism: Focus On Astrocyte-neuron Metabolic Cooperation

Main Text Introduction Glucose is the obligatory energy substrate of the adult brain. Nevertheless, under particular circumstances the brain has the capacity to use other blood-derived energy substrates, such as ketone bodies during development and starvation (Nehlig, 2004; Magistretti, 2008) or lactate during periods of intense physical activity (van Hall et al., 2009). Glucose enters cells trough specific glucose transporters (GLUTs) and is phosphorylated by hexokinase (HK) to produce glucose-6-phosphate. As in other organs, glucose 6-phosphate can be processed via different metabolic pathways (Figure 1A), the main ones being (1) glycolysis (leading to lactate production or mitochondrial metabolism), (2) the pentose phosphate pathway (PPP), and (3) glycogenesis (in astrocytes only, see below). Overall, glucose is almost entirely oxidized to CO2 and water in the brain (Clarke and Sokoloff, 1999). Nevertheless, as evidenced by the different metabolic routes that glucose can follow, each individual brain cell does not necessarily metabolize glucose to CO2 and water. Indeed, a wide range of metabolic intermediates formed from glucose in the brain can subsequently be oxidized for energy production (e.g., lactate, pyruvate, glutamate, or acetate) (Zielke et al., 2009). Figure 1. Brain Glucose Utilization (A) Schematic representation of glucose metabolism. Glucose enters cells trough glucose transporters (GLUTs) and is phosphorylated by HK to produce glucose-6-phosphate (glucose-6P). Glucose-6P can be processed into three main metabolic pathways. First, it can be metabolized through glycolysis (i), giving rise to two molecules of pyruvate and producing ATP and NADH. Pyruvate can then enter mitochondria, where it is metabolized through the tricarboxylic acid (T Continue reading >>

Targeting Hepatic Glucose Metabolism In The Treatment Of Type 2 Diabetes

Targeting Hepatic Glucose Metabolism In The Treatment Of Type 2 Diabetes

Type 2 diabetes mellitus is characterized by the dysregulation of glucose homeostasis, resulting in hyperglycaemia. Although current diabetes treatments have exhibited some success in lowering blood glucose levels, their effect is not always sustained and their use may be associated with undesirable side effects, such as hypoglycaemia. Novel antidiabetic drugs, which may be used in combination with existing therapies, are therefore needed. The potential of specifically targeting the liver to normalize blood glucose levels has not been fully exploited. Here, we review the molecular mechanisms controlling hepatic gluconeogenesis and glycogen storage, and assess the prospect of therapeutically targeting associated pathways to treat type 2 diabetes. Additional access options: Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States, 2014 (US Department of Health and Human Services, 2014). Foretz, M., Guigas, B., Bertrand, L., Pollak, M. & Viollet, B. Metformin: from mechanisms of action to therapies. Cell. Metab. 20, 953–966 (2014). This work reviews the complexities surrounding the mechanism of action of metformin, the most widely used antidiabetic drug. Sharma, R. et al. Comparison of the circulating metabolite profile of PF-04991532, a hepatoselective glucokinase activator, across preclinical species and humans: potential implications in metabolites in safety testing assessment. Drug Metab. Dispos. 43, 190–198 (2015). Lloyd, D. J. et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature 504, 437–440 (2013). The authors identify two small-molecule inhibitors of the glucokinase–GKRP interaction, and their ability to lower blood glucose levels in Continue reading >>

Cell Signalling

Cell Signalling

4 Glucose metabolism: an example of integration of signalling pathways 4.1 Glucose metabolism We are now in a position to draw together the major concepts and components of signalling, and show how they operate in one well-understood system, namely the regulation of the storage or release of glucose in the human body. From this, you will be able to recognize archetypal pathways represented in specific examples, you will be able to appreciate how the same basic pathways can be stimulated by different hormones in different tissues, and you will see how opposing hormones activate separate pathways that affect the same targets but in opposite ways. Following a meal, insulin is released into the bloodstream by pancreatic β cells. The overall systemic effects of insulin are to increase uptake of blood glucose into cells, and to promote its storage as glycogen in muscle and liver cells. (Note that glycogen is a polysaccharide consisting of repeated units of glucose used for shortterm energy storage by animal cells.) A rise in the concentration of blood glucose, such as that following the consumption of food, stimulates insulin production, which signals through the insulin RTK. The insulin RTK phosphorylates various substrate proteins, which link to several key signalling pathways such as the Ras–MAP kinase pathway. There are, however, two major pathways that control glycogen synthesis and breakdown in animal cells (Figure 47). Figure 47 The control of glycogen synthesis by insulin. Several proteins bind, and are phosphorylated by, the activated insulin receptor. Cbl activates a pathway that is implicated in the translocation of the glucose transporter GLUT4 to the membrane, allowing glucose transport into the cell. Meanwhile, IRS-1 serves as a docking protein for PI 3-kinas Continue reading >>

Glycogen Metabolism

Glycogen Metabolism

Introduction Glycogen Breakdown: Glycogenolysis Glycogen Synthesis: Glycogenesis Regulation of Glycogen Homeostasis Regulation of Glycogen Catabolism Regulation of Glycogen Synthesis Clinical Significances of Glycogen Metabolism Table of Glycogen Storage Diseases Return to The Medical Biochemistry Page © 1996–2017 themedicalbiochemistrypage.org, LLC | info @ themedicalbiochemistrypage.org Introduction Stores of readily available glucose to supply the tissues with an oxidizable energy source are found principally in the liver, as glycogen. Glycogen is a polymer of glucose residues linked by α-(1,4)- and α-(1,6)-glycosidic bonds. A second major source of stored glucose is the glycogen of skeletal muscle. However, muscle glycogen is not generally available to other tissues, because muscle lacks the enzyme glucose-6-phosphatase. Glycogen Structure. Section of a glycogen polymer depicting glucose monomers as colored balls. The blue balls represent glucose linked by α1,4 glycosidic bonds. The red balls represent glucose at branch points where there are both α1,4 and α1,6 glycosidic bonds. The orange balls represent the reducing ends of the polymeric chains of α1,4-linked glucoses. The area in the box is expanded to show the actual structure of the glucose monomers in both α-1,4- and α-1,6 glycosidic linkages. The major site of daily glucose consumption (75%) is the brain via aerobic pathways. Most of the remainder of is utilized by erythrocytes, skeletal muscle, and heart muscle. The body obtains glucose either directly from the diet or from amino acids and lactate via gluconeogenesis. Glucose obtained from these two primary sources either remains soluble in the body fluids or is stored in a polymeric form, glycogen. Glycogen is considered the principal storage for Continue reading >>

Respiration

Respiration

CONCEPT Respiration is much more than just breathing; in fact, the term refers to two separate processes, only one of which is the intake and outflow of breath. At least cellular respiration, the process by which organisms convert food into chemical energy, requires oxygen; on the other hand, some forms of respiration are anaerobic, meaning that they require no oxygen. Such is the case, for instance, with some bacteria, such as those that convert ethyl alcohol to vinegar. Likewise, an anaerobic process can take place in human muscle tissue, producing lactic acid—something so painful that it feels as though vinegar itself were being poured on an open sore. HOW IT WORKS FORMS OF RESPIRATION Respiration can be defined as the process by which an organism takes in oxygen and releases carbon dioxide, one in which the circulating medium of the organism (e.g., the blood) comes into contact with air or dissolved gases. Either way, this means more or less the same thing as breathing. In some cases, this meaning of the term is extended to the transfer of oxygen from the lungs to the bloodstream and, eventually, into cells or the release of carbon dioxide from cells into the bloodstream and thence to the lungs, from whence it is expelled to the environment. Sometimes a distinction is made between external respiration, or an exchange of gases with the external environment, and internal respiration, an exchange of gases between the body's cells and the blood, in which the blood itself "bathes" the cells with oxygen and receives carbon dioxide to transfer to the environment. This is just one meaning—albeit a more familiar one—of the word respiration. Respiration also can mean cellular respiration, a series of chemical reactions within cells whereby food is "burned" in the presen Continue reading >>

How Insulin Really Works: It Causes Fat Storage…but Doesn’t Make You Fat

How Insulin Really Works: It Causes Fat Storage…but Doesn’t Make You Fat

Many people believe that insulin is to blame for the obesity epidemic. When you understand how it actually works, you’ll know why this is a lie. Insulin has been taking quite a beating these days. If we’re to listen to some “experts,” it’s an evil hormone whose sole goal is making us fat, type 2 diabetics. Furthermore, we’re told that carbohydrates also are in on the conspiracy. By eating carbs, we open the insulin floodgates and wreak havoc in our bodies. How true are these claims, though? Does it really make sense that our bodies would come with an insidious mechanism to punish carbohydrate intake? Let’s find out. What is Insulin, Anyway? Insulin is a hormone, which means it’s a substance the body produces to affect the functions of organs or tissues, and it’s made and released into the blood by the pancreas. Insulin’s job is a very important one: when you eat food, it’s broken down into basic nutrients (protein breaks down into amino acids; dietary fats into fatty acids; and carbohydrates into glucose), which make their way into the bloodstream. These nutrients must then be moved from the blood into muscle and fat cells for use or storage, and that’s where insulin comes into play: it helps shuttle the nutrients into cells by “telling” the cells to open up and absorb them. So, whenever you eat food, your pancreas releases insulin into the blood. As the nutrients are slowly absorbed into cells, insulin levels drop, until finally all the nutrients are absorbed, and insulin levels then remain steady at a low, “baseline” level. This cycle occurs every time you eat food: amino acids, fatty acids, and/or glucose find their way into your blood, and they’re joined by additional insulin, which ushers them into cells. Once the job is done, insu Continue reading >>

Glycogen Breakdown

Glycogen Breakdown

Glycogen Structure Glycogen is a polymer of glucose (up to 120,000 glucose residues) and is a primary carbohydrate storage form in animals. The polymer is composed of units of glucose linked alpha(1-4) with branches occurring alpha(1-6) approximately every 8-12 residues. The end of the molecule containing a free carbon number one on glucose is called a reducing end. The other ends are all called non-reducing ends. Related polymers in plants include starch (alpha(1-4) polymers only) and amylopectin (alpha (1-6) branches every 24-30 residues). Glycogen provides an additional source of glucose besides that produced via gluconeogenesis. Because glycogen contains so many glucoses, it acts like a battery backup for the body, providing a quick source of glucose when needed and providing a place to store excess glucose when glucose concentrations in the blood rise. The branching of glycogen is an important feature of the molecule metabolically as well. Since glycogen is broken down from the "ends" of the molecule, more branches translate to more ends, and more glucose that can be released at once. Liver and skeletal muscle are primary sites in the body where glycogen is found. Overview The primary advantages of storage carbohydrates in animals are that 1) energy is not released from fat (other major energy storage form in animals) as fast as from glycogen; 2) glycolysis provides a mechanism of anaerobic metabolism (important in muscle cells that cannot get oxygen as fast as needed); and 3) glycogen provides a means of maintaining glucose levels that cannot be provided by fat. Breakdown of glycogen involves 1) release of glucose-1-phosphate (G1P), 2) rearranging the remaining glycogen (as necessary) to permit continued breakdown, and 3) conversion of G1P to G6P for further metab Continue reading >>

Glycolysis

Glycolysis

Glucose G6P F6P F1,6BP GADP DHAP 1,3BPG 3PG 2PG PEP Pyruvate HK PGI PFK ALDO TPI GAPDH PGK PGM ENO PK Glycolysis The metabolic pathway of glycolysis converts glucose to pyruvate by via a series of intermediate metabolites. Each chemical modification (red box) is performed by a different enzyme. Steps 1 and 3 consume ATP (blue) and steps 7 and 10 produce ATP (yellow). Since steps 6-10 occur twice per glucose molecule, this leads to a net production of ATP. Summary of aerobic respiration Glycolysis (from glycose, an older term[1] for glucose + -lysis degradation) is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).[2][3] Glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis. For example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful. For example, the intermediate dihydroxyacetone phosphate (DHAP) is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen independent metabolic pathway, meaning that it does not use molecular oxygen (i.e. atmospheric oxygen) for any of its reactions. However the products of glycolysis (pyruvate and NADH + H+) are sometimes metabolized using atmospheric oxygen.[4] When molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as aerobic, whereas if no oxygen is used the process is said to be anaerobic.[5] Thus, glycolysis occurs, with variations, in nearly all organisms, both aerobic and a Continue reading >>

Metabolism, Insulin And Other Hormones

Metabolism, Insulin And Other Hormones

Metabolism literally means transformation but has become a general term that encompasses all chemical processes that occur in the living body; processes that are the essence of life. These include processes that build up tissues (anabolism) and that make tissues function, which generally cost energy, and processes that degrade tissues (catabolism), which generally produce energy. However, a full description of everything that goes on in the body is beyond our scope: in this section we will focus on the normal physiology of processes that are related to the handling of nutrients (sugars, proteins and fat) and their regulation, with particular attention for the processes that become disturbed in diabetes. These processes of glucose metabolism, lipid metabolism, ketone body metabolism, protein metabolism and amino acid metabolism are controlled by a set of glucoregulatory hormones such as insulin, glucagon , amylin, the incretins (GLP-1, glucose-dependent insulinotropic peptide (GIP)), several adipokines (leptin, adiponectin, acylation stimulating protein and resistin), epinephrine, cortisol, and growth hormone. Of these, insulin and amylin are derived from the β-cells of the pancreas, glucagon from the α-cells of the pancreas, GLP-1 and GIP from the L-cells of the intestine and the adipokines from adipose tissue[1][2][3]. What is Metabolism? Metabolism refers to the pathways of biochemical processes (metabolic pathways) that occur in all living organisms to maintain life[4][5][6]. These biochemical processes allow us to grow, reproduce, repair damage, and respond to our environment. Throughout its lifetime the body undergoes cycles of building and degradation, taking up fuel and building blocks in the form of food, ultimately to lose them as water, carbon dioxide, urea Continue reading >>

Section 16.1oxidation Of Glucose And Fatty Acids To Co2

Section 16.1oxidation Of Glucose And Fatty Acids To Co2

The complete aerobic oxidation of glucose is coupled to the synthesis of as many as 36 molecules of ATP: Glycolysis, the initial stage of glucose metabolism, takes place in the cytosol and does not involve molecular O. It produces a small amount of ATP and the three-carbon compound pyruvate. In aerobic cells, pyruvate formed in glycolysis is transported into the mitochondria, where it is oxidized by O to CO. Via chemiosmotic coupling, the oxidation of pyruvate in the mitochondria generates the bulk of the ATP produced during the conversion of glucose to CO. In this section, we discuss the biochemical pathways that oxidize glucose and fatty acids to CO and HO; the fate of the released electrons is described in the next section. Go to: Cytosolic Enzymes Convert Glucose to Pyruvate A set of 10 enzymes catalyze the reactions, constituting the glycolytic pathway, that degrade one molecule of glucose to two molecules of pyruvate (Figure 16-3). All the metabolic intermediates between glucose and pyruvate are watersoluble phosphorylated compounds. Four molecules of ATP are formed from ADP in glycolysis (reactions 6 and 9). However, two ATP molecules are consumed during earlier steps of this pathway: the first by the addition of a phosphate residue to glucose in the reaction catalyzed by hexokinase (reaction 1), and the second by the addition of a second phosphate to fructose 6-phosphate in the reaction catalyzed by phosphofructokinase-1 (reaction 3). Thus there is a net gain of two ATP molecules. The balanced chemical equation for the conversion of glucose to pyruvate shows that four hydrogen atoms (four protons and four electrons) are also formed: (For convenience, we show pyruvate in its un-ionized form, pyruvic acid, although at physiological pH it would be largely dissociat Continue reading >>

65 10.3 Muscle Fiber Contraction And Relaxation

65 10.3 Muscle Fiber Contraction And Relaxation

Learning Objectives By the end of this section, you will be able to: Describe the components involved in a muscle contraction Explain how muscles contract and relax Describe the sliding filament model of muscle contraction The sequence of events that result in the contraction of an individual muscle fiber begins with a signal—the neurotransmitter, ACh—from the motor neuron innervating that fiber. The local membrane of the fiber will depolarize as positively charged sodium ions (Na+) enter, triggering an action potential that spreads to the rest of the membrane will depolarize, including the T-tubules. This triggers the release of calcium ions (Ca++) from storage in the sarcoplasmic reticulum (SR). The Ca++ then initiates contraction, which is sustained by ATP (Figure 1). As long as Ca++ ions remain in the sarcoplasm to bind to troponin, which keeps the actin-binding sites “unshielded,” and as long as ATP is available to drive the cross-bridge cycling and the pulling of actin strands by myosin, the muscle fiber will continue to shorten to an anatomical limit. Muscle contraction usually stops when signaling from the motor neuron ends, which repolarizes the sarcolemma and T-tubules, and closes the voltage-gated calcium channels in the SR. Ca++ ions are then pumped back into the SR, which causes the tropomyosin to reshield (or re-cover) the binding sites on the actin strands. A muscle also can stop contracting when it runs out of ATP and becomes fatigued (Figure 2). Figure 2. Relaxation of a Muscle Fiber. Ca++ ions are pumped back into the SR, which causes the tropomyosin to reshield the binding sites on the actin strands. A muscle may also stop contracting when it runs out of ATP and becomes fatigued. The release of calcium ions initiates muscle contractions. Watch Continue reading >>

Glycolysis

Glycolysis

Suppose that we gave one molecule of glucose to you and one molecule of glucose to Lactobacillus acidophilus—the friendly bacterium that turns milk into yogurt. What would you and the bacterium do with your respective glucose molecules? Glycolysis is a series of reactions that and extract energy from glucose by splitting it into two three-carbon molecules called pyruvates. Glycolysis is an ancient metabolic pathway, meaning that it evolved long ago, and it is found in the great majority of organisms alive today​. In organisms that perform cellular respiration, glycolysis is the first stage of this process. However, glycolysis doesn’t require oxygen, and many anaerobic organisms—organisms that do not use oxygen—also have this pathway. Glycolysis has ten steps, and depending on your interests—and the classes you’re taking—you may want to know the details of all of them. However, you may also be looking for a greatest hits version of glycolysis, something that highlights the key steps and principles without tracing the fate of every single atom. Let’s start with a simplified version of the pathway that does just that. Glycolysis takes place in the cytosol of a cell, and it can be broken down into two main phases: the energy-requiring phase, above the dotted line in the image below, and the energy-releasing phase, below the dotted line. Energy investment phase. Glucose is first converted to fructose-1,6-bisphosphate in a series of steps that use up two ATP. Then, unstable fructose-1,6-bisphosphate splits in two, forming two three-carbon molecules called DHAP and glyceraldehyde-3-phosphae. Glyceraldehyde-3-phosphate can continue with the next steps of the pathway, and DHAP can be readily converted into glyceraldehyde-3-phosphate. Energy payoff phase. In a s Continue reading >>

Feedback Loops: Insulin And Glucagon

Feedback Loops: Insulin And Glucagon

Name: ________________________________________ The control of blood sugar (glucose) by insulin is a good example of a negative feedback mechanism. When blood sugar rises, receptors in the body sense a change. In turn, the control center (pancreas) secretes insulin into the blood effectively lowering blood sugar levels. Once blood sugar levels reach homeostasis, the pancreas stops releasing insulin. Examine the graphic below to understand how this feedback loop works. 1. The image shows two different types of stimuli (1 and 2), but doesn't explain what the stimuli is that causes blood sugar to raise or lower. Based on clues in the graphic, what are the two stimuli? 2. What happens when your blood sugar rises? 3. What is the effect of glucagon? What cells release glucagon? 4. What is the effect of insulin? What cells release insulin? 5. What is the normal level of glucose in the blood? Why is this called a "set point." 6. What would you expect to happen if your blood sugar was 120 mg / 100 mL ? Be specific. 7. A person with diabetes cannot regulate their blood sugar, mainly because the pancreas does not release enough insulin. To treat the disease, a person must monitor their blood sugar, if their blood sugar is high, they must take an injection of insulin. How do you think they would need to treat low blood sugar? 8. In a single sentence, explain the relationship between the pancreas and homeostasis. 9. Where does the glucose that is released into the blood ultimately end up (2 places)? 10. Explain how the thermostat in your house uses a negative feedback system to maintain your home's temperature. Continue reading >>

Anatomy And Function Of The Liver

Anatomy And Function Of The Liver

Anatomy of the liver The liver is located in the upper right-hand portion of the abdominal cavity, beneath the diaphragm and on top of the stomach, right kidney, and intestines. The liver, a dark reddish-brown organ, has multiple functions. There are two distinct sources that supply blood to the liver: Oxygenated blood flows in from the hepatic artery. Nutrient-rich blood flows in from the hepatic portal vein. The liver consists of two main lobes, both of which are made up of 8 segments. The segments are made up of a thousand lobules. The lobules are connected to small ducts that connect with larger ducts to ultimately form the common hepatic duct. The common hepatic duct transports bile produced by the liver cells to the gallbladder and duodenum (the first part of the small intestine). What are the functions of the liver? The liver regulates most chemical levels in the blood and excretes a product called bile. Bile helps to break down fats, preparing them for further digestion and absorption. All of the blood leaving the stomach and intestines passes through the liver. The liver processes this blood and breaks down, balances, and creates nutrients for the body to use. It also metabolized drugs in the blood into forms that are easier for the body to use. Many vital functions have been identified with the liver. Some of the more well-known functions include the following: Production of bile, which helps carry away waste and break down fats in the small intestine during digestion Production of certain proteins for blood plasma Production of cholesterol and special proteins to help carry fats through the body Store and release glucose as needed Processing of hemoglobin for use of its iron content (the liver stores iron) Conversion of harmful ammonia to urea (urea is one of Continue reading >>

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