Sugar metabolism -
This method of control is called reciprocal regulation see above. Reciprocal regulation is a coordinated means of simultaneously controlling metabolic pathways that do opposite things. Reciprocal allosteric effects For example, in glycolysis, the enzyme known as phosphofructokinase PFK-1 is allosterically activated by AMP and a molecule known as F2,6BP Figure 6.
The corresponding enzyme from gluconeogenesis catalyzing a reversal of the glycolysis reaction is known as F1,6BPase. F1,6BPase is inhibited by both AMP and F2,6BP. In glycogen metabolism, the enzymes phosphorylase kinase and glycogen phosphorylase catalyze reactions important for the breakdown of glycogen.
The enzyme glycogen synthase catalyzes the synthesis of glyco- Directional velocity Inverts with reciprocity If glycolysis is flowing Glucose synthesis awaits But when the latter is a-going Sugar breakdown then abates Figure 6.
Each of these enzymes is, at least partly, regulated by attachment and removal of phosphate. Phosphorylation of phosphorylase kinase and glycogen phosphorylase has the effect of making them more active, whereas phosphorylation of glycogen synthase makes it less active.
Conversely, dephosphorylation has the reverse effects on these enzymes - phosphorylase kinase and glycogen phosphorylase become less active and glycogen synthase becomes more active.
The advantage of reciprocal regulation schemes is that they are very efficient. Further, its simplicity ensures that when one pathway is turned on, the other is turned off.
A simple futile cycle is shown on Figure 6. If unregulated, the cyclic pathway in the figure shown in black will make ATP in creating pyruvate from PEP and will use ATP to make oxaloacetate from pyruvate.
It will also use GTP to make PEP from oxaloacetate. Thus, each turn of the cycle will make one ATP, use one ATP and use one GTP for a net loss of energy. The process will start with pyruvate and end with pyruvate, so there is no net production of molecules.
see HERE for one physiological use of a futile cycle. Besides reciprocal regulation, other mechanisms help control gluconeogenesis. First, PEPCK is controlled largely at the level of synthesis. Overexpression of PEPCK stimulated by glucagon, glucocorticoid hormones, and cAMP and inhibited by insulin produces symptoms of diabetes.
Pyruvate carboxylase is sequestered in the mitochondrion one means of regulation Figure 6. Acetyl-CoA concentrations increase as the citric acid cycle activity decreases. Glucose phosphatase is present in low concentrations in many tissues, but is found most abundantly and importantly in the major gluconeogenic organs — the liver and kidney cortex.
Control of glycolysis and gluconeogenesis is unusual for metabolic pathways, in that regulation occurs at multiple points. For glycolysis, this involves three enzymes:. Regulation of hexokinase is the simplest of these. The enzyme is unusual in being inhibited by its product, glucosephosphate.
This ensures when glycolysis is slowing down hexokinase is also slowing down to reduce feeding the pathway. It might also seem odd that pyruvate kinase, the last enzyme in the pathway, is regulated Figure 6.
Pyruvate kinase catalyzes the most energetically rich reaction of glycolysis. In other words, it takes two enzymes, two reactions, and two triphosphates ATP and GTP to go from one pyruvate back to one PEP in gluconeogenesis.
When cells are needing to make glu- igure 6. Consequently, pyruvate kinase must be inhibited during gluconeogenesis or a futile cycle will occur and no glucose will be made. Another interesting control mechanism called feedforward activation involves pyruvate kinase.
Pyruvate kinase is activated allosterically by the glycolysis intermediate, F1,6BP. This molecule is a product of the PFK-1 reaction and a substrate for the aldolase reaction. When this happens, some of the excess F1,6BP binds to pyruvate kinase, which activates and jump- Figure 6.
As a consequence, the concentrations of GLYAL3P and DHAP fall, helping to pull the aldolase reaction forward.
PFK-1 has a complex regulation scheme. First, it is reciprocally regulated relative to F1,6BPase by three molecules. F2,6BP activates PFK-1 and inhibits F1,6BPase. PFK-1 is also allosterically activated by AMP, whereas F1,6BPase is inhibited.
On the other hand, citrate inhibits PFK-1, but activates F1,6BPase. PFK-1 is also inhibited by ATP and is exquisitely sensitive to proton concentration, easily losing activity when the pH drops only slightly.
The root of this conundrum is that PFK-1 has two ATP binding sites - one at an allosteric site that binds ATP relatively inefficiently and one that the active site that binds ATP with high affinity. Thus, only when ATP concentration is high is binding at the allosteric site favored and only then can ATP turn off the enzyme.
Regulation of PFK-1 by F2,6BP is simple at the PFK-1 level, but more complicated at the level of synthesis of F2,6BP. Instead, it is made from fructosephosphate and ATP by the enzyme known as phosphofructokinase-2 PFK- 2 - Figure 6. With respect to energy, the liver and muscles act complementarily.
The liver is the major or- Figure 6. Muscles are major users of glucose to make ATP. Actively exercising muscles use oxygen faster than the blood can deliver it.
As a consequence, the muscles go anaerobic and produce lactate. This lactate is of no use to muscle cells, so they dump it into the blood. Lactate travels in the blood to the liver, which takes it up and reoxidizes it back to pyruvate, catalyzed by the enzyme lactate dehydrogenase Figure 6.
Pyruvate in the liver is then converted to glucose by gluconeogenesis. The glucose thus made by the liver is dumped into the bloodstream where it is taken up by muscles and used for energy, completing the important intercellular pathway known as the Cori cycle. The glucose alanine cycle also known as the Cahill Cycle , has been described as the amine equivalent of the Cori cycle Figure 6.
The Cori cycle, of course, exports lac- Figure 6. The liver, in turn, converts lactate to glucose, which it ships back to the muscles via the bloodstream. The Cori Cycle is an essential source of glucose energy for muscles during periods of exercise when oxygen is used faster than it can be delivered.
In the glucose-alanine cycle, cells are generating toxic amines and must export them. This is accomplished by transaminating pyruvate the product of glycolysis to produce the amino acid alanine.
The glucose-alanine process requires the enzyme alanine aminotransferase, which is found in muscles, liver, and intestines. Alanine is exported in the process to the blood and picked up by the liver, which deaminates it to release the amine for synthesis of urea and excretion.
The pyruvate left over after the transamination is a substrate for gluconeogenesis. Glucose produced in the liver is then exported to the blood for use by cells, thus completing the cycle. Sugars are metabolized rapidly in the body and that is one of the primary reasons they are used.
Managing levels of glucose in the body is very important - too much leads to complications related to diabetes and too little gives rise to hypoglycemia low blood sugar. Sugars in the body are maintained by three processes - 1 diet; 2 synthesis gluconeogenesis ; and 3 storage. The storage forms of sugars are, of course, the polysaccharides and their metabolism is our next topic of discussion.
The energy needs of a plant are much less dynamic than those of animals. Muscular contraction, nervous systems, and information processing in the brain require large amounts of quick energy. Because of this, the polysaccharides stored in plants are somewhat less complicated than those of animals.
Plants store glucose for energy in the form of amylose Figure 6. These structures differ in that cellulose contains glucose units solely joined by β-1,4 bonds, whereas amylose has only α-1,4 bonds and amylopectin has α-1,4 and α-1,6 bonds.
Animals store glucose primarily in liver and muscle in the form of a compound related to amylopectin known as glycogen. The structural differences between glycogen and amylopectin are solely due to the frequency of the α-1,6 branches of glucoses.
In glycogen they occur about every 10 residues instead of every , as in amylopectin Figure 6. 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. Just as in gluconeogenesis, the cell has a separate mechanism for glycogen synthesis that is distinct from glycogen breakdown.
As noted previously, this allows the cell to separately control the reactions, avoiding futile cycles, and enabling a process to occur efficiently synthesis of glycogen that would not occur if Figure 6.
Breakdown of glycogen involves 1 release of glucosephosphate G1P , 2 rearranging the remaining glycogen as necessary to permit continued breakdown, and 3 conversion of G1P to G6P for further metabolism.
G6P can be 1 used in glycolysis, 2 converted to glucose by gluconeogenesis, or 3 oxidized in the pentose phosphate pathway. Glycogen phosphorylase sometimes simply called phosphorylase catalyzes breakdown of glycogen into glucose Phosphate G1P - Figure 6.
The reaction that produces G1P from glycogen is a phosphorolysis, not a hydrolysis reaction. The distinction is that hydrolysis reactions use water to cleave bigger molecules into smaller ones, but phosphorolysis reactions use phosphate instead for the same purpose.
Note that the phosphate is just that - it does NOT come from ATP. Since ATP is not used to put phosphate on G1P, the reaction saves the cell energy. Glycogen phosphorylase will only act on nonreducing ends of a glycogen chain that are at least 5 glucoses away from a branch point. A second enzyme, Glycogen Debranching Enzyme GDE also called debranching enzyme , is therefore needed to convert α branches to α branches.
GDE acts on glycogen branches that have reached their limit of phosphorylysis with glycogen phosphorylase. GDE acts to transfer a trisaccharide from an α-1,6 branch onto an adjacent α-1,4 branch, leaving a single glucose at the 1,6 branch. Note that the enzyme also catalyzes the hydrolysis of the remaining glucose at the 1,6 branch point Figure 6.
Thus, the breakdown products from glycogen are G1P and glucose mostly G1P. Glucose can, of course, be converted to GlucosePhosphate G6P as the first step in glycolysis by either hexokinase or glucokinase.
G1P can be converted to G6P by action of an enzyme called phosphoglucomutase. This reaction is readily reversible, allowing G6P and G1P to be interconverted as the concentration of one or the other increases.
This is important, because phosphoglucomutase is needed to form G1P for glycogen synthesis. Regulation of glycogen metabolism is complex, occurring both allosterically and via hormone-receptor controlled events that result in protein phosphorylation or dephosphorylation.
In order to avoid a futile cycle of glycogen synthesis and breakdown simultaneously, cells have evolved an elaborate set of controls that ensure only one pathway is primarily active at a time. Regulation of glycogen metabolism is managed by the enzymes glycogen phosphorylase and glycogen synthase.
Its regulation is consistent with the energy needs of the cell. High energy molecules ATP, G6P, glucose al- Figure 6. Glycogen phosphorylase exists in two different covalent forms — one form with phosphate called GPa here and one form lacking phosphate GPb here.
GPb is converted to GPa by phosphorylation by an enzyme known as phosphorylase kinase. GPa and GPb can each exist in an 'R' state and a 'T' state Figure 6. For both GPa and GPb, the R state is the more active form of the enzyme.
GPa's negative allosteric effector glucose is usually not abundant in cells, so GPa does not flip into the T state often.
There is no positive allosteric effector of GPa. When glucose is absent, GPa automatically flips into the R more active state Figure 6. It is for this reason that people tend to think of GPa as being the more active covalent form of the enzyme.
GPb can convert from the GPb T state to the GPb R state by binding AMP. Unless a cell is low in energy, AMP concentration is low. Thus GPb is not converted Figure 6. This is why people think of the GPb form as less active than GPa.
The relative amounts of GPa and GPb largely govern the overall process of glycogen breakdown, since GPa tends to be active more often than GPb.
It is i. Phosphorylase kinase itself has two covalent forms — phosphorylated active and dephosphorylated inactive. It is phosphorylated by the enzyme Protein Kinase A PKA -. Another way to activate the enzyme is allosterically with calcium Figure 6.
Phosphory- Figure 6. PKA is activated by cAMP, which is, in turn, produced by adenylate cyclase after activation by a G-protein See HERE for overview. G-proteins are activated ultimately by binding of ligands to specific membrane receptors called 7-TM receptors, also known as Gprotein coupled receptors.
These are discussed in greater detail HERE. Common ligands for 7-TM receptors include epinephrine binds β- adrenergic receptor and glucagon binds glucagon receptor. Epinephrine exerts its greatest effects on muscle and glucagon works preferentially on the liver. Thus, epinephrine and glucagon can activate glycogen breakdown by stimulating synthesis of cAMP followed by the cascade of events described above.
Turning off signals is as important, if not more so, than turning them on. Glycogen is a precious resource.
If its breakdown is not controlled, a lot of energy used in its synthesis is wasted. The steps in the glycogen breakdown regulatory pathway can be reversed at every level. First, the ligand epinephrine or glucagon can leave the receptor, turning off the stimulus. Second, the G-proteins have an inherent GTPase activity.
GTP, of course, is what activates Gproteins, so a GTPase activity converts the GTP it is carrying to GDP and the G-protein becomes inactive. Thus, G-proteins turn off Figure 6.
Interfering with their ability to convert GTP to GDP can have dire consequences, including cancer in some cases. Third, cells have phosphodiesterase enzymes inhibited by caffeine for breaking down cAMP. cAMP is needed to activate PKA, so breaking it down stops PKA from activating phosphorylase kinase.
Fourth, the enzyme known as phosphoprotein phosphatase also called PP1 plays a major role. It can remove phosphates from phosphorylase kinase inactivating it and form GPa, converting it to the less likely to be active GPb.
Regulation of phosphoprotein phosphatase activity occurs at several levels. Two of these are shown in Figures 6. In Figure 6. The inhibitor PI-1 can block activity of phosphpoprotein phosphatase only if it PI-1 is phosphorylated. When PI-1 gets dephosphorylated, it no longer functions as an inhibitor, so phosphoprotein phosphatase be- Figure 6.
Now, here is the clincher - PI-1 gets phosphorylated by PKA thus, when epinephrine or glucagon binds to a cell and gets dephosphorylated when insulin binds to a cell.
Another way to regulate phosphoprotein phosphatase in the liver involves GPa directly Figure 6. In liver cells, phosphoprotein phosphatase is bound to a protein called GL. GL can also bind to GPa. As shown in the figure, if the three proteins are complexed together top of figure , then PP1 phosphoprotein phosphatase is inactive.
When glucose is present such as when the liver has made too much glucose , then the free glucose binds to the GPa and causes GPa to be released from the GL. This has the effect of activating phosphoprotein phosphatase, which begins dephosphorylating enzymes.
As shown in the figure, two such enzymes are GPa making GPb and glycogen synthase b, making glycogen synthase a. These dephosphorylations have opposite effects on the two enzymes, making GPb, which is less active and glycogen synthase a, which is much more active.
The anabolic pathway opposing glycogen breakdown is that of glycogen synthesis. Just Figure 6. Synthesis of glycogen starts with G1P, which is converted to an 'activated' intermediate, UDPglucose. This activated intermediate is what 'adds' the glucose to the growing glycogen chain in a reaction catalyzed by the enzyme known as glycogen synthase Figure 6.
Once the glucose is added to glycogen, the glycogen molecule may need to have branches inserted in it by the enzyme known as branching enzyme Figure 6. Let us first consider the steps in glycogen synthesis. G1P is reacted with UTP to form UDP-glucose in a reaction catalyzed by UDP-glucose pyrophosphorylase.
Glycogen synthase catalyzes synthesis of glycogen by joining carbon 1 of the UDP-derived glucose onto the carbon 4 of the non-reducing end of a glycogen chain, to form the familiar α 1,4 glycogen links.
Another product of the reaction is UDP. It is also worth noting, in passing, that glycogen synthase will only add glucose units from UDP-Glucose onto a preexisting glycogen chain that has at least four glucose residues.
Linkage of the first few glucose units to form the minimal "primer" needed for glycogen synthase recognition is catalyzed by a protein called glycogenin, which attaches to the first glucose and catalyzes linkage of the first eight glucoses by α 1,4 bonds.
Branching enzyme breaks α 1,4 chains and carries the broken chain to the carbon 6 and forms an α 1,6 linkage Figure 6.
The regulation of glycogen biosynthesis is reciprocal to that of glycogen breakdown. It also has a cascading covalent modification system similar to the glycogen breakdown system described above.
In fact, part of the system is identical to glycogen breakdown. Epinephrine or glucagon signaling stimulates adenylate cyclase to make cAMP, which activates PKA.
In glycogen synthesis, protein kinase A phosphorylates the active form of glycogen synthase GSa , and converts it into the usually inactive b form called GSb. Note the conventions for glycogen synthase and glycogen phosphorylase.
For both enzymes, the more active forms are called the 'a' forms GPa and GSa and the less active forms are called the 'b' forms GPb and GSb. The major difference, however, is that GPa has a phosphate, but GSa does not and GPb has no phosphate, but GSb does.
Thus phosphorylation and dephosphorylation have opposite effects on the enzymes of glycogen metabolism Figure 6. This is the hallmark of reciprocal regulation. It is of note that the less active glycogen synthase form, GSb, can be activated by G6P.
Recall that G6P had the exactly opposite effect on GPb. Glycogen synthase, glycogen phosphorylase and phosphorylase kinase can all be dephosphorylated by the same enzyme - phosphoprotein phosphatase - and it is activated when insulin binds to its receptor in the cell membrane.
In the big picture, binding of epinephrine or glucagon to appropriate cell receptors stimulates a phosphorylation cascade which simultaneously activates breakdown of glycogen by glycogen phosphorylase and inhibits synthesis of glycogen by glycogen synthase.
Epinephrine, is also known as adrenalin, and the properties that adrenalin gives arise from a large temporary increase of blood glucose, which powers muscles. On the other hand, insulin stimulates dephosphorylation by activating phosphoprotein phosphatase. Dephosphorylation reduces action of glycogen phosphorylase less glycogen breakdown and activates glycogen synthase starts glycogen synthesis.
Our bodies make glycogen when blood glucose levels rise. Since high blood glucose levels are harmful, insulin stimulates cells to take up glucose.
In the liver and in muscle cells, the uptaken glucose is made into glycogen. Cellulose is synthesized as a result of catalysis by cellulose synthase.
Like glycogen synthesis it requires an activated intermediate to add glucose residues and there are two possible ones - GDP-glucose and UDPglucose, depending on which cellulose synthase is involved. In plants, cellulose provides support to cell walls.
The GDP-glucose reaction is the same except with substitution of GDP-glucose for UDP-Figure 6. UDP-glucose for the reaction is obtained by catalysis of sucrose synthase.
The enzyme is named for the reverse reaction. The pentose phosphate pathway PPP - also called the hexose monophosphate shunt is an oxidative pathway involving sugars that is sometimes described as a parallel pathway to glycolysis. It is, in fact, a pathway with multiple inputs and outputs Figure 6.
PPP is also a major source of NADPH for biosynthetic reactions and can provide ribosephosphate for nucleotide synthesis.
The multiple entry points and multiple outputs gives the cell tremendous flexibility to meet its needs by allowing it to use a variety of materials to make any of these products. The enzyme catalyzing the reaction is G6P dehydrogenase. It is the rate limiting step of the pathway and the enzyme is inhibited both by NADPH and acetyl-CoA.
NADPH is important for anabolic pathways, such as fatty acid synthesis and also for maintaining glutathione in a reduced state. The latter is important in protection against damage from reactive oxygen species. Deficiency of the G6P dehydrogenase enzyme is not rare, leading to acute hemolytic anemia, due to reduced NADPH concentration, and a reduced ability of the cell to disarm reactive oxygen species with glutathione.
Reduced activity of the enzyme appears to have a protective effect against malarial infection, likely due to the increased fragility of the red blood cell membrane, which is then unable to sustain an infection by the parasite. Hydrolysis Reaction 2 is a hydrolysis and it is catalyzed by.
Reaction 2 is a hydrolysis and it is catalyzed by 6-phosphogluconolactonase. Reaction 3 is the only decarboxylation in the PPP and the last oxidative step. It is catalyzed by 6-phosphogluconate dehydrogenase. Mutations disabling the protein made from this gene negatively impact red blood cells.
At this point, the oxidative phase of PPP is complete and the remaining reactions involve molecular rearrangements. Ru5P has two possible fates and these are each described below. Reaction 4a: The enzyme catalyzing this reversible reaction is Ru5P isomerase top of next column.
It is important because this is the way cells make RP for nucleotide synthesis. The RP can also be used in other PPP reactions shown elsewhere. Reaction 4b catalyzed by RuP epimerase is another source of a pentose sugars and provides an important substrate for subsequent reactions.
It catalyzes the next two reactions. In the first reaction above , two phosphorylated sugars of 5 carbons each are converted into one phosphorylated sugar of 3 carbons and one of 7 carbons.
In the reversible reactions of the pentose phosphate pathway, one can see how glycolysis intermediates can easily be rearranged and made into other sugars. Thus, GLYALP and F6P can be readily made into Ribose phosphate for nucleotide synthesis.
Involvement of F6P in the pathway permits cells to continue making nucleotides by making RP or tryptophan by making E- 4-P even if the oxidative reactions of PPP are inhibited. Transketolase uses thiamine pyrophosphate TPP to catalyze reactions. The stabilized carbanion plays important roles in the reaction mechanism of enzymes, such as transketolase that use TPP as a cofactor.
Commonly, the carbanion acts as a nucleophile that attacks the carbonyl carbon of the substrate. Such is the case with transketolase. In this way, two carbons are moved from Xu- 5-P to EP to make F6P from EP and GLYALP from XuP. Similarly, SP and GLYALP are made from RP and XuP, respectively.
Thiamine was the first water-soluble vitamin B1 to be discovered via association with the peripheral nervous system disease known as Beriberi. Thiamine pyrophosphate TPP is an enzyme cofactor found in all living systems derived from thiamine by action of the enzyme thiamine diphosphokinase.
TPP facilitates catalysis of several biochemical reactions essential for tissue respiration. TPP is required for the oxidative decarboxylation of pyruvate to form acetyl-CoA and similar reactions.
Transketolase, an important enzyme in the pentose phosphate pathway, also uses it as a coenzyme. Besides these reactions, TPP is also required for oxidative decarboxylation of α-keto acids like α-ketoglutarate and branched-chain α-keto acids arising from metabolism of valine, isoleucine, and leucine.
Such action facilitates breaking of carbon-carbon bonds such as occurs during decarboxylation of pyruvate to produce the activated acetaldehyde. Thiamine is integral to respiration and is needed in every cell. Acute deficiency of thiamine leads to numerous problems - the best known condition is beriberi, whose symptoms include weight loss, weakness, swelling, neurological issues, and irregular heart rhythms.
Image by Aleia Kim. Causes of deficiency include poor nutrition, significant intake of foods containing the enzyme known as thiaminase, foods with compounds that counter thiamine action tea, coffee , and chronic diseases, including diabetes, gastrointestinal diseases, persistent vomiting.
People with severe alcoholism often are deficient in thiamine. The Calvin cycle Figure 6. It is in the Calvin cycle of photosynthesis that carbon dioxide is taken from the atmosphere and ultimately built into glucose or other sugars. Reactions of the Calvin cycle take place in regions of the chloroplast known as the stroma, the fluid areas outside of the thylakoid membranes.
The cycle can be broken into three phases. Though reduction of carbon dioxide to glucose ultimately requires electrons from twelve molecules of NADPH and 18 ATPs , it is confusing because one reduction occurs 12 times 1,3 BPG to GLYAL-3P to input the overall reduction necessary to make one glucose.
Another reason students find the pathway confusing is because the carbon dioxide molecules are absorbed one at a time into six different molecules of Ru1,5BP.
At no point are the six carbons ever together in the same molecule to make a single glucose. Instead, six molecules of Ru1,5BP 30 carbons gain six more carbons via carbon dioxide and then split into 12 molecules of 3- phosphoglycerate 36 carbons.
The gain of six carbons allows two three carbon molecules to be produced in excess for each turn of the cycle. These two molecules molecules are then converted into glucose using the enzymes of gluconeogenesis. The other ten molecules of 3-PG are used to regenerate the six molecules of Ru1,5BP.
This reaction is catalyzed by the enzyme known as ribulose-1,5 bisphosphate carboxylase RUBISCO - Figure 6.
The resulting six carbon intermediate is unstable and is rapidly converted to two molecules of 3- phosphoglycerate. As noted, if one starts with 6 molecules of Ru1,5BP and makes 12 molecules of 3-PG, the extra 6 carbons that are a part of the cycle can be shunted off as two three-carbon molecules of glyceraldehydephosphate GLYAL3P to gluconeogenesis, leaving behind 10 molecules to be reconverted into 6 moleFigure 6.
Enzyme numbers explained in text. cules of Ru1,5BP. This occurs in what is called the resynthesis phase. The resynthesis phase Figure 6. RUBISCO is the third and only other enzyme of the pathway that is unique to plants.
All of the other enzymes of the pathway are common to plants and animals and include some found in the pentose phosphate pathway and gluconeogenesis. Humans can consume a variety of carbohydrates, digestion breaks down complex carbohydrates into simple monomers monosaccharides : glucose , fructose , mannose and galactose.
After resorption in the gut , the monosaccharides are transported, through the portal vein , to the liver, where all non-glucose monosacharids fructose, galactose are transformed into glucose as well.
Glycolysis is the process of breaking down a glucose molecule into two pyruvate molecules, while storing energy released during this process as adenosine triphosphate ATP and nicotinamide adenine dinucleotide NADH.
Glycolysis consists of ten steps, split into two phases. Glycolysis can be regulated at different steps of the process through feedback regulation. The step that is regulated the most is the third step.
This regulation is to ensure that the body is not over-producing pyruvate molecules. The regulation also allows for the storage of glucose molecules into fatty acids. The enzymes upregulate , downregulate , and feedback regulate the process.
Gluconeogenesis GNG is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms.
It is one of two primary mechanisms — the other being degradation of glycogen glycogenolysis — used by humans and many other animals to maintain blood sugar levels , avoiding low levels hypoglycemia.
In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis see figure.
For the breakdown of proteins , these substrates include glucogenic amino acids although not ketogenic amino acids ; from breakdown of lipids such as triglycerides , they include glycerol , odd-chain fatty acids although not even-chain fatty acids, see below ; and from other parts of metabolism they include lactate from the Cori cycle.
Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose. The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or guanosine triphosphate GTP , effectively making the process exergonic.
For example, the pathway leading from pyruvate to glucosephosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation.
Glycogenolysis refers to the breakdown of glycogen. Glucosephosphate can then progress through glycolysis. Glucagon in the liver stimulates glycogenolysis when the blood glucose is lowered, known as hypoglycemia. Adrenaline stimulates the breakdown of glycogen in the skeletal muscle during exercise.
Glycogenesis refers to the process of synthesizing glycogen. The pentose phosphate pathway is an alternative method of oxidizing glucose.
Fructose must undergo certain extra steps in order to enter the glycolysis pathway. Lactose, or milk sugar, consists of one molecule of glucose and one molecule of galactose.
Many steps of carbohydrate metabolism allow the cells to access energy and store it more transiently in ATP. Typically, the complete breakdown of one molecule of glucose by aerobic respiration i. involving glycolysis, the citric-acid cycle and oxidative phosphorylation , the last providing the most energy is usually about 30—32 molecules of ATP.
Hormones released from the pancreas regulate the overall metabolism of glucose. The level of circulatory glucose known informally as "blood sugar" , as well as the detection of nutrients in the Duodenum is the most important factor determining the amount of glucagon or insulin produced.
The release of glucagon is precipitated by low levels of blood glucose, whereas high levels of blood glucose stimulates cells to produce insulin. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin.
Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells. Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support e.
chitin , cellulose or for energy storage e. glycogen , starch. However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex.
In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA , which is a feed stock for the fatty acid synthesis pathway; fatty acids , triglycerides , and other lipids are commonly used for long-term energy storage.
The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. Gluconeogenesis permits glucose to be synthesized from various sources, including lipids. In some animals such as termites [20] and some microorganisms such as protists and bacteria , cellulose can be disassembled during digestion and absorbed as glucose.
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Cox, Michael M. New York: W. Freeman and Company. ISBN OCLC Encyclopedia of Food and Health. Guyton and Hall Textbook of Medical Physiology E-Book 13 ed. Elsevier Health Sciences. Lehninger Principles of Biochemistry. USA: Worth Publishers. Archived from the original on August 26, Retrieved September 8, In Reese WO ed.
Dukes' Physiology of Domestic Animals 12th ed. Cornell Univ. PLOS Computational Biology. Bibcode : PLSCB PMC PMID Journal of Cellular Physiology. S2CID Harper's illustrated Biochemistry, 30th edition. USA: McGraw Hill. Clinical Biochemistry. Advanced Nutrition and Human Metabolism.
Cengage Learning. Archives of Biochemistry and Biophysics. ISSN Biochemistry Free for All. Oregon State University. Endocrinology: Adult and Pediatric. A review". The Canadian Veterinary Journal. Bibcode : Natur. Journal of General Microbiology. Metabolism , catabolism , anabolism.
Metabolic pathway Metabolic network Primary nutritional groups. Purine metabolism Nucleotide salvage Pyrimidine metabolism Purine nucleotide cycle. Pentose phosphate pathway Fructolysis Polyol pathway Galactolysis Leloir pathway.
Glycosylation N-linked O-linked. Photosynthesis Anoxygenic photosynthesis Chemosynthesis Carbon fixation DeLey-Doudoroff pathway Entner-Doudoroff pathway. Xylose metabolism Radiotrophism. Fatty acid degradation Beta oxidation Fatty acid synthesis.
Sugad encounter sugar in two different Sugar metabolism in our Sugat sugars that exist in unprocessed foods such Type diabetes complications nerves Muscle-building meals, vegetables, and metaboliism products, and sugars that are metabolusm to packaged Metabolizm to boost flavor metabolisk Sugar metabolism food to Muscle-building meals more shelf-stable. Added sugars are not chemically different from naturally occurring sugars. Both are broken down in the body using the same enzymatic processes. However, the amount and form in which we consume the sugars—in fruits and vegetables, in sodas, or in other processed foods—affects how quickly the body absorbs them, and how the body signals and experiences satiety, or feelings of fullness. They are also chemically similar: more-complex carbohydrates have to be broken into simple sugars before they can be absorbed, transported by the bloodstream, and used for energy. Supports healthy body metabolism and Muscle-building meals rate, along with energy levels. Your metaolism will Muscle-building meals 1 bottle 1 month supply. This subscription will automatically refill every month. Your subscription will include 3 bottles 3 months supply. This subscription will automatically refill every 3 months.Video
Carbohydrate Structure and Metabolism, an Overview, Animation.Sugar metabolism -
Humans can consume a variety of carbohydrates, digestion breaks down complex carbohydrates into simple monomers monosaccharides : glucose , fructose , mannose and galactose.
After resorption in the gut , the monosaccharides are transported, through the portal vein , to the liver, where all non-glucose monosacharids fructose, galactose are transformed into glucose as well.
Glycolysis is the process of breaking down a glucose molecule into two pyruvate molecules, while storing energy released during this process as adenosine triphosphate ATP and nicotinamide adenine dinucleotide NADH.
Glycolysis consists of ten steps, split into two phases. Glycolysis can be regulated at different steps of the process through feedback regulation.
The step that is regulated the most is the third step. This regulation is to ensure that the body is not over-producing pyruvate molecules.
The regulation also allows for the storage of glucose molecules into fatty acids. The enzymes upregulate , downregulate , and feedback regulate the process. Gluconeogenesis GNG is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates.
It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. It is one of two primary mechanisms — the other being degradation of glycogen glycogenolysis — used by humans and many other animals to maintain blood sugar levels , avoiding low levels hypoglycemia.
In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis see figure.
For the breakdown of proteins , these substrates include glucogenic amino acids although not ketogenic amino acids ; from breakdown of lipids such as triglycerides , they include glycerol , odd-chain fatty acids although not even-chain fatty acids, see below ; and from other parts of metabolism they include lactate from the Cori cycle.
Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose. The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or guanosine triphosphate GTP , effectively making the process exergonic.
For example, the pathway leading from pyruvate to glucosephosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation.
Glycogenolysis refers to the breakdown of glycogen. Glucosephosphate can then progress through glycolysis. Glucagon in the liver stimulates glycogenolysis when the blood glucose is lowered, known as hypoglycemia.
Adrenaline stimulates the breakdown of glycogen in the skeletal muscle during exercise. Glycogenesis refers to the process of synthesizing glycogen. The pentose phosphate pathway is an alternative method of oxidizing glucose.
Fructose must undergo certain extra steps in order to enter the glycolysis pathway. Lactose, or milk sugar, consists of one molecule of glucose and one molecule of galactose. Many steps of carbohydrate metabolism allow the cells to access energy and store it more transiently in ATP.
Typically, the complete breakdown of one molecule of glucose by aerobic respiration i. involving glycolysis, the citric-acid cycle and oxidative phosphorylation , the last providing the most energy is usually about 30—32 molecules of ATP.
Hormones released from the pancreas regulate the overall metabolism of glucose. The level of circulatory glucose known informally as "blood sugar" , as well as the detection of nutrients in the Duodenum is the most important factor determining the amount of glucagon or insulin produced.
The release of glucagon is precipitated by low levels of blood glucose, whereas high levels of blood glucose stimulates cells to produce insulin. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin.
Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells. Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support e. chitin , cellulose or for energy storage e. glycogen , starch.
However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex.
In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA , which is a feed stock for the fatty acid synthesis pathway; fatty acids , triglycerides , and other lipids are commonly used for long-term energy storage.
The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. Gluconeogenesis permits glucose to be synthesized from various sources, including lipids.
In some animals such as termites [20] and some microorganisms such as protists and bacteria , cellulose can be disassembled during digestion and absorbed as glucose. Contents move to sidebar hide. Article Talk. Read Edit View history. Tools Tools. What links here Related changes Upload file Special pages Permanent link Page information Cite this page Get shortened URL Download QR code Wikidata item.
Download as PDF Printable version. In other projects. Wikimedia Commons. Biochemical process in living organisms. Surgery Oxford. doi : Lehninger principles of biochemistry.
Cox, Michael M. New York: W. Freeman and Company. ISBN OCLC Encyclopedia of Food and Health. Guyton and Hall Textbook of Medical Physiology E-Book 13 ed. Elsevier Health Sciences. Lehninger Principles of Biochemistry.
USA: Worth Publishers. Archived from the original on August 26, But the atoms are arranged differently, giving the two sugars different chemical properties.
The chemical structures of fructose and glucose influence their sweetness and how they are processed in the body. Fructose tastes twice as sweet as glucose, and sucrose composed of fructose and glucose linked together is somewhere in between.
The proportion of these sugars in foods—both natural and processed—affects how sweet different kinds of sugars taste alone and when added to processed foods. For example, gram for gram, agave nectar tastes sweeter than high fructose corn syrup, which tastes sweeter than sucrose.
Glucose travels through the bloodstream to all of our tissues, and every cell in the body readily burns it for energy. In contrast, fructose is almost exclusively taken up and metabolized by the liver. Excess glucose and fructose are both converted to fat and stored.
However, the fat made from glucose is more likely to end up in fat tissue, whereas fat made from fructose is more likely to accumulate in the liver.
This buildup is called nonalcoholic fatty liver disease, because it looks like what happens in the livers of people who drink too much alcohol. Because agave nectar is made up of pure fructose, it can deliver more sweetness in fewer calories than other sugars, so it may seem like a better choice than table sugar.
However, table sugar may be a healthier choice than agave nectar because it is less likely to cause fat to build up in the liver. Whatever sugar we choose, the key is moderation: any sugar consumed in excess contributes to fat build-up.
Commonly used sugars have different ratios of fructose to glucose. We perceive fructose as tasting twice as sweet as glucose. The amount of glucose circulating in the blood of an average healthy adult is equal to only one or two packets' worth about 5 grams.
Our blood glucose concentration must be kept very stable. When blood sugar levels are too low, the brain can starve. When levels are too high, sensitive tissues in nerves, eyes, and organs can be damaged. To keep blood glucose steady, the body alternates between storing excess glucose after meals and supplying glucose to the blood between meals.
Some glucose is stored in liver and muscle cells as glycogen, and some is converted to fat for storage in adipose tissue. Glycogen and glycerol a component of fat are easily converted back to glucose. However, we cannot make glucose from fatty acids.
The body stores extra fuel as glycogen or fat. Most of our energy reserves are found in fat. While glycogen can be used to replenish blood sugar, fatty acids cannot. Only the small glycerol portion of fat can be converted to glucose, but glycogen is released very slowly only as fatty acids are being burned for fuel.
Unprocessed fruits, vegetables, and whole grains supply moderate amounts of sugar, and they contain other nutrients that make them an important part of a healthy diet. But sugar itself is not an essential nutrient, and when consumed in excess it is a source of completely unnecessary calories.
When the blood glucose concentration falls below that certain point, new glucose is synthesized by the liver to raise the blood concentration to normal. Gluconeogenesis is not simply the reverse of glycolysis. There are some important differences Figure 7.
Pyruvate is a common starting material for gluconeogenesis. First, the pyruvate is converted into oxaloacetate. Oxaloacetate then serves as a substrate for the enzyme phosphoenolpyruvate carboxykinase PEPCK , which transforms oxaloacetate into phosphoenolpyruvate PEP.
From this step, gluconeogenesis is nearly the reverse of glycolysis. PEP is converted back into 2-phosphoglycerate, which is converted into 3-phosphoglycerate. Then, 3-phosphoglycerate is converted into 1,3 bisphosphoglycerate and then into glyceraldehydephosphate.
Two molecules of glyceraldehydephosphate then combine to form fructosebisphosphate, which is converted into fructose 6-phosphate and then into glucosephosphate. Finally, a series of reactions generates glucose itself.
In gluconeogenesis as compared to glycolysis , the enzyme hexokinase is replaced by glucosephosphatase, and the enzyme phosphofructokinase-1 is replaced by fructose-1,6-bisphosphatase. This helps the cell to regulate glycolysis and gluconeogenesis independently of each other.
As will be discussed as part of lipolysis, fats can be broken down into glycerol, which can be phosphorylated to form dihydroxyacetone phosphate or DHAP. DHAP can either enter the glycolytic pathway or be used by the liver as a substrate for gluconeogenesis.
Figure 7. Gluconeogenesis is the synthesis of glucose from pyruvate, lactate, glycerol, alanine, or glutamate. Changes in body composition, including reduced lean muscle mass, are mostly responsible for this decrease.
The most dramatic loss of muscle mass, and consequential decline in metabolic rate, occurs between 50 and 70 years of age. Loss of muscle mass is the equivalent of reduced strength, which tends to inhibit seniors from engaging in sufficient physical activity.
This results in a positive-feedback system where the reduced physical activity leads to even more muscle loss, further reducing metabolism. There are several things that can be done to help prevent general declines in metabolism and to fight back against the cyclic nature of these declines.
These include eating breakfast, eating small meals frequently, consuming plenty of lean protein, drinking water to remain hydrated, exercising including strength training , and getting enough sleep. These measures can help keep energy levels from dropping and curb the urge for increased calorie consumption from excessive snacking.
While these strategies are not guaranteed to maintain metabolism, they do help prevent muscle loss and may increase energy levels. Some experts also suggest avoiding sugar, which can lead to excess fat storage. Spicy foods and green tea might also be beneficial. Because stress activates cortisol release, and cortisol slows metabolism, avoiding stress, or at least practicing relaxation techniques, can also help.
Metabolic enzymes catalyze catabolic reactions that break down carbohydrates contained in food. The energy released is used to power the cells and systems that make up your body.
Excess or unutilized energy is stored as fat or glycogen for later use. Carbohydrate metabolism begins in the mouth, where the enzyme salivary amylase begins to break down complex sugars into monosaccharides.
These can then be transported across the intestinal membrane into the bloodstream and then to body tissues. In the cells, glucose, a six-carbon sugar, is processed through a sequence of reactions into smaller sugars, and the energy stored inside the molecule is released.
The first step of carbohydrate catabolism is glycolysis, which produces pyruvate, NADH, and ATP. Under anaerobic conditions, the pyruvate can be converted into lactate to keep glycolysis working. Under aerobic conditions, pyruvate enters the Krebs cycle, also called the citric acid cycle or tricarboxylic acid cycle.
In addition to ATP, the Krebs cycle produces high-energy FADH 2 and NADH molecules, which provide electrons to the oxidative phosphorylation process that generates more high-energy ATP molecules. For each molecule of glucose that is processed in glycolysis, a net of 36 ATPs can be created by aerobic respiration.
Under anaerobic conditions, ATP production is limited to those generated by glycolysis. While a total of four ATPs are produced by glycolysis, two are needed to begin glycolysis, so there is a net yield of two ATP molecules. In conditions of low glucose, such as fasting, starvation, or low carbohydrate diets, glucose can be synthesized from lactate, pyruvate, glycerol, alanine, or glutamate.
This process, called gluconeogenesis, is almost the reverse of glycolysis and serves to create glucose molecules for glucose-dependent organs, such as the brain, when glucose levels fall below normal.
salivary amylase: digestive enzyme that is found in the saliva and begins the digestion of carbohydrates in the mouth. cellular respiration: production of ATP from glucose oxidation via glycolysis, the Krebs cycle, and oxidative phosphorylation.
glycolysis: series of metabolic reactions that breaks down glucose into pyruvate and produces ATP. pyruvate: three-carbon end product of glycolysis and starting material that is converted into acetyl CoA that enters the.
Krebs cycle: also called the citric acid cycle or the tricarboxylic acid cycle, converts pyruvate into CO 2 and high-energy FADH 2 , NADH, and ATP molecules. citric acid cycle or tricarboxylic acid cycle TCA : also called the Krebs cycle or the tricarboxylic acid cycle; converts pyruvate into CO 2 and high-energy FADH 2 , NADH, and ATP molecules.
energy-consuming phase , first phase of glycolysis, in which two molecules of ATP are necessary to start the reaction. glucosephosphate: phosphorylated glucose produced in the first step of glycolysis. Hexokinase: cellular enzyme, found in most tissues, that converts glucose into glucosephosphate upon uptake into the cell.
Glucokinase: cellularenzyme, found in the liver, which converts glucose into glucosephosphate upon uptake into the cell. energy-yielding phase: second phase of glycolysis, during which energy is produced. terminal electron acceptor: ATP production pathway in which electrons are passed through a series of oxidation-reduction reactions that forms water and produces a proton gradient.
electron transport chain ETC : ATP production pathway in which electrons are passed through a series of oxidation-reduction reactions that forms water and produces a proton gradient. oxidative phosphorylation: process that converts high-energy NADH and FADH 2 into ATP.
Skip to main content. Module 8: Metabolism and Nutrition. Search for:. Carbohydrate Metabolism Learning Objectives By the end of this section, you will be able to: Explain the processes of glycolysis Describe the pathway of a pyruvate molecule through the Krebs cycle Explain the transport of electrons through the electron transport chain Describe the process of ATP production through oxidative phosphorylation Summarize the process of gluconeogenesis.
Watch this video to learn about glycolysis:. Watch this animation to observe the Krebs cycle. Watch this video to learn about the electron transport chain. Critical Thinking Questions Explain how glucose is metabolized to yield ATP.
gov means it's Sugar metabolism. Federal government websites often end in. Fueling up in-game or. Before Metaolism sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
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