Growth of the ropy and non-ropy strains was accompanied by total release of the galactose moiety from lactose hydrolysis in modified Bellinker broth with lactose as the only carbon source.

This was associated with a greater exopolysaccharide production by the ropy strain. The polymer produced by both strains in cultures with lactose or glucose as carbon sources contained glucose, galactose and rhamnose, indicating that glucose was used as a carbon source for bacterial growth and for exopolysaccharide formation.

Biochem Genet — Mitchell B, Haigis E, Steinmann B, Gitzelmann R Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture. Proc Natl Acad Sci U S A — Ng WG, Donnel GN, Hodgman JE, Bergren WR Differences in uridine diphosphate galactoseepimerase between haemolysates of newborns and of adults.

Nature — Okumiya T, Keulemans JLM, Kroos MA, Van der Beek NME, Boer MA, Takeuchi H, Van Diggelen OP, Reuser AJJ A new diagnostic assay for glycogen storage disease type II in mixed leukocytes. Mol Genet Metab — Seifter S, Dayton S, Novic B, Muntwyler E The estimation of glycogen with the anthrone reagent.

Arch Biochem — Steinmann B, Gitzelmann R, Van den Berghe G Disorders of fructose metabolism. Thomas JA, Schlender KK, Larner J A rapid filter paper assay for UDP-glucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP- 14 C-glucose. Uyttenhove K, Bollen M, Stalmans W An optimized assay of phosphorylase kinase in crude liver preparations.

Van Hoof F Amylo-1,6-glucosidase activity and normal glycogen content of the erythrocytes of normal subjects, patients with glycogen storage disease and heterozygotes. CrossRef PubMed Google Scholar. Vora S, Corash L, Engel WK, Durham S, Seaman C, Piomelli S The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy.

Blood — Download references. You can also search for this author in PubMed Google Scholar. Academic Medical Centre, Lab. Genetic Metabolic; Diseases Fo, University Amsterdam, Meibergdreef 9, AZ, Amsterdam, Netherlands. Reprints and permissions.

Bosshard, N. Enzymes and Metabolites of Carbohydrate Metabolism. In: Blau, N. eds Laboratory Guide to the Methods in Biochemical Genetics. Springer, Berlin, Heidelberg. Publisher Name : Springer, Berlin, Heidelberg. Print ISBN : Online ISBN : eBook Packages : Medicine Medicine R0.

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Provided by the Springer Nature SharedIt content-sharing initiative. Policies and ethics. Skip to main content. Abstract This chapter deals with the assays used for the diagnosis of three groups of inborn errors of metabolism of carbohydrates, i. Glycogenoses, or glycogen storage diseases GSD a.

Type Ia, deficiency of glucosephosphatase b. Type II, deficiency of α-glucosidase acid maltase c. Type III, deficiency of amylo-1,6-glucosidase debranching enzyme d. Type IV, deficiency of 1,4-glucan branching enzyme e. Type V, deficiency of myophosphorylase f.

Type VI, deficiency of liver phosphorylase g. Type VII, deficiency of phosphofructokinase h. Type IX, deficiency of phosphorylase b-kinase i. Type 0, deficiency of glycogen synthase.

Keywords DEAE Cellulose Glycogen Storage Disease Nicotinamide Adenine Dinucleotide Debranching Enzyme Classical Galactosemia These keywords were added by machine and not by the authors. Buying options Chapter EUR eBook EUR Tax calculation will be finalised at checkout Purchases are for personal use only Learn about institutional subscriptions.

Preview Unable to display preview. References Baker L, Winegrad AI Fasting hypoglycaemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-diphosphatase activity.

Lancet ii—16 CrossRef Google Scholar Bergren WR, Ng WG, Donnel GN Uridine diphosphate galactoseepimerase in human and other mammalian haemolysates. Biochim Biophys Acta — Google Scholar Besley GTN Phosphorylase b kinase deficiency in glycogenosis type VIII: differentiation of different phenotypes and heterozygotes by erythrocyte enzyme assay.

J Inherit Metab Dis — CrossRef PubMed CAS Google Scholar Beutler E Red Cell Metabolism, 2nd edn. Further study is necessary to determine whether these results can be verified in vivo using animal models such as liver-specific knock-in mice for S7A liver glycogen synthase.

The protein phosphatase 1 PP1 may be responsible for the dephosphorylation and activation of glycogen synthase. Accordingly, both glucose and insulin have been shown to activate PP1 activity, whereas glucagon and epinephrine have been linked to the inhibition of its activity.

Glycogen phosphorylase is a major enzyme involved in glycogenolysis Figure 1. This enzyme catalyzes the reaction of the removal of a glucose residue from the non-reducing end of a glycogen chain, leading to the generation of glucose 1-phosphate.

Glycogen phosphorylase is active when it is phosphorylated at its serine 14 residue. The phosphorylation of glycogen phosphorylase requires a cascade mechanism of epinephrine and glucagon in the liver.

On the activation of Gαs by the binding of hormones to cell surface G protein-coupled receptors beta adrenergic receptor or glucagon receptor , the intracellular cyclic AMP cAMP levels increase via adenylate cyclase, leading to the activation of PKA.

PKA is then responsible for the phosphorylation and activation of glycogen phosphorylase kinase, which in turn phosphorylates and activates glycogen phosphorylase to enhance glycogen breakdown.

Under feeding conditions, this kinase cascade is inactive due to the lack of secretion of catabolic hormones. In addition, insulin promotes the activation of PP1, which dephosphorylates and inactivates glycogen phosphorylase.

In essence, the anabolic hormone insulin promotes glycogenesis and inhibits glycogenolysis via the activation of PP1, leading to the dephosphorylation of glycogen phosphorylase inactivation and glycogen synthase activation , and via the activation of Akt, leading to the phosphorylation of GSK-3 inactivation that is unable to phosphorylate and inactivate glycogen synthase.

As stated above, glycolysis is critical to the catabolism of glucose in most cells to generate energy. The key rate-limiting enzymes for this pathway include glucokinase GK, also termed hexokinase IV , which converts glucose into glucose 6-phosphate; phosphofructokinase-1 PFK-1 , which converts fructose 6-bisphosphate into fructose 1,6-bisphosphate; and liver-type pyruvate kinase L-PK , which converts phosphoenolpyruvate PEP into pyruvate in the liver.

These enzymes are tightly regulated by allosteric mediators that generally promote the catabolism of glucose in the cell. GK is a high Km hexokinase that is present in the liver and the pancreatic beta cells, thus functioning as a glucose sensor for each cell type.

Unlike the other hexokinase isotypes, GK activity is not allosterically inhibited by its catalytic product, glucose 6-phosphate in the cell, thus enabling the liver to continuously utilize glucose for glycolysis during conditions of increased glucose availability, such as during feeding conditions.

GK is regulated via its interaction with glucokinase regulatory protein GKRP. In the low intracellular glucose concentration during fasting, the binding of GK and GKRP is enhanced by fructose 6-phosphate, leading to the nuclear localization of this protein complex.

Higher concentrations of glucose during feeding compete with fructose 6-phosphate to bind this complex, which promotes the cytosolic localization of GK that is released from GKRP, thus causing the increased production of glucose 6-phosphate in this setting.

PFK-1 catalyzes the metabolically irreversible step that essentially commits glucose to glycolysis. This enzyme activity is allosterically inhibited by ATP and citrate, which generally indicate a sign of energy abundance. Reciprocally, it is allosterically activated by ADP or AMP, making it more efficient to bring about glycolysis to produce more ATP in the cell.

In addition, PFK-1 activity is allosterically activated by fructose 2,6-bisphosphate F26BP , a non-glycolytic metabolite that is critical for the regulation of glucose metabolism in the liver.

F26BP is generated from fructose 6-phosphate by the kinase portion of a bifunctional enzyme that contains both a kinase domain phosphofructokinase-2, PFK-2 and a phosphatase domain fructose 2,6-bisphosphatase, F-2,6-Pase.

PFK-2 is activated by the insulin-dependent dephosphorylation of a bifunctional enzyme that activates PFK-2 activity and simultaneously inhibits F-2,6-Pase activity to promote the increased F26BP concentration.

Glucagon-mediated activation of PKA is shown to be responsible for the phosphorylation and inactivation of the kinase portion of this enzyme. Unlike its muscle counterpart, L-PK is also a critical regulatory step in the control of glycolysis in the liver.

As in the case of other glycolytic enzymes, L-PK activity is regulated by both allosteric mediators and post-translational modifications. L-PK activity is allosterically activated by fructose 1,6-bisphosphate, an indicator for the active glycolysis.

By contrast, its activity is allosterically inhibited by ATP, acetyl-CoA, and long-chain fatty acids, all of which signal an abundant energy supply.

Additionally, the amino acid alanine inhibits its activity, as it can be readily converted to pyruvate by a transamination reaction.

L-PK is inhibited by PKA following a glucagon-mediated increase in intracellular cAMP during fasting and is activated by insulin-mediated dephosphorylation under feeding conditions. In addition to the acute regulation of key regulatory enzymes, glycolysis is regulated by a transcriptional mechanism that is activated during feeding conditions.

Two major transcription factors, sterol regulatory element binding protein 1c SREBP-1c and carbohydrate response element binding protein ChREBP , are responsible for the transcriptional activation of not only glycolytic enzyme genes but also the genes involved in fatty acid biosynthesis such as fatty acid synthase FAS , acetyl-CoA carboxylase ACC , and stearoyl-CoA desaturase 1 SCD1 and triacylglycerol formation such as glycerol 3-phosphate acyltransferase GPAT and diacylglycerol acyltransferase 2 DGAT2 , a process that is normally activated by a carbohydrate-rich diet Figure 2.

Regulation of hepatic glycolysis. Under feeding conditions, increased glucose uptake in hepatocytes promotes glycolysis and lipogenesis to generate triglycerides as storage forms of fuel. This process is transcriptionally regulated by two major transcription factors in the liver, SREBP-1c and ChREBP-Mlx heterodimer, which mediate the insulin and glucose response, respectively.

SREBPs are the major regulators of lipid metabolism in mammals. SREBP is translated as an endoplasmic reticulum ER -bound precursor form that contains the N-terminal transcription factor domain and the C-terminal regulatory domain linked with the central transmembrane domain.

SREBP-1c, however, activates the genes encoding the enzymes for lipogenesis FAS, ACC, SCD1, and DGAT2 as well as GK, which is a first enzyme in the commitment step of glucose utilization in the liver.

Indeed, liver-specific SREBP-1c knockout mice showed an impaired activation of lipogenic genes in a high carbohydrate diet, thus confirming the importance of this transcription factor in the regulation of hepatic glycolysis and fatty acid biosynthesis.

The expression of SREBP-2 is not controlled by sterols, but its proteolytic processing is tightly regulated by intracellular concentrations of cholesterol. The exact transcription factor that mediates this insulin-dependent signal is not yet clear, although SREBP-1c itself might be involved in the process as part of an auto-regulatory loop.

Interestingly, the oxysterol-sensing transcription factor liver X receptor LXR is shown to control the transcription of SREBP-1c, suggesting that SREBP-1c and SREBP-2 could be regulated differently in response to cellular cholesterol levels.

In HepG2 cells, PKA was shown to reduce the DNA binding ability of SREBP-1a by the phosphorylation of serine equivalent of serine for SREBP-1c. The other prominent transcription factor for controlling glycolysis and fatty acid biosynthesis in the liver is ChREBP.

ChREBP was initially known as Williams-Beuren syndrome critical region 14 WBSCR14 and was considered one of the potential genes that instigate Williams-Beuren syndrome. Later, by using a carbohydrate response element ChoRE from L-PK, ChREBP was isolated as a bona fide transcription factor for binding ChoRE of glycolytic promoters.

A recent report indeed suggested a role for LXR in the transcriptional activation of ChREBP in response to glucose, although the study needs to be further verified because the transcriptional response is shown not only by the treatment of D-glucose, a natural form of glucose present in animals, but also by the treatment of unnatural L-glucose, a form of glucose that is not known to activate lipogenesis in the liver.

PKA is shown to phosphorylate serine , which is critical for cellular localization, and threonine , which is critical for its DNA binding ability, whereas AMPK phosphorylate serine dictates its DNA binding ability. All three sites are phosphorylated under fasting conditions by these kinases and are dephosphorylated under feeding by xylulose 5-phosphate X5P -mediated activity of protein phosphatase 2A PP2A.

First, high glucose concentrations in primary hepatocytes do not result in decreased cAMP levels or PKA activity, suggesting that other signals might be necessary to mediate the high glucose-dependent nuclear translocation of ChREBP.

ChREBP knockout mice were born in a Mendelian ratio and showed no developmental problems. The knockout animals showed reduced liver triacylglycerol levels together with a reduction in lipogenic gene expression, thus confirming the role of ChREBP in the control of hepatic glycolysis and fatty acid synthesis.

Prolonged fasting or starvation induces de novo glucose synthesis from non-carbohydrate precursors, termed hepatic gluconeogenesis. This process initiates from the conversion of pyruvate to oxaloacetate by pyruvate carboxylase PC in the mitochondria and eventually concludes in the conversion into glucose via several enzymatic processes in the cytosol.

Key regulatory enzymes in that pathway, including glucose 6-phosphatase G6Pase , fructose 1,6-bisphosphatase Fbpase1 , PC, and phosphoenolpyruvate carboxykinase PEPCK , are activated under fasting conditions to enhance gluconeogenic flux in that setting.

Mitochondrial acetyl-CoA derived from the increased fatty acid oxidation under fasting functions as a key allosteric activator of PC, leading to the increased production of oxaloacetate for the gluconeogenesis. In addition, F26BP, which is a key allosteric regulator for glycolysis by activating PFK-1, was shown to inhibit gluconeogenesis via the allosteric inhibition of Fbpase1, which helps reciprocally control gluconeogenesis and glycolysis under different dietary statuses.

Because Fbpase2 is activated but PFK-2 is inhibited under fasting, the lack of F26BP enables the activation of Fbpase1 and the increased production of fructose 6-phosphate in gluconeogenesis. The chronic activation of gluconeogenesis is ultimately achieved via transcriptional mechanisms.

Major transcriptional factors that are shown to induce gluconeogenic genes include CREB, FoxO1, and several nuclear receptors Figure 3. Regulation of hepatic gluconeogenesis. Under fasting conditions, hepatic gluconeogenesis is enhanced via a decreased concentration of insulin and an increased concentration of insulin counterregulatory hormones such as glucagon.

FoxO1, forkhead box O 1. Under fasting conditions, glucagon and epinephrine can increase the cAMP concentration in the liver via the activation of adenylate cyclase, leading to the activation of PKA and the subsequent induction of CREB via its serine phosphorylation.

In contrast, the role for CBP in gluconeogenesis is still controversial. Disruption of CREB-CBP interaction does not appear to affect glucose homeostasis because mice exhibiting a stable expression of mutant CBP that was unable to bind CREB showed normal glycemia.

The CRTC family of transcriptional coactivators consists of CRTC1, CRTC2 and CRTC3, which were isolated by the expression library screening as activaters of CREB-dependent transcription.

Recent studies have delineated the role of CRTC2 in the regulation of hepatic gluconeogenesis in vivo. Knockdown of CRTC2 in mice by RNAi reduced blood glucose levels and led to a concomitant repression of gluconeogenic gene expression.

The forkhead box O FoxOs belongs to a class of forkhead families of transcription, which recognize the AT-rich insulin response element on the promoter. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha PGC-1α , a known coactivator for nuclear receptors, functions as a key transcriptional coactivator for FoxO1 in hepatic gluconeogenesis.

In this case, PRMT1 promotes the asymmetric dimethylation of arginine and in FoxO1, which blocks the binding of Akt and the subsequent Akt-mediated phosphorylation of the adjacent serine residue serine , thus enhancing the nuclear localization of FoxO1.

Nuclear receptors belong to the superfamily of transcription factors that possess two Cys2-His2 type zinc finger motifs as a DNA binding domain as well as both ligand-independent and ligand-dependent transactivation domains. Nuclear receptors can be classified into one of three subgroups based on their dimer-forming potential.

Homodimeric nuclear receptors are also called cytosolic receptors because they reside in the cytosol and associate with molecular chaperones such as heat-shock proteins.

On binding to the ligand, they form homodimers and translocate to the nucleus to bind a specific response element termed the hormone response element to elicit the ligand-dependent transcriptional response.

Most of the steroid hormone receptors, such as the glucocorticoid receptor GR , estrogen receptor ER , and progesterone receptor PR , belong to this subfamily. By contrast, heterodimeric nuclear receptors reside in the nucleus and are bound to their cognate binding sites together with the universal binding partner retinoid X receptor RXR.

Examples of this class of nuclear receptors include members of peroxisome proliferator-activated receptors, LXRs, vitamin D receptors and thyroid hormone receptors. The final subclasses of nuclear receptors are types that function as monomers.

They usually lack specific endogenous ligands and are often called orphan nuclear receptors. Some of them also lack DNA binding domain and thus function as transcriptional repressors of various transcription factors, including members of nuclear receptors.

They are called atypical orphan nuclear receptors. Among the homodimeric nuclear receptors, the role of GR has been linked to the control of hepatic gluconeogenesis. GR is activated by cortisol, which is released from the adrenal cortex in response to chronic stresses such as prolonged fasting.

The same response elements were also shown to be recognized and regulated by hepatocyte nuclear factor 4 HNF4 , a member of heterodimeric nuclear receptors, which suggests that these nuclear receptors could coordinately function to control hepatic gluconeogenesis in response to fasting.

In accordance with this idea, the activity of these nuclear receptors can be effectively integrated by the function of transcriptional co-activator PGC-1α. Recently, estrogen-related receptor gamma ERRγ , a member of monomeric nuclear receptors, was shown to be involved in the regulation of hepatic gluconeogenesis.

This factor regulates hepatic gluconeogenesis by binding to unique response elements that are distinct from the known nuclear receptor-binding sites in the promoters of PEPCK and G6Pase. Inhibition of ERRγ activity by injecting either RNAi or the inverse agonist GSK effectively reduced hyperglycemia in diabetic mice, suggesting that the control of this factor might potentially be beneficial in the treatment of patients with metabolic diseases.

As is the case for other nuclear receptors that control hepatic gluconeogenesis, ERRγ activity is further enhanced by interaction with the transcriptional coactivator PGC-1α, showing that this coactivator functions as a master regulator for the hepatic glucose metabolism.

Three members of atypical orphan nuclear receptors, the small heterodimer partner SHP, also known as NR0B2 ; the dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X DAX-1, also known as NR0B1 ; and the SHP-interacting leucine zipper protein SMILE are implicated in the transcriptional repression of hepatic gluconeogenesis.

Interestingly, metformin directly activates the transcription of SHP via an AMPK-mediated pathway. SHP directly inhibits cAMP-dependent transcription by binding to CREB, resulting in the reduced association of CREB with CRTC2.

These results provide a dual mechanism for a metformin-AMPK dependent pathway to inhibit hepatic gluconeogenesis at the transcriptional level; an acute regulation of CRTC2 phosphorylation to inhibit the CRTC2-CREB-dependent transcriptional circuit; and a longer-term regulation of gluconeogenic transcription by enhanced SHP expression.

Both DAX-1 and SMILE were shown to repress hepatic gluconeogenesis by inhibiting HNF4-dependent transcriptional events.

Interestingly, SMILE was shown to directly replace PGC-1α from HNF4 and the gluconeogenic promoters, suggesting that this factor could potentially function as a major transcriptional repressor of hepatic gluconeogenesis in response to insulin signaling.

Further study is necessary to fully understand the relative contribution of these nuclear receptors in the control of glucose homeostasis in both physiological conditions and pathological settings. In this review, we attempted to describe the current understanding of the regulation of glucose metabolism in the mammalian liver.

Under feeding conditions, glucose, a major hexose monomer of dietary carbohydrate, is taken up in the liver and oxidized via glycolysis. The excess glucose that is not utilized as an immediate fuel for energy is stored initially as glycogen and is later converted into triacylglycerols via lipogenesis.

Glycogenesis is activated via the insulin-Akt-mediated inactivation of GSK-3, leading to the activation of glycogen synthase and the increased glycogen stores in the liver. Insulin is also critical in the activation of PP1, which functions to dephosphorylate and activate glycogen synthase. Glycolysis is controlled by the regulation of three rate-limiting enzymes: GK, PFK-1 and L-PK.

The activities of these enzymes are acutely regulated by allosteric regulators such as ATP, AMP, and F26BP but are also controlled at the transcription level.

Two prominent transcription factors are SREBP-1c and ChREBP, which regulate not only the aforementioned glycolytic enzyme genes but also the genes encoding enzymes for fatty acid biosynthesis and triacylglycerol synthesis collectively termed as lipogenesis.

The importance of these transcription factors in the control of glycolysis and fatty acid biosynthesis has been verified by knockout mouse studies, as described in the main text. The liver also has a critical role in controlling glucose homeostasis under fasting conditions.

Initially, insulin counterregulatory hormones such as glucagon and epinephrine are critical in activating the PKA-driven kinase cascades that promote glycogen phosphorylase and glycogenolysis in the liver, thus enabling this tissue to provide enough fuel for peripheral tissues such as the brain, red blood cells and muscles.

Subsequently, these hormones together with adrenal cortisol are crucial in initiating the transcriptional activation of gluconeogenesis such as PC, PEPCK and G6Pase. The major transcription factors involved in the pathway include CREB, FoxO1 and members of nuclear receptors, with aid from transcriptional coactivators such as CRTC, PGC-1α and PRMTs.

These adaptive responses are critical for maintaining glucose homeostasis in times of starvation in mammals. Further study is necessary by using liver-specific knockout mice for each regulator of hepatic glucose metabolism to provide better insights into the intricate control mechanisms of glucose homeostasis in mammals.

Nordlie RC, Foster JD, Lange AJ. Regulation of glucose production by the liver. Annul Rev Nutr ; 19 : — Article CAS Google Scholar. Towle HC, Kaytor EN, Shih HM. Regulation of the expression of lipogenic enzyme genes by carbohydrate.

Annu Rev Nutr ; 17 : — Article CAS PubMed Google Scholar. Roach PJ. Glycogen and its metabolism. Curr Mol Med ; 2 : — van de Werve G, Jeanrenaud B.

Liver glycogen metabolism: an overview. Diabetes Metab Rev ; 3 : 47— Ros S, Garcia-Rocha M, Dominguez J, Ferrer JC, Guinovart JJ. Control of liver glycogen synthase activity and intracellular distribution by phosphorylation.

The J Biol Chem ; : — Agius L. Role of glycogen phosphorylase in liver glycogen metabolism. Mol Aspects Med ; 46 : 34— Pilkis SJ, Claus TH. Annu Rev Nutr ; 11 : — Pilkis SJ, Claus TH, el-Maghrabi MR. The role of cyclic AMP in rapid and long-term regulation of gluconeogenesis and glycolysis.

Adv Second Messenger Phosphoprotein Res ; 22 : — CAS PubMed Google Scholar. Pilkis SJ, el-Maghrabi MR, Claus TH. Hormonal regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Biochem ; 57 : — Brouwers MC, Jacobs C, Bast A, Stehouwer CD, Schaper NC.

Modulation of glucokinase regulatory protein: a double-edged sword? Trends Mol Med ; 21 : — Dentin R, Girard J, Postic C. Carbohydrate responsive element binding protein ChREBP and sterol regulatory element binding protein-1c SREBP-1c : two key regulators of glucose metabolism and lipid synthesis in liver.

Biochimie ; 87 : 81— Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest ; : — Article CAS PubMed PubMed Central Google Scholar. Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y et al.

The following discussions of glycolysis include the enzymes responsible for the reactions. When glucose enters a cell, the enzyme hexokinase or glucokinase, in the liver rapidly adds a phosphate to convert it into glucosephosphate.

A kinase is a type of enzyme that adds a phosphate molecule to a substrate in this case, glucose, but it can be true of other molecules also. This conversion step requires one ATP and essentially traps the glucose in the cell, preventing it from passing back through the plasma membrane, thus allowing glycolysis to proceed.

It also functions to maintain a concentration gradient with higher glucose levels in the blood than in the tissues. By establishing this concentration gradient, the glucose in the blood will be able to flow from an area of high concentration the blood into an area of low concentration the tissues to be either used or stored.

Hexokinase is found in nearly every tissue in the body. Glucokinase , on the other hand, is expressed in tissues that are active when blood glucose levels are high, such as the liver.

Hexokinase has a higher affinity for glucose than glucokinase and therefore is able to convert glucose at a faster rate than glucokinase. This is important when levels of glucose are very low in the body, as it allows glucose to travel preferentially to those tissues that require it more.

In the next step of the first phase of glycolysis, the enzyme glucosephosphate isomerase converts glucosephosphate into fructosephosphate. Like glucose, fructose is also a six carbon-containing sugar. The enzyme phosphofructokinase-1 then adds one more phosphate to convert fructosephosphate into fructosebisphosphate, another six-carbon sugar, using another ATP molecule.

Aldolase then breaks down this fructosebisphosphate into two three-carbon molecules, glyceraldehydephosphate and dihydroxyacetone phosphate.

The triosephosphate isomerase enzyme then converts dihydroxyacetone phosphate into a second glyceraldehydephosphate molecule. Therefore, by the end of this chemical- priming or energy-consuming phase, one glucose molecule is broken down into two glyceraldehydephosphate molecules.

The second phase of glycolysis, the energy-yielding phase , creates the energy that is the product of glycolysis. Glyceraldehydephosphate dehydrogenase converts each three-carbon glyceraldehydephosphate produced during the. energy-consuming phase into 1,3-bisphosphoglycerate.

NADH is a high-energy molecule, like ATP, but unlike ATP, it is not used as energy currency by the cell. Because there are two glyceraldehydephosphate molecules, two NADH molecules are synthesized during this step.

Each 1,3-bisphosphoglycerate is subsequently dephosphorylated i. Each phosphate released in this reaction can convert one molecule of ADP into one high- energy ATP molecule, resulting in a gain of two ATP molecules.

The enzyme phosphoglycerate mutase then converts the 3-phosphoglycerate molecules into 2-phosphoglycerate. The enolase enzyme then acts upon the 2-phosphoglycerate molecules to convert them into phosphoenolpyruvate molecules.

The last step of glycolysis involves the dephosphorylation of the two phosphoenolpyruvate molecules by pyruvate kinase to create two pyruvate molecules and two ATP molecules.

In summary, one glucose molecule breaks down into two pyruvate molecules, and creates two net ATP molecules and two NADH molecules by glycolysis. Therefore, glycolysis generates energy for the cell and creates pyruvate molecules that can be processed further through the aerobic Krebs cycle also called the citric acid cycle or tricarboxylic acid cycle ; converted into lactic acid or alcohol in yeast by fermentation; or used later for the synthesis of glucose through gluconeogenesis.

When oxygen is limited or absent, pyruvate enters an anaerobic pathway. In these reactions, pyruvate can be converted into lactic acid. In this reaction, lactic acid replaces oxygen as the final electron acceptor.

Anaerobic respiration occurs in most cells of the body when oxygen is limited or mitochondria are absent or nonfunctional. For example, because erythrocytes red blood cells lack mitochondria, they must produce their ATP from anaerobic respiration.

This is an effective pathway of ATP production for short periods of time, ranging from seconds to a few minutes. The lactic acid produced diffuses into the plasma and is carried to the liver, where it is converted back into pyruvate or glucose via the Cori cycle.

Similarly, when a person exercises, muscles use ATP faster than oxygen can be delivered to them. They depend on glycolysis and lactic acid production for rapid ATP production. The NADH and FADH2 pass electrons on to the electron transport chain, which uses the transferred energy to produce ATP.

As the terminal step in the electron transport chain, oxygen is the terminal electron acceptor and creates water inside the mitochondria. Figure 3. Click to view a larger image. The process of anaerobic respiration converts glucose into two lactate molecules in the absence of oxygen or within erythrocytes that lack mitochondria.

During aerobic respiration, glucose is oxidized into two pyruvate molecules. The pyruvate molecules generated during glycolysis are transported across the mitochondrial membrane into the inner mitochondrial matrix, where they are metabolized by enzymes in a pathway called the Krebs cycle Figure 4.

The Krebs cycle is also commonly called the citric acid cycle or the tricarboxylic acid TCA cycle. During the Krebs cycle, high-energy molecules, including ATP, NADH, and FADH2, are created.

NADH and FADH2 then pass electrons through the electron transport chain in the mitochondria to generate more ATP molecules. Figure 4. During the Krebs cycle, each pyruvate that is generated by glycolysis is converted into a two-carbon acetyl CoA molecule.

The acetyl CoA is systematically processed through the cycle and produces high- energy NADH, FADH2, and ATP molecules. The three-carbon pyruvate molecule generated during glycolysis moves from the cytoplasm into the mitochondrial matrix, where it is converted by the enzyme pyruvate dehydrogenase into a two-carbon acetyl coenzyme A acetyl CoA molecule.

This reaction is an oxidative decarboxylation reaction. Acetyl CoA enters the Krebs cycle by combining with a four-carbon molecule, oxaloacetate, to form the six-carbon molecule citrate, or citric acid, at the same time releasing the coenzyme A molecule.

The six-carbon citrate molecule is systematically converted to a five-carbon molecule and then a four-carbon molecule, ending with oxaloacetate, the beginning of the cycle. Along the way, each citrate molecule will produce one ATP, one FADH2, and three NADH.

The FADH2 and NADH will enter the oxidative phosphorylation system located in the inner mitochondrial membrane. In addition, the Krebs cycle supplies the starting materials to process and break down proteins and fats.

To start the Krebs cycle, citrate synthase combines acetyl CoA and oxaloacetate to form a six-carbon citrate molecule; CoA is subsequently released and can combine with another pyruvate molecule to begin the cycle again.

The aconitase enzyme converts citrate into isocitrate. In two successive steps of oxidative decarboxylation, two molecules of CO2 and two NADH molecules are produced when isocitrate dehydrogenase converts isocitrate into the five-carbon α-ketoglutarate, which is then catalyzed and converted into the four-carbon succinyl CoA by α-ketoglutarate dehydrogenase.

The enzyme succinyl CoA dehydrogenase then converts succinyl CoA into succinate and forms the high-energy molecule GTP, which transfers its energy to ADP to produce ATP. Succinate dehydrogenase then converts succinate into fumarate, forming a molecule of FADH2.

Oxaloacetate is then ready to combine with the next acetyl CoA to start the Krebs cycle again see Figure 4. For each turn of the cycle, three NADH, one ATP through GTP , and one FADH2 are created. Each carbon of pyruvate is converted into CO2, which is released as a byproduct of oxidative aerobic respiration.

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Otolaryngology ENT. Chemical Pathology. The evidence presented suggests that the glucose moiety from lactose hydrolysis is the source of sugar for heteropolysaccharide synthesis, due to a high UDP-glucose pyrophosphorylase activity.

Abstract The role of the enzymes uridine-5'-diphospho- UDP glucose pyrophosphorylase and UDP galactose 4-epimerase in exopolysaccharide production of Gal- ropy and non-ropy strains of Streptococcus thermophilus in a batch culture was investigated.

Publication types Comparative Study Research Support, Non-U.