Overheads for Section A brief interlude on digestion Overview of digestion More digestion facts Overview of biochemical pathways Chapter 14 Glycolysis The glycolytic pathway Another view of the glycolytic pathway The test version Details of one individual reaction step Enzyme compexes facilitate channeling The energy landscape of glycolysis The "metabolic" regulation of glycolysis Glycolytic addenda Other carboyhdrates are funneled into the glycolytic path Use of galactose The fates of pyruvate Gluconeogenesis Gluconeogenesis-b Pyr to PEP Two other bypasses Gluconeogenesis and mitochondria The Pentose pathway Alternative views of the Pentose pathway Chapter 15 The role of glycogen phosphorylase The mechanism of GP The breakdown of glycogen Transporting glucose to the blood Activating glucose for synthesis The synthesis of glycogen Regulation of GP The alloseric regulation of PFK Coordinate regulation of PFK and FBP The role of F2,6BP Pyruvate Kinase is regulated Coordinate regulation of glycolysis/gluconeogenesis Hormonal influence on glucose metabolism Glycogen synthase is regulated by hormones Synthesis and hydrolysis of F2,6BP More on PFK2 and FBPase2 Summary of hormone regulation in the liver Chapter 16 The TCA cycle in metabolism Some headlines in C-C chemistry C C bond reactions in biochemistry Enolate stabilization in carbon-carbon bonds TPP modifies α-keto acids for decarboxylation TPP and decarboxylation Back to Metabolism The PDC "linking step" PDC is a geometric complex Regulation of PDC Steps of the TCA cycle The test version Mech of citrate synthase, more C-C chem The energy profile of TCA Regulation of the TCA cycle Depletion of TCA intermediates The anaplerotic reactions Chemistry of pryuvate carboxylase The aerobic metabolism of glucose The glyoxylate cycle The glyoxylate shunt Linking TCA and glyoxylate shunt Chapter 17 Lipids from ingestion, storage, or synthesis Fat uptake Lipid mobilization Chylomicrons Lipids released from adipocytes Post lipase chemistry Carnitine mediated transport Beta-oxidation: the big picture Beta-oxidation:detailed chemistry Energy production from ox of palmitoyl CoA β-ox of oleic acid β-ox of poly unsaturates β-ox of odd numbered fatty acids Peroxisomes in eucaryotes Branched lipids can undergo α Oxidation Synthesis of ketone bodies Use of ketone bodies Ketone bodies in metabolism Chapter 19 The mitochondrion Electron carriers in ETS Overview of ETS ETS complex ETS complex ETS complex The Redox Table Redox example from complex Proton Motive Force The Chemiosmotic theory Some experimental support Motive force of NADH in the ETS The energetics of ATP synthesis The mechanism of ATP synthase ATP synthase in action A movie of the synthase from the side A movie of the synthase from the top A movie of the whole synthesis model Nucleotide translocation The glycerol phosphate shuttle for cytoplasmic NADH The malate-aspartate shuttle Thermogenin and heat Photosynthesis Our Friend, Mr Sun Photo pigments Harvesting the light spectrum Light harvesting machinery Exciton capture Bacterial photosystems are simple Structure of a bacterial photosystem The "Z" scheme of higher plants Membrane organization of PS Creating a proton gradient The Mn water splitter The energetics of photosynthesis Comparison of mitochondrion and chloroplasts The simplest light pump Photosynthesis - Dark Reacton Headlines Rubisco fixes CO2 The Calvin Cycle Giant Catabolic Roundup catabolic roundup The Cori Cycle Animals can synthesize glucose 6-phosphate via gluconeogenesis just like all other species However, unlike most species, animals can convert glucose 6-phosphate to glucose, which is secreted into the circulatory system Mammals, in particular, have a sophisticated cycle of secretion and uptake of glucose It's called the Cori cycle after the Nobel Laureates: Carl Ferdinand Cori and Gerty Theresa Cori The glucose 6-phosphate molecules synthesized in the liver can either be converted to glycogen [Glycogen Synthesis] or converted to glucose and secreted into the blood stream The glucose molecules are taken up by muscle cells where they can be stored as glucogen During strenuous exercise the glycogen is broken down to glucose 6-phosphate [Glycogen Degradation] and oxdized via the glycolysis pathway This pathway yields ATP that is used in muscle contraction If oxygen is limiting, the end product of glucose breakdown isn't CO2 but lactate Lactate is secreted into the blood stream where it is taken up by the liver and converted to pyruvate by the enzyme lactate dehydrogenase Pyruvate is the substrate for gluconeogenesis The synthesis of glucose in the liver requires energy in the form of ATP and this energy is supplied by a variety of sources The breakdown of fatty acids is the source shown in the figure The Cori cycle preserves carbon atoms The six carbon molecule, glucose, is split into two 3-carbon molecules (lactate) that are then converted to another 3-carbon molecule (pyruvate) Two pyruvates are joined to make glucose Production of biocellulose (bacterial cellulose) Biocellulose Cellulose is the main component of plant cell wall Some bacteria produce cellulose (celled biocellulose or bacterial cellulose) Plant cellulose and bacterial cellulose have the same chemical structure, but different physical and chemical properties Figure shows an electron microscopic image of biocellulose and plant cellulose Bacterial cellulose is produced by an acetic acid-producing bacterium, Acetobacter xylinum The diameter of biocellulose is about 1/100 of that of plant cellulose and Young's modulus of biocellulose is almost equivalent to that of aluminum Therefore, biocellulose is expected to be a new biodegradable biopolymer Fig Bacterial cellulose and plant cellulose Production of biocellulose in an airlift reactor In the mass production of biocellulose, conventionally an agitated reactor is used In our laboratory, we applied an airlift reactor to produce bacterial cellulose because this reactor is simple in structure, its energy requirement is low, its shear stress to cells is small, and the possibility of contamination is low Figure shows a 50-liter airlift reactor In the airlift reactor, the productivity of bacterial cellulose was equivalent to that in conventional agitated reactors and its energy requirement was one-tenth of that in agitated reactors The bacterial cellulose produced in an airlift reactor formed a unique pellet-type cellulose Fig 50 liter airlift reactor Analysis of genes for biocellulose synthesis All genes responsible for biocellulose synthesis have been cloned and their characterization is under way Figure shows the predicted steps of bacterial cellulose synthesis when glucose is used as the carbon source The analysis of genes will lead to higher productivity of bacterial cellulose and to new biocellulose with different properties Fig The predicted pathway of cellulose synthesis and secretion when glucose is taken into Gluconacetobactor xylinum from the outside of the cell Future aspects Preservation of forest resources is essential to prevent global warming because the increase in CO concentration can be stopped only by the absorption of CO2 by plants and trees However, the use of trees for the production of paper and construction materials has continuously depleated forest resources Bacterial cellulose is the only alternative for plant cellulose because bacteria produce bacterial cellulose in a few days, while trees need more than 30 years to realize full growth In this respect, bacterial cellulose is the key material for preventing global warming and preservation of the nature Metabolism of Major Non-Glucose Sugars Fructose Metabolism Diets containing large amounts of sucrose (a disaccharide of glucose and fructose) can utilize the fructose as a major source of energy The pathway to utilization of fructose differs in muscle and liver Muscle which contains only hexokinase can phosphorylate fructose to F6P which is a direct glycolytic intermediate In the liver which contains mostly glucokinase, which is specific for glucose as its substrate, requires the function of additional enzymes to utilize fructose in glycolysis Hepatic fructose is phosphorylated on C-1 by fructokinase yielding fructose-1-phosphate (F1P) In liver the form of aldolase that predominates (aldolase B) can utilize both F-1,6-BP and F1P as substrates Therefore, when presented with F1P the enzyme generates DHAP and glyceraldehyde The DHAP is converted, by triose phosphate isomerase, to G3P and enters glycolysis The glyceraldehyde can be phosphorylated to G3P by glyceraldehyde kinase or converted to DHAP through the concerted actions of alcohol dehydrogenase, glycerol kinase and glycerol phosphate dehydrogenase Three inherited abnormalities in fructose metabolism have been identified Essential fructosuria is a benign metabolic disorder caused by the lack of fructokinase which is normally present in the liver, pancreatic islets and kidney cortex The fructosuria of this disease depends on the time and amount of fructose and sucrose intake Since the disorder is asymptomatic and harmless it may go undiagnosed Hereditary fructose intolerance is a potentially lethal disorder resulting from a lack of aldolase B which is normally present in the liver, small intestine and kidney cortex The disorder is characterized by severe hypoglycemia and vomiting following fructose intake Prolonged intake of fructose by infants with this defect leads to vomiting, poor feeding, jaundice, hepatomegaly, hemorrhage and eventually hepatic failure and death The hypoglycemia that result following fructose uptake is caused by fructose-1-phosphate inhibition of glycogenolysis, by interfering with the phosphorylase reaction, and inhibition of gluconeogenesis at the deficient aldolase step Patients remain symptom free on a diet devoid of fructose and sucrose Hereditary fructose-1,6-bisphosphatase deficiency results in severely impaired hepatic gluconeogenesis and leads to episodes of hypoglycemia, apnea, hyperventillation, ketosis and lactic acidosis These symptoms can take on a lethal course in neonates Later in life episodes are triggered by fasting and febrile infections Clinical Significance of Fructose Metabolism Galactose Metabolism Galactose, which is metabolized from the milk sugar, lactose (a disaccharide of glucose and galactose), enters glycolysis by its conversion to glucose-1-phosphate (G1P) This occurs through a series of steps First the galactose is phosphorylated by galactokinase to yield galactose-1-phosphate Epimerization of galactose-1-phosphate to G1P requires the transfer of UDP from uridine diphosphoglucose (UDP-glucose) catalyzed by galactose-1phosphate uridyl transferase (official name: UDP-glucose hexose-1-phosphate uridylyltransferase) This generates UDP-galactose and G1P The UDP-galactose is epimerized to UDP-glucose by UDP-galactose-4 epimerase (see reaction mechanism) The UDP portion is exchanged for phosphate generating glucose-1-phosphate which then is converted to G6P by phosphoglucose mutase Galactose on the Web: Metabolic Pathways of Biochemistry: Galactose Pathway Clinical Significance of Galactose Metabolism Three inherited disorders of galactose metabolism have been delineated Classic galactosemia is a major symptom of two enzyme defects.One results from loss of the enzyme galactose-1phosphate uridyl transferase.The second form of galactosemia results from a loss of galactokinase These two defects are manifest by a failure of neonates to thrive Vomiting and diarrhea occur following ingestion of milk, hence individuals are termed lactose intolerant Clinical findings of these disorders include impaired liver function (which if left untreated leads to severe cirrhosis), elevated blood galactose, hypergalactosemia, hyperchloremic metabolic acidosis, urinary galactitol excretion and hyperaminoaciduria Unless controlled by exclusion of galactose from the diet, these galactosemias can go on to produce blindness and fatal liver damage Even on a galactose-restricted diet, transferase-deficient individuals exhibit urinary galacitol excretion and persistently elevated erythrocyte galactose-1-phosphate levels Blindness is due to the conversion of circulating galactose to the sugar alcohol galacitol, by an NADPH-dependent galactose reductase that is present in neural tissue and in the lens of the eye At normal circulating levels of galactose this enzyme activity causes no pathological effects However, a high concentration of galacitol in the lens causes osmotic swelling, with the resultant formation of cataracts and other symptoms The principal treatment of these disorders is to eliminate lactose from the diet The third disorder of galactose metabolism result from a deficiency of UDP-galactose-4epimerase Two different forms of this deficiency have been found One is benign affecting only red and white blood cells The other affects multiple tissues and manifests symptoms similar to the transferase deficiency Treatment involves restriction of dietary galactose Mannose Metabolism The digestion of many polysaccharides and glycoproteins yields mannose which is phosphorylated by hexokinase to generate mannose-6-phosphate Mannose-6-phosphate is converted to fructose-6-phosphate, by the enzyme phosphomannose isomerase, and then enters the glycolytic pathway or is converted to glucose-6-phosphate by the gluconeogenic pathway of hepatocytes In eukaryotes,mannose is constituent of N- and O-linked glycans as well as GPI anchors GDP-mannose is the donor form of mannose Glycerol Metabolism The predominant source of glycerol is adipose tissue This molecule is the backbone for the triacylglycerols Following release of the fatty acid portions of triacylglycerols the glycerol backbone is transported to the liver where it it phosphorylated by glycerol kinase yielding glycerol-3-phosphate Glycerol-3-phosphate is oxidized to DHAP by glycerol-3-phosphate dehydrogenase DHAP then enters the glycolytic if the liver cell needs energy However, the more likely fate of glycerol is to enter the gluconeogenesis pathway in order for the liver to produce glucose for use by the rest of the body Glucuronate Metabolism Glucuronate is a highly polar molecule which is incorporated into proteoglycans as well as combining with bilirubin and steroid hormones; it can also be combined with certain drugs to increase their solubility Glucuronate is derived from glucose in the uronic acid pathway The uronic acid pathway is utilized to synthesize UDP-glucuronate, glucuronate and Lascorbate The pathway involves the oxidation of glucosae-6-phosphate to UDP-glucuronate The oxidation is uncoupled from energy production UDP-glucuronate is used in the synthesis of glycosaminoglycan and proteoglycans as well as forming complexes with bilirubin, steroids and certain drugs The glucuronate complexes form to solubilize compounds for excretion The synthesis of ascorbate (vitamin C) does not occur in primates The uronic acid pathway is an alternative pathway for the oxidation of glucose that does not provide a means of producing ATP, but is utilized for the generation of the activated form of glucuronate, UDP-glucuronate The uronic acid pathway of glucose conversion to glucuronate begins by conversion of glucose-6-phosphate is to glucose-1-phosphate by phosphoglucomutase, and then activated to UDP-glucose by UDP-glucose pyrophosphorylase UDP-glucose is oxidized to UDP-glucuronate by the NAD +-requiring enzyme, UDP-glucose dehydrogenase UDP-glucuronate then serves as a precursor for the synthesis of iduronic acid and UDP-xylose and is incorporated into proteoglycans and glycoproteins or forms conjugates with bilirubin, steroids, xenobiotics, drugs and many compounds containing hydroxyl (-OH) groups Clinical Significance of Glucuronate In the adult human, a significant number of erythrocytes die each day This turnover releases significant amounts of the iron-free portion of heme, porphyrin, which is subsequently degraded The primary sites of porphyrin degradation are found in the reticuloendothelial cells of the liver, spleen and bone marrow The breakdown of porphyrin yields bilirubin, a product that is non-polar and therefore, insoluble In the liver, to which is transported in the plasma bound to albumin, bilirubin is solubilized by conjugation to glucuronate The soluble conjugated bilirubin diglucuronide is then secreted into the bile An inability to conjugate bilirubin, for instance in hepatic disease or when the level of bilirubin production exceeds the capacity of the liver, is a contributory cause of jaundice lipid : Classification and formation (Encyclopædia Britannica) There are four major classes of circulating lipoproteins, each with its own characteristic protein and lipid composition They are chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) Within all these classes of complexes, the Get full coverage on this topic and more with a FREE trial Ads by Google Chemical Synthesis Manufacture your product to your specs on time, cost-effectively www.RichmanChemical.com Phospholipids & Lecithin Soy, Egg, Synthetic & PEGylated cGMP Manufacturer: bulk quantities www.lipoid.com Peptide Synthesis Any scale, purity, full QC, fast delivery, great prices, world-wide www.proimmune.com CHAPTER - LIPID STRUCTURE A: Lipid Structure BIOCHEMISTRY - DR JAKUBOWSKI Learning Goals/Objectives for Chapter 1A: After class and this reading, students will be able to • • • draw line structures of fatty acids given their trivial and symbolic names and the reverse draw line structures of common phospholipids identify proR and pro S substituents on a a prochiral C center • explain the sn numbering systems for glycerophospholipids Saponifiable and Nonsaponifiable Lipids Lipids can be considered to be biological molecules which are soluble in organic solvents, such as chloroform/methanol, and are sparingly soluble in aqueous solutions There are two major classes, saponifiable and nonsaponifiable, based on their reactivity with strong bases The nonsaponifiable classes include the "fat-soluble" vitamins (A, E) and cholesterol Figure: Examples saponifiable and nonsaponifiable lipids Saponification is the process that produces soaps from the reaction of lipids and a strong base The saponifiable lipids contain long chain carboxylic acids, or fatty acids, esterified to a “backbone” molecule, which is either glycerol or sphingosine Note on nomenclature: Lipids are often distinguished from another commonly used word, fats Some define fats as lipids that contain fatty acid that are esterified to glycerol I will use the lipid and fat synonymously The major saponifiable lipids are triacylglycerides, glycerophospholipids, and the sphingolipids The first two use glycerol as the backbone Triacylglycerides have three fatty acids esterified to the three OHs on glycerol Glycerophospholipids have two fatty acids esterified at carbons and 2, and a phospho-X groups esterifed at C3 Spingosine, the backbone for spingolipids, has a long alkyl group connected at C1 and a free amine at C2, as a backbone In spingolipids, a fatty acid is attached through an amide link at C2, and a H or esterified phospho-X group is found at C3 A general diagrams showing the difference in these structures is shown below Figure: Classification of common phospholipids, glycolipids, and triacylglyerides The actual chemical structures of these lipids are shown below Figure: Structures of common phospholipids Figure: Comparison of lipids with glycerol and sphingosine as backbones Properties of Lipids The structure of these molecules determines their function For example, the very insoluble triacylglycerides are used as the predominant storage form of chemical energy in the body In contrast to polysaccharides such as glycogen (a polymer of glucose), the Cs in the acyl-chains of the triacylglyceride are in a highly reduced state The main source of energy to drive not only our bodies but also our society is obtained through oxidizing carbon-based molecules to carbon dioxide and water, in a reaction which is highly exergonic and exothermic Sugars are already part way down the free energy spectrum since each carbon is partially oxidized kcal/mol can be derived from the complete oxidation of fats, in contrast to 4.5 kcal/mol from that of proteins or carbohydrates In addition, glycogen is highly hydrated For every g of glycogen, grams of water is H-bonded to it Hence it would take times more weight to store the equivalent amount of energy in carbohydrates as is stored in triacylglyceride, which are stored in anhydrous lipid "drops" within cells The rest of this unit on lipids will focus not on triacylglycerides, whose main function is energy storage, but on fatty acids and phospholipids, and the structures they form in aqueous solution The structure of fatty acids and phospholipids show them to amphiphilic - i.e they have both hydrophobic and hydrophilic domains Fatty acids can be represented in "cartoon-form" as single chain amphiphiles with a circular polar head group and a single acyl non-polar tail extending from the head Likewise, phospholipids can be shown as double chain amphiphiles Even cholesterol can be represented this way, with its single OH group as the polar head, and the rigid member rings as the hydrophobic “tail” Even through there are a very large number of fatty acids which can be esterified to C1 and C2 of phospholipids and a variety of P-X groups at C3, making the phospholipids and fatty acids extremely heterogeneous groups of molecules, their role in biological structures can be understood quite simply by modeling them either as single or double chain amphiphiles This reduces their apparent complexity dramatically In addition, they, in contrast to carbohydrates, amino acids, and nucleotides, not form covalent polymers Hence we will start our studies of biological molecules with lipids (fatty acids and phospholipids) and then apply our understanding of this class of molecules to the more complex systems of biological polymers We will see that phospholipids and sphingolipids are essential components of membrane structure Cholesterol is also found in membranes and is a precursor of steroid hormones Fatty acid structure and conformation Fatty acids can be saturated (contain no double bonds in the acyl chain), or unsaturated (with either one -monounsaturated - or multiple - polyunsaturated - double bond(s)) The table below gives the names, in a variety of formats, of common fatty acids Table: Names and structures of the most common fatty acids COMMON BIOLOGICAL SATURATED FATTY ACIDS Symbol common name systematic name structure mp(C) 12:0 Lauric acid dodecanoic acid CH3(CH2)10COOH 44.2 14:0 Myristic acid tetradecanoic acid CH3(CH2)12COOH 52 16:0 Palmitic acid Hexadecanoic acid CH3(CH2)14COOH 63.1 18:0 Stearic acid Octadecanoic acid CH3(CH2)16COOH 69.6 20:0 Arachidic aicd Eicosanoic acid CH3(CH2)18COOH 75.4 COMMON BIOLOGICAL UNSATURATED FATTY ACIDS Symbol 16:1∆9 common name systematic name Palmitoleic acid Hexadecenoic acid structure mp(C) CH3(CH2)5CH=CH-(CH2)7COOH -0.5 18:1∆9 Oleic acid 9-Octadecenoic acid CH3(CH2)7CH=CH-(CH2)7COOH 13.4 18:2∆9,12 Linoleic acid 9,12 -Octadecadienoic acid CH3(CH2)4(CH=CHCH2)2(CH2)6COOH -9 18:3∆9,12,15 α−Linolenic acid 9,12,15 -Octadecatrienoic acid CH3CH2(CH=CHCH2)3(CH2)6COOH -17 20:4∆5,8,11,14 arachidonic acid 20:5∆5,8,11,14,17 EPA 5,8,11,14,17Eicosapentaenoicacid CH3CH2(CH=CHCH2)5(CH2)2COOH 22:6 ∆4,7,10,13,16,19 DHA Docosohexaenoic acid 22:6ω3 5,8,11,14CH3(CH2)4(CH=CHCH2)4(CH2)2COOH Eicosatetraenoic acid -49 -54 % FATTY ACIDS IN VARIOUS FATS FAT [...]... converted to glucose-1-phosphate by phosphoglucomutase and enters the "normal" glycolytic path This process is rather complex It involves exchanging a glucose-1-phosphate group in uridine diphosphate glucose (UDP-glucose) with galactose-1-P The resulting uridine diphosphate galactose (UDP-galactose) is then converted by an isomerase back to UDP-glucose Galactose is a good substrate for synthesis of glucose... essential that glucokinase does not become activated and transform glucose to G-6-P during this export process The balance between glucokinase and glucose-6-phosphatase slides back and forth, increasing uptake to the liver and phosphorylation when the level of blood glucose is high, and releasing glucose from G-6-P when blood glucose falls This is depicted in the next figure Control of glucose-6phosphatase... activates inward hepatic glucose transport and glucokinase activity Since glucokinase is not product-inhibited, the liver is able to take up and store large amounts of glucose as glycogen after a meal This can then be released to the circulation later to stabilize blood glucose levels Pancreatic ß-cells secrete insulin in response to very small increases in blood glucose concentration The glucose transport... linkages The simplest polysaccharide is a long chain (polymer) of glucose, called "starch" There are three types of starch: (1) Amylose: a non-branching straight chain of glucose - used to store glucose in plants (2) Amylopectin: a branched chain, also used to store glucose in plants (3) Glycogen: another branched chain molecule used to store glucose in animals Polysaccharides can also form very important... losing our appetite? Hepatic glucose release and glucokinase While glucokinase has a high Km (low affinity) for its substrate, it reacts strongly with glucose at the concentrations found in portal blood after a carbohydrate meal The Km of the liver enzyme, around 5-6 mmolar, lies above fasting blood glucose levels This means that glucokinase activity is "turned on " by the glucose in portal blood following... circulation and permits intestinal uptake of this sugar Glucose, the major dietary monosaccharide Starch is actually "poly-glucose" and its hydrolysis in the small intestine yields only glucose "Sugar", that is table sugar or sucrose, is 50 % glucose and 50 % fructose Lactose (milk sugar) and HFCS or high fructose corn syrup, also contain 50 % glucose Glucose is that monosaccharide upon which nature has... control has been well-documented previously with respect to the insulin-sensitive glucose carrier GLUT4 Fructose Metabolism and dyslipidemia Why is fructose such a strong signal for release of glucokinase Remember, glucokinase is "not interested" in reacting with fructose It is specific for glucose Starch, which yields glucose during digestion, has been a main energy source for mankind since the agricultural... competitive inhibitory action of glucose at normal blood glucose concentrations, hexokinase reacts only with glucose in the body's tissues Glucokinase is specific for glucose and does not catalyze reactions with other sugars Galactose, the "other half" of lactose (milk sugar) Galactose is transported from the intestinal lumen by the same Na+-dependent symport that is responsible for glucose transport It is... appetite control Glucose metabolism is initiated by either hexokinase or glucokinase The former is involved in energy metabolism in most tissues and is feed-back controlled That is, glucose transport into the cell and hexokinase activity rise and fall according to the use of its product, glucose-6-phosphate (G-6-P) Hexokinase has a low Km for glucose; it can be active at all normal blood glucose concentrations... is linked to storage of glucose as glycogen for later use in anaerobic and aerobic glycolysis In contrast to hexokinase, glucokinase has a Km of about 5 mmolar This is equivalent to normal blood glucose levels Glucokinase is found in just a few tissues, the liver, ß-cells in the pancreas and in the hypothalamus Uptake of glucose after a meal can increase the concentration of glucose in portal blood