Carbohydrate metabolism Chapter 3 Carbohydrate metabolism

Break-down of glucose to generate energy - Also known as Respiration. - Comprises of these different processes depending on type of organism: I. Anaerobic Respiration II. Aerobic Respiration

Anaerobic Respiration Comprises of these stages: glycolysis: glucose 2 pyruvate + NADH fermentation: pyruvate lactic acid or ethanol cellular respiration:

Aerobic Respiration Comprises of these stages: Oxidative decarboxylation of pyruvate Citric Acid cycle Oxidative phosphorylation/ Electron Transport Chain(ETC)

Brief overview of catabolism of glucose to generate energy STARCHY FOOD α – AMYLASE ; MALTASES Glucose Glucose converted to glu-6-PO4 Start of cycle Glycolysis in cytosol Cycle : anaerobic Aerobic condition; in mitochondria 2[Pyruvate+ATP+NADH] Anaerobic condition Pyruvate enters as AcetylcoA - Krebs Cycle - E transport chain Lactic Acid fermentation in muscle. Only in yeast/bacteria Anaerobic respiration or Alcohol fermentation

GLYCOLYSIS Show time..

Glycolysis 1st stage of glucose metabolism → glycolysis An anaerobic process, yields 2 ATP (additional energy source) Glucose will be metabolized via gycolysis; pyruvate as the end product The pyruvate will be converted to lactic acid (muscles → liver) Aerobic conditions: the main purpose is to feed pyruvate into TCA cycle for further rise of ATP

The breakdown of glucose to pyruvate as summarized: Glucose (six C atoms) → 2 pyruvate (three C atoms) 2 ATP + 4 ADP + 2 Pi → 2 ADP + 4 ATP (phosphorylation) Glucose + 2 ADP + 2 Pi → 2 Pyruvate + 2 ATP (Net reaction) FIGURE 17.1 One molecule of glucose is converted to two molecules of pyruvate. Under aerobic conditions, pyruvate is oxidized to CO2 and H2O by the citric acid cycle (Chapter 19) and oxidative phosphorylation (Chapter 20). Under anaerobic conditions, lactate is produced, especially in muscle. Alcoholic fermentation occurs in yeast. The NADH produced in the conversion of glucose to pyruvate is reoxidized to NAD+ in the subsequent reactions of pyruvate. Fig. 17-1, p.464

FIGURE 17.2 The glycolytic pathway. Fig. 17-2, p.465

Louis Pasteur French biologist did research on fermentation which led to important discoveries in microbiology and chemistry Louis Pasteur (1822–1895). His research on fermentation led to important discoveries in microbiology and chemistry.

How 6-carbon glucose converted to the 3-carbon glyceraldehyde-3-phosphate? Preparation phase Step 1 Glucose is phosphorylated to give gluc-6-phosphate p.467

FIGURE 17.3 In the first phase of glycolysis, five reactions convert a molecule of glucose to two molecules of glyceraldehyde-3-phosphate. Fig. 17-3, p.468

FIGURE 17.3 In the first phase of glycolysis, five reactions convert a molecule of glucose to two molecules of glyceraldehyde-3-phosphate.

Table 17-1, p.469

FIGURE 17.4 A comparison of the conformations of hexokinase and the hexokinase–glucose complex. Fig. 17-4, p.470

Glucose-6-phosphate isomerize to give fructose-6-phosphate Step 2 p.470a

Step 3 Fructose-6-phosphate is phosphorylated producing fructose-1,6-bisphosphate p.470b

FIGURE 17.6 At high [ATP], phosphofructokinase behaves cooperatively, and the plot of enzyme activity versus [fructose-6-phosphate] is sigmoidal. High [ATP] thus inhibits PFK, decreasing the enzyme’s affinity for fructose-6-phosphate. Fig. 17-6, p.471

Fructose-1,6-bisphosphate split into two 3-carbon fragments Step 4 Fructose-1,6-bisphosphate split into two 3-carbon fragments p.471a

Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate Step 5 Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate p.471b

How is glyceraldehyde-6-phosphate converted to pyruvate Payoff phase Step 6 Glyceraldehyde-6-phosphate is oxidized to 1,3-bisphosphoglycerate p.472

FIGURE 17.7 The second phase of glycolysis. Fig. 17-7, p.473

FIGURE 17.7 The second phase of glycolysis.

p.474a

FIGURE 17.8 Schematic view of the binding site of an NADH-linked dehydrogenase. There are specific binding sites for the adenine nucleotide portion of the coenzyme (shown in red to the right of the dashed line) and for the nicotinamide portion of the coenzyme (shown in yellow to the left of the dashed line), in addition to the binding site for the substrate. Specific interactions with the enzyme hold the substrate and coenzyme in the proper positions. Sites of interaction are shown as a series of pale green lines. Fig. 17-8, p.475

Production of ATP by phosphorylation of ADP Step 7 Production of ATP by phosphorylation of ADP p.476

Phosphate group is transferred from C-3 to C-2 Step 8 Phosphate group is transferred from C-3 to C-2 p.477a

Dehydration reaction of 2-phosphoglycerate to phosphoenolpyruvate Step 9 Dehydration reaction of 2-phosphoglycerate to phosphoenolpyruvate p.477b

Step 10 Phosphoenolpyruvate transfers its phosphate group to ADP → ATP and pyruvate p.478

Control points in glycolysis FIGURE 17.10 Control points in glycolysis. Control points in glycolysis Fig. 17-10, p.479

How is pyruvate metabolized anaerobically? Conversion of pyruvate to lactate in muscle p.479

FIGURE 17.11 The recycling of NAD and NADH in anaerobic glycolysis. Fig. 17-11b, p.481

FIGURE 17.11 The recycling of NAD and NADH in anaerobic glycolysis. Pyruvate decarboxylase Fig. 17-11a, p.481

FIGURE 17.12 The structures of thiamine (vitamin B1) and thiamine pyrophosphate (TPP), the active form of the coenzyme. Fig. 17-12, p.482

Acetaldehyde + NADH → Ethanol + NAD+ Glucose + 2 ADP + 2 Pi + 2 H+ → 2 Ethanol + 2 ATP + 2 CO2 + 2 H2O p.482

Carbohydrate metabolism Chapter 3 (cont.) Carbohydrate metabolism

Gluconeogenesis Conversion of pyruvate to glucose Biosynthesis and the degradation of many important biomolecules follow different pathways There are three irreversible steps in glycolysis and the differences bet. glycolysis and gluconeogenesis are found in these reactions Different pathway, reactions and enzyme STEP 1 p.495

is the biosynthesis of new glucose from non-CHO precursors. this glucose is as a fuel source by the brain, testes, erythrocytes and kidney medulla comprises of 9 steps and occurs in liver and kidney the process occurs when quantity of glycogen have been depleted - Used to maintain blood glucose levels. Designed to make sure blood glucose levels are high enough to meet the demands of brain and muscle (cannot do gluconeogenesis). promotes by low blood glucose level and high ATP inhibits by low ATP occurs when [glu] is low or during periods of fasting/starvation, or intense exercise pathway is highly endergonic *endergonic is energy consuming

FIGURE 18. 6 The pathways of gluconeogenesis and glycolysis FIGURE 18.6 The pathways of gluconeogenesis and glycolysis. Species in blue, green, and pink shaded boxes indicate other entry points for gluconeogenesis (in addition to pyruvate). STEP 2

The oxalocetate formed in the mitochondria have two fates: - continue to form PEP - turned into malate by malate dehydrogenase and leave the mitochondria, have a reaction reverse by cytosolic malate dehydrogenase Reason? FIGURE 18.9 Pyruvate carboxylase catalyzes a compartmentalized reaction. Pyruvate is converted to oxaloacetate in the mitochondria. Because oxaloacetate cannot be transported across the mitochondrial membrane, it must be reduced to malate, transported to the cytosol, and then oxidized back to oxaloacetate before gluconeogenesis can continue.

as Controlling glucose metabolism found in Cori cycle shows the cycling of glucose due to gycolysis in muscle and gluconeogenesis in liver This two metabolic pathways are not active simultaneously. when the cell needs ATP, glycolisys is more active When there is little need for ATP, gluconeogenesis is more active As energy store for next exercise FIGURE 18.12 The Cori cycle. Lactate produced in muscles by glycolysis is transported by the blood to the liver. Gluconeogenesis in the liver converts the lactate back to glucose, which can be carried back to the muscles by the blood. Glucose can be stored as glycogen until it is degraded by glycogenolysis. (NTP stands for nucleoside triphosphate.) Fig. 18-12, p.502

Cori cycle requires the net hydrolysis of two ATP and two GTP. Gerty and Carl Cori, codiscoverers of the Cori cycle.

FIGURE 18. 13 Control of liver pyruvate kinase by phosphorylation FIGURE 18.13 Control of liver pyruvate kinase by phosphorylation. When blood glucose is low, phosphorylation of pyruvate kinase is favored. The phosphorylated form is less active, thereby slowing glycolysis and allowing pyruvate to produce glucose by gluconeogenesis. Fig. 18-13, p.503

The Citric Acid cycle Cycle where 30 to 32 molecules of ATP can be produced from glucose in complete aerobic oxidation Amphibolic – play roles in both catabolism and anabolism The other name of citric acid cycle: Krebs cycle and tricarboxylic acid cycle (TCA) Takes place in mitochondria FIGURE 19.1 The central relationship of the citric acid cycle to catabolism. Amino acids, fatty acids, and glucose can all produce acetyl-CoA in stage 1 of catabolism. In stage 2, acetyl-CoA enters the citric acid cycle. Stages 1 and 2 produce reduced electron carriers (shown here as e-). In stage 3, the electrons enter the electron transport chain, which then produces ATP.

FIGURE 19. 2 The structure of a mitochondrion FIGURE 19.2 The structure of a mitochondrion. (a) Colored scanning electron microscope image showing the internal structure of a mitochondrion (green, magnified 19,200 x). (b) Interpretive drawing of the scanned image. (c) Perspective drawing of a mitochondrion. (For an electron micrograph of mitochondrial structure, see Figure 1.13.) Fig. 19-2, p.513

FIGURE 19. 3 An overview of the citric acid cycle FIGURE 19.3 An overview of the citric acid cycle. Note the names of the enzymes. The loss of CO2 is indicated, as is the phosphorylation of GDP to GTP. The production of NADH and FADH2 is also indicated.

Steps 3,4,6 and 8 – oxidation reactions FIGURE 19.3 An overview of the citric acid cycle. Note the names of the enzymes. The loss of CO2 is indicated, as is the phosphorylation of GDP to GTP. The production of NADH and FADH2 is also indicated. Fig. 19-3b, p.514

5 enzymes make up the pyruvate dehydrogenase complex: pyruvate dehydrogenase (PDH) Dihydrolipoyl transacetylase Dihydrolipoyl dehydrogenase Pyruvate dehydrogenase kinase Pyruvate dehydrogenase phosphatase Conversion of pyruvate to acetyl-CoA

Step 1 Formation of citrate p.518

Step 2 Isomerization Table 19-1, p.518

cis-Aconitate as an intermediate in the conversion of citrate to isocitrate FIGURE 19.6 Three-point attachment to the enzyme aconitase makes the two -CH2-COO- ends of citrate stereochemically nonequivalent. Fig. 19-6, p.519

Formation of α-ketoglutarate and CO2 – first oxidation Step 3 Formation of α-ketoglutarate and CO2 – first oxidation FIGURE 19.7 The isocitrate dehydrogenase reaction. Fig. 19-7, p.521

Formation of succinyl-CoA and CO2 – 2nd oxidation Step 4 Formation of succinyl-CoA and CO2 – 2nd oxidation p.521

Formation of succinate Step 5 Formation of succinate p.522

Formation of fumarate – FAD-linked oxidation Step 6 Formation of fumarate – FAD-linked oxidation p.523a

Step 7 Formation of L-malate p.524a

Regeneration of oxaloacetate – final oxidation step Step 8 p.524b

Krebs cycle produced: 6 CO2 2 ATP 6 NADH 2 FADH2 Fig. 19-8, p.526 FIGURE 19.8 Control points in the conversion of pyruvate to acetyl-CoA and in the citric acid cycle. Krebs cycle produced: 6 CO2 2 ATP 6 NADH 2 FADH2 Fig. 19-8, p.526

Table 19-3, p.527

FIGURE 19.10 A summary of catabolism, showing the central role of the citric acid cycle. Note that the end products of the catabolism of carbohydrates, lipids, and amino acids all appear. (PEP is phosphoenolpyruvate; -KG is  ketoglutarate; TA is transamination;  is a multistep pathway.) Fig. 19-10, p.530

FIGURE 19.11 How mammals keep an adequate supply of metabolic intermediates. An anabolic reaction uses a citric acid cycle intermediate (- ketoglutarate is transaminated to glutamate in our example), competing with the rest of the cycle. The concentration of acetyl-CoA rises and signals the allosteric activation of pyruvate carboxylase to produce more oxaloacetate. * Anaplerotic reaction. **Part of glyoxylate pathway. Fig. 19-11, p.531

FIGURE 19.12 Transfer of the starting materials of gluconeogenesis from the mitochondrion to the cytosol. Note that phosphoenolpyruvate (PEP) can be transferred from the mitochondrion to the cytosol, as can malate. Oxaloacetate is not transported across the mitochondrial membrane. (1 is PEP carboxykinase in mitochondria; 2 is PEP carboxykinase in cytosol; other symbols are as in Figure 19.10.) Fig. 19-12, p.533

FIGURE 19.15 A summary of anabolism, showing the central role of the citric acid cycle. Note that there are pathways for the biosynthesis of carbohydrates, lipids, and amino acids. OAA is oxaloacetate, and ALA is -aminolevulinic acid. Symbols are as in Figure 19.10.) Fig. 19-15, p.535

Oxidative decarboxylation Overall production from glycolysis, oxidative decarboxylation and TCA: Oxidative decarboxylation Glycolysis TCA cycle - 2 ATP 2 NADH 6 NADH , 2 FADH2 2 CO2 2 Pyruvate 4 CO2 Electron transportation system