Carbohydrate metabolism

Chapter 3(cont.)

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 cycleOxidative phosphorylation/ Electron

Transport Chain(ETC)

STARCHY FOOD

α – AMYLASE ; MALTASES

Glycolysis in cytosol

Brief overview of catabolism of glucose to generate energy

Glucose converted to glu-6-PO4

Start of cycle

2[Pyruvate+ATP+NADH]

- Krebs Cycle- E transport chain

Aerobic condition; in mitochondriaAnaerobic

condition

Lactic Acid fermentation in muscle.Only in yeast/bacteria Anaerobic respiration or Alcohol fermentation

Pyruvate enters as AcetylcoA

Glucose

Cycle : anaerobic

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

p.495

STEP 1

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

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?

as

Fig. 18-12, p.502

Controlling glucose metabolism• found in Cori cycle• shows the cycling of

glucose due to gycolysis in muscle and gluconeogenesis in liver

As energy store for next exercise

• 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

Cori cycle requires the net hydrolysis of two ATP and two GTP.

OHATPHNADHPyruvate

PADPNADeglu i

222422

222cos

iPGDPADPNADeGlu

OHGTPATPHNADHPyruvate

6242cos

624422 2

iPGDPADPOHGTPATP

422422 2

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

Fig. 19-2, p.513

Fig. 19-3b, p.514

Steps 3,4,6 and 8 – oxidation reactions

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

p.518

Step 1 Formation of citrate

Table 19-1, p.518

Step 2 Isomerization

Fig. 19-6, p.519

cis-Aconitate as an intermediate in the conversion of citrate to isocitrate

Fig. 19-7, p.521

Step 3

Formation of α-ketoglutarate and CO2 – first oxidation

p.521

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

p.522

Step 5 Formation of succinate

p.523a

Step 6

Formation of fumarate – FAD-linked oxidation

p.524a

Step 7 Formation of L-malate

p.524b

Step 8 Regeneration of oxaloacetate – final oxidation step

Fig. 19-8, p.526

Krebs cycle produced:• 6 CO2

• 2 ATP• 6 NADH• 2 FADH2

Table 19-3, p.527

Fig. 19-10, p.530

Fig. 19-11, p.531

Fig. 19-12, p.533

Fig. 19-15, p.535

Overall production from glycolysis, oxidative decarboxylation and TCA:

Oxidative decarboxylatio

n

Glycolysis TCA cycle

- 2 ATP 2 ATP

2 NADH 2 NADH 6 NADH , 2 FADH2

2 CO2 2 Pyruvate 4 CO2

Electron transportation system

Fig. 18-CO, p.487

Glycogen metabolism

Glycogen stored in muscle and liver cells.

Important in maintaining blood glucose levels.

Glycogen structure: α-1,4 glycosidic linkages with α-1,6 branches.

Branches give multiple free ends for quicker breakdown or for more places to add additional units.

Fig. 18-1, p.488

STEP 1

STEP 2

Glycogen phosphorylase

Phosphoglucomutase

Fig. 18-2, p.489

Glycogen Synthesis

• Not reverse of glycogen degradation because different enzymes are used.

• About 2/3 of glucose ingested during a meal is converted to glycogen.• First step is the first step of glycolysis:

hexokinaseglucose --------------> glucose 6-phosphate

• There are three enzyme-catalyzed reactions:

phosphoglucomutaseglucose 6-phosphate ---------------------> glucose 1-

phosphateglucose 1-phosphate ---------------> UDP-glucose (activated

form of glucose)glycogen synthase

UDP-glucose ----------------------> glycogen

• Glycogen synthase cannot initiate glycogen synthesis; requires preexisting primer of glycogen consisting of 4-8 glucose residues with a (1,4) linkage.

• Protein called glycogenin serves as anchor; also adds 7-8 glucose residues.

• Addition of branches by branching enzyme (amylo-(1,4 --> 1,6)-transglycosylase).

• Takes terminal 7 glucose residues from nonreducing end and attaches it via a(1,6) linkage at least 4 glucose units away from nearest branch.

p.490

Fig. 18-3, p.491

Fig. 18-4, p.492

REGULATION OF GLYCOGEN METABOLISM

Mobilization and synthesis of glycogen under hormonal control.

Three hormones involved:

1) Insulin• 51 a.a. protein made by b cells of pancreas.• Secreted when [glucose] high --> increases rate of glucose transport into muscle

and fat via GLUT4 glucose transporters.• Stimulates glycogen synthesis in liver.

2) Glucagon• 29 a.a. protein secreted by a cells of pancreas.• Operational under low [glucose].• Restores blood sugar levels by stimulating glycogen degradation.

3) Epinephrine• Stimulates glycogen mobilization to glucose 1-phosphate --> glucose 6-phosphate.• Increases rate of glycolysis in muscle and the amount of glucose in bloodstream.

Regulation of glycogen phosphorylase and glycogen synthase

• Reciprocal regulation.• Glycogen synthase -P --> inactive form (b).• Glycogen phosphorylase-P ---> active (a).

• When blood glucose is low, protein kinase A activated through hormonal action of glucagon --> glycogen synthase inactivated and phosphorylase kinase activated --> activates glycogen phosphorylase --> glycogen degradation occurs.

• Phosphorylase kinase also activated by increased [Ca2+] during muscle contraction.

• To reverse the same pathway involves protein phosphatases, which remove phosphate groups from proteins --> dephosphorylates phosphorylase kinase and glycogen phosphorylase (both inactivated), but dephosphorylation of glycogen synthase activates this enzyme.

• Protein phosphatase-1 activated by insulin --> dephosphorylates glycogen synthase --> glycogen synthesis occurs.

• In liver, glycogen phosphorylase a inhibits phosphatase-1 --> no glycogen synthesis can occur.

• Glucose binding to protein phosphatase-1 activated protein phosphatase-1 --> it dephosphorylates glycogen phosphorylase --> inactivated --> no glycogen degradation.

• Protein phosphatase-1 can also dephosphorylate glycogen synthase --> active.

p.493