Carbohydrate Metabolism

Carbohydrate  Metabolism An Overview

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General Biochemistry-II (BCH 302 Dr . Saba Abdi Asst . Prof. Dept. Of Biochemistry College Of Science King Saud University. Riyadh.KSA

Major Pathways

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3.

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Glycolysis Citric acid cycle 2. Gluconeogenesis Glycogen metabolism a( Glycogenesis )b( Glycogenolysis

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I. Glycolysis (Embden Meyerhof

Pathway):

A. Definition:          1. Glycolysis means oxidation of glucose to give pyruvate (in the

B. Site:           cytoplasm of all tissue cells, but it is of physiological importance in:

presence of oxygen) or lactate (in the absence of oxygen).

1. Tissues with no mitochondria: mature RBCs, cornea and lens.

2. Tissues with few mitochondria: Testis, leucocytes, medulla of the

kidney, retina, skin and gastrointestinal tract.

3. Tissues undergo frequent oxygen lack: skeletal muscles especially

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during exercise.

C. Steps:  Stages of glycolysis     1. Stage one (the energy requiring stage):         a) One molecule of glucose is converted into two molecules of

glycerosldhyde­3­phosphate.

b) These steps requires 2 molecules of ATP (energy loss)

2. Stage two (the energy producing stage(:         a) The 2 molecules of glyceroaldehyde­3­phosphate are converted into

pyruvate (aerobic glycolysis) or lactate (anaerobic glycolysis(.

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b) These steps produce ATP molecules (energy production).

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) Energy Investment Phase (steps 1-5

Fig. 9.9a

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Fig. 9.9b

) Energy-Payoff Phase (Steps 6-10

Energy production of glycolysis:

ATP produced

ATP utilized

Net energy

2 ATP

In absence of oxygen  (anaerobic glycolysis)

2ATP From glucose to  glucose ­6­p. From fructose ­6­p to  fructose 1,6 p.

6 ATP Or 8 ATP

In presence of  oxygen (aerobic  glycolysis)

2ATP ­From glucose to  glucose ­6­p. From fructose ­6­p to  fructose 1,6 p.

4 ATP  (Substrate level  phosphorylation)  2ATP from 1,3 DPG. 2ATP from  phosphoenol  pyruvate 4 ATP  (substrate level  phosphorylation)  2ATP from 1,3 BPG. 2ATP from  phosphoenol  pyruvate. + 4ATP or 6ATP (from oxidation of 2  NADH + H in  mitochondria).

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E. oxidation of extramitochondrial NADH+H+:      1. cytoplasmic NADH+H+ cannot penetrate mitochondrial membrane,          however, it can be used to produce energy (4 or 6 ATP) by respiratory          chain phosphorylation in the mitochondria.     2. This can be done by using special carriers for hydrogen of NADH+H+          These carriers are either dihydroxyacetone phosphate (Glycerophosphate           shuttle) or oxaloacetate (aspartate malate shuttle).          a) Glycerophosphate shuttle:              1) It is important in certain muscle and nerve cells.              2) The final energy produced is 4 ATP.              3) Mechanism:

­ The coenzyme of cytoplasmic glycerol­3­ phosphate dehydrogenase

is NAD+.

­ The coenzyme of mitochodrial glycerol­3­phosphate dehydogenase is     FAD. ­ Oxidation of FADH, in respiratory chain gives 2 ATP. As glycolysis     gives 2 cytoplasmic NADH + H+ (cid:0)  2 mitochondrial FADH,  2 x 2

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= 4 ATP.

ATP  (cid:0)          b) Malate – aspartate shuttle:                  1) It is important in other tissues patriculary liver and heart.                  2) The final energy produced is 6 ATP.

Differences between aerobic and anaerobic glycolysis:

Aerobic Anaerobic

1. End product Pyruvate Lactate

2 .energy 6 or 8 ATP 2 ATP

3. Regeneration of Through Lactate

NAD+ Through respiration  chain in mitochondria formation

4. Availability to TCA

in mitochondria Not available as lactate  is cytoplasmic substrate

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Available and 2   Pyruvate can  oxidize to  give 30  ATP

Importance of lactate production in anerobic

glycolysis:

1. In absence of oxygen, lactate is the end product of glycolysis:  Pyruvate (cid:0)

Glucose (cid:0)

Lactate

2. In absence of oxygen, NADH + H+ is not oxidized by the

respiratory chain.

3. The conversion of pyruvate to lactate is the mechanism for

regeneration of NAD+.

4. This helps continuity of glycolysis, as the generated NAD+ will be

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used once more for oxidation of another glucose molecule.

Substrate level phosphorylation:        This means phosphorylation of ADP to ATP at the reaction itself .in

glycolysis there are 2 examples:

­ 1.3 Bisphosphoglycerate + ADP  3 Phosphoglycerate + ATP

­ Phospho­enol pyruvate + ADP  Enolpyruvate + ATP I. Special features of glycolysis in RBCs:     1. Mature RBCs contain no mitochondria, thus:

a) They depend only upon glycolysis for energy production (=2 ATP).

b) Lactate is always the end product.

2. Glucose uptake by RBCs is independent on insulin hormone.

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3. Reduction of met­hemoglobin: Glycolysis produces NADH+H+, which          used for reduction of met­hemoglobin in red cells.

Biological importance (functions) of glycolysis:      1. Energy production:           a) anaerobic glycolysis gives 2 ATP.           b) aerobic glycolysis gives 8 ATP.     2. Oxygenation of tissues:        Through formation of 2,3 bisphosphoglycerate, which decreases the         affinity of Hemoglobin to O2.     3. Provides important intermediates:         a) Dihydroxyacetone phosphate: can give glycerol­3phosphate, which is               used for synthesis of triacylglycerols and phospholipids (lipogenesis).         b) 3 Phosphoglycerate: which can be used for synthesis of amino acid               serine.         c) Pyruvate: which can be used in synthesis of amino acid alanine.    4. Aerobic glycolysis provides the mitochondria with pyruvate, which gives          acetyl CoA    Krebs' cycle.

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Reversibility of glycolysis (Gluconeoqenesis):      1. Reversible reaction means that the same enzyme can catalyzes the

reaction in both directions.

2. all reactions of glycolysis ­except 3­ are reversible.

3. The 3 irreversible reactions (those catalyzed by kinase enzymes) can be

reversed by using other enzymes.

(cid:0) Glucose­6­p Glucose

F1, 6 Bisphosphate Fructose­6­p

(cid:0)  (cid:0) Pyruvate Phosphoenol pyruvate

4. During fasting, glycolysis is reversed for synthesis of glucose from non­

carbohydrate sources e.g. lactate. This mechanism is called:

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gluconeogenesis.

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• As pyruvate enters the mitochondrion, a multienzyme complex modifies pyruvate to acetyl CoA which enters the Krebs cycle in the . matrix A carboxyl group is removed as CO2 . A pair of electrons is transferred from the remaining two-carbon fragment to NAD+ to . form NADH

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The oxidized fragment, acetate, combines with coenzyme A to form acetyl CoA

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Fig. 9.10

Kreb Cycle

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Electron Transport Chain

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Summary

Mitochondrion

Electrons carried in NADH

Pyruvic acid

Electrons carried in NADH and FADH2

Glucose

Electron Transport Chain

Glycolysis

Krebs Cycle

Mitochondrion

Cytoplasm

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Total energy yield

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Glycolysis 2 ATP Krebs Cycle 2 ATP ETC  32 ATP

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Total 36 ATP

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Glycogen Metabolism

Py r o p h o s ph at as e

2  Pi

PPi

UDP­ Gluc o s e

Gly c og e n  (Gluc os e ) n

UT P

UDP­ Glu c o s e Py r o ph os ph or y las e

Glyc o g e n S y n t h a s e

UDP

G luc o s e ­ 6 ­ P

Gluc o s e ­ 1 ­ P

Gly c og e n  (G luc o s e ) n+1

Ph o s p h o g luc o m u t as e

Glyc og e n Ph os ph or ylas e

Gly c o ge n

Pi

( Gluc o s e ) n

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: Glycogenesis

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Glycogenesis is the formation of glycogen from glucose. Glycogen is synthesized depending on the demand for glucose and ATP )energy(. If both are present in relatively high amounts, then the excess of insulin promotes the glucose conversion into glycogen for storage in liver and muscle cells . In the synthesis of glycogen, one ATP is required per glucose incorporated into the polymeric branched structure of glycogen. actually, glucose-6-phosphate is the cross-roads compound. Glucose-6-phosphate is synthesized directly from glucose or as the end product . of gluconeogenesis

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Glycogenolysis

glycogenesis

In glycogenolysis, glycogen stored in the liver and muscles, is converted first to glucose-1- phosphate and then into glucose-6-phosphate. Two hormones which control glycogenolysis are a peptide, glucagon from the . pancreas and epinephrine from the adrenal glands Glucagon is released from the pancreas in response to low blood glucose and epinephrine is released in response to a threat or stress. Both hormones act upon enzymes to stimulate glycogen phosphorylase to begin glycogenolysis and inhibit glycogen synthetase )to stop (. 21

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.

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Glycogen is a highly branched polymeric structure containing glucose as the basic monomer. First individual glucose molecules are hydrolyzed from the chain, followed by the addition of a phosphate group at C-1. In the next step the phosphate is moved to the C-6 position to give glucose 6-phosphate, a cross road . compound Glucose-6-phosphate is the first step of the glycolysis pathway if glycogen is the carbohydrate source and further energy is needed. If energy is not immediately needed, the glucose-6-phosphate is converted to glucose for distribution in the blood to various cells such as Saba Abdi . 22

brain cells