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Carbohydrate Energetics

SUDHANSHU RAMANFNT-PA5-03

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Fates of Catabolized Organic Nutrients

• Energy (ATP)• Raw materials used in anabolism • Structural proteins• Enzymes• Lipid storage• Glycogen storage

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Glucose• Glucose is the molecule ultimately used by body cells to

make ATP.• Neurons and RBCs rely almost entirely upon glucose to

fullfill their energy needs.• Excess glucose is converted to glycogen or fat and stored.

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Figure 25–1

Cellular Metabolism

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Nutrient Use in Cellular Metabolism

Figure 25–2 (Navigator)

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Synthesis of New Organic Compounds

• In energy terms, anabolism is an “uphill” process that forms new chemical bonds while catabolism is a downhill process that provides energy by breaking chemical bonds• Building new organic compounds requires both energy

(garnered from earlier catabolism) and raw materials.

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Organic Compounds• Glycogen:• a branched chain of glucose molecules• most abundant storage carbohydrate

• Triglycerides:• most abundant storage lipids• Energy is primarily stored in the fatty acids

• Proteins:• most abundant organic components in body• perform many vital cellular functions

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Energy Extraction• C-H bonds store the most energy• C-C also store a lot of energy• C-O bonds store very little energy

Macromolecules that we take in via our diet are mostly rich in C-H and C-C bonds. In the body, these are broken down and turned into C-O bonds that are then breathed out as carbon dioxide.• In the process, some of the energy released by breaking those

bonds is captured to make ATP

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Carbohydrate Metabolism • Generates ATP and other high-energy compounds by breaking

down carbohydrates:glucose + oxygen carbon dioxide + water

• Occurs in small steps which release energy to convert ADP to ATP• Involves glycolysis, TCA cycle, and electron transport• 1 molecule of glucose nets 36* molecules of ATP

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Glycolysis • Breaks down glucose in cytosol into smaller molecules used by mitochondria .• Does not require oxygen so it is anaerobic.• 1 molecule of glucose yields only 2 ATP.• Yields very little energy on its own, but it is enough to power

muscles for short periods .• Some bacteria are entirely anaerobic and survive by performing

only glycolysis.• RBCs and working muscle tissue use glycolysis as their primary source of ATP.

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Aerobic / Cellular Respiration Reactions

• Include the TCA cycle and electron transport.• Occur in mitochondria:• consume oxygen • produce lots of ATP• Much more efficient

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Overview – Aerobic metabolism• Glycolysis:• breaks 6-carbon glucose into two 3-carbon pyruvic acid .

• TCA cycle • 3 carbon pyruvate is adapted into 2 carbon acetyl CoA

(probably the most important, most central molecule in metabolism)• Acetyl CoA is conveted into carbon dioxide and the

energy is captured in an intermediate called NADH• Electron Transport• Uses oxidative phosphorylation to turn NADH into ATP• requires oxygen and electrons; thus the rate of ATP

generation is limited by oxygen or electrons

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ATP Production• For 1 glucose molecule processed, cell gains 36 molecules of

ATP:• 2 from glycolysis• 4 from NADH generated in glycolysis (requires oxygen)• 2 from TCA cycle (through GTP)• 28 from electron transport

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Energy Yield of Aerobic Metabolism

Figure 25–6

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Glycolysis

Triose phosphate isomerase

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Importance of Phosphorylated Intermediates

1. Because the plasma membrane generally lacks transporters for phosphorylated sugars, the phosphorylated glycolytic intermediates cannot leave the cell.

• After the initial phosphorylation, no further energy is necessary to retain phosphorylated intermediates in the cell, despite the large difference in their intracellular and extracellular concentrations.

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• 2. Phosphoryl groups are essential components in the enzymatic conservation of metabolic energy. Energy released in the breakage of phosphoanhydride bonds (such as those in ATP) is partially conserved in the formation of phosphate esters such as glucose 6-phosphate.

• High-energy phosphate compounds formed in glycolysis (1,3-bisphosphoglycerate and phosphoenolpyruvate) donate phosphoryl groups to ADP to form ATP.

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• 3. Binding energy resulting from the binding of phosphate groups to the active sites of enzymes lowers the activation energy and increases the specificity of the enzymatic reactions.

• The phosphate groups of ADP, ATP, and the glycolytic intermediates form complexes with Mg2, and the substrate binding sites of many glycolytic enzymes are specific for these Mg2 complexes. Most glycolytic enzymes require Mg2 for activity.

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Fate of Pyruvate

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Entry Into The Citric Acid Cycle

Glycolysis releases relatively little of the energy present in a glucose molecule; much more is released by the subsequent operation of the citric acid cycle and oxidative phosphorylation. Following this route under aerobic conditions, pyruvate is converted to acetyl CoA by the enzyme pyruvate dehydrogenase and the acetyl CoA then enters the citric acid cycle. The pyruvate dehydrogenase reaction is an oxidative decarboxylation

Pyruvate dehydrogenasepyruvate + NAD+ + CoA→ acetyl CoA + CO2 + NADH

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Conversion to fatty acid or ketone bodies.• When the cellular energy level is high (ATP in

excess), the rate of the citric acid cycle decreases and acetyl CoA begins to accumulate.

• Under these conditions, acetyl CoA can be used for fatty acid synthesis or the synthesis of ketone bodies

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Conversion to Lactate• The NAD+ used during glycolysis (in the formation of 1,3-

bisphosphoglycerate by glyceraldehyde 3-phosphate dehydrogenase); must be regenerated if glycolysis is to continue.

• Under aerobic conditions, NAD+ is regenerated by the re-oxidation of NADH via the electron transport chain.

• When oxygen is limiting, as in muscle during vigorous contraction, the re-oxidation of NADH to NAD+ by the electron transport chain becomes insufficient to maintain glycolysis.

• Under these conditions, NAD+ is regenerated instead by conversion of the pyruvate to lactate by lactate dehydrogenase:

Lactate dehydrogenasepyruvate + NADH + H+ lactate + NAD+

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Conversion to ethanol.• In yeast and some other microorganisms under anaerobic conditions, the

NAD+ required for the continuation of glycolysis & is regenerated by a process called alcoholic fermentation.

• The pyruvate is converted to acetaldehyde (by pyruvate decarboxylase) and then to ethanol (by alcohol dehydrogenase), the latter reaction reoxidizing the NADH to NAD+:

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Metabolism of FructoseThere are two pathways for the metabolism of fructose, one occurs in muscle and adipose tissue, the other in liver :-

1. In muscle and adipose tissue, fructose can be phosphorylated by hexokinase (which is capable of phosphorylating both glucose and fructose) to form fructose 6-phosphate which then enters glycolysis.

2. In liver, the cells contain mainly glucokinase instead of hexokinase and this enzyme phosphorylates only glucose. Thus in liver, fructose is metabolized instead by the fructose 1-phosphate pathway

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Metabolism of Galactose• The hydrolysis of the disaccharide lactose (in milk) yields galactose and

glucose.• Thus galactose is also a major dietary sugar for humans. Galactose and

glucose are epimers that differ in their configuration at C-4. Thus the entry of galactose into glycolysis requires an epimerization reaction.

• This occurs via a four-step pathway called the galactose–glucose interconversion pathway

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NEXT CITRIC ACID CYCLE

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• In the second stage the acetyl groups are fed into the citric acid cycle, which enzymatically oxidizes them to CO2; the energy released is conserved in the reduced electron carriers NADH and FADH2.

• In the third stage of respiration, these reduced coenzymes are themselves oxidized, giving up protons (H) and electrons.

• The electrons are transferred to O2—the final electron acceptor—via a chain of electron-carrying molecules known as the respiratory chain.

• In the course of electron transfer, the large amount of energy released is conserved in the form of ATP, by a process called oxidative phosphorylation

CITRIC ACID CYCLE

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“If citrate is added the rate of respiration is often increased . . . the extra oxygen uptake is by far greater than can be accounted for by the complete oxidation of citrate . . . Since citric acid reacts catalytically in the tissue it is probable that it is removed by a primary reaction but regenerated by a subsequent reaction.”

—H. A. Krebs and W. A. Johnson, article in Enzymologia, 1937

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Catabolism of proteins, fats, and carbohydrates in thethree stages of cellular respiration.

Stage 1: oxidation of fatty acids, glucose, and some amino acids yields acetyl-CoA.

Stage 2: oxidation of acetyl groups in the citric acid cycle includes four steps in which electrons are abstracted.

Stage 3: electrons carried by NADH and FADH2 are funneled into a chain of mitochondrial (or, in bacteria, plasma membrane–bound) electron carriers—the respiratory chain—ultimately reducing O2 to H2O. This electron flow drives the production of ATP.

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Breakdown of Pyruvate:

• Each pyruvate molecule loses a carboxylic group in the form of carbon dioxide.

• The remaining two carbons are then transferred to the enzyme CoA to produce Acetyl CoA.

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THREE DIMENSIONALimage of PDH complex, showing the subunit structure:

E1, pyruvate dehydrogenase;

E3,dihydrolipoyl dehydrogenase

E2, dihydrolipoyl transacetylase; .

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ELECTRON TRANSPORT AND OXIDATIVE PHOSPHORYLATION

• Electron transport and oxidative phosphorylation re-oxidize NADH and FADH2 and trap the energy released as ATP.

• In eukaryotes, electron transport and oxidative phosphorylation occur in the inner membrane of mitochondria whereas in prokaryotes the process occurs in the plasma membrane.

ATP synthase

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Cytochrome oxidase 4 cyt. c (Fe2+) + 4 H+ + O2 → 4 cyt. c (Fe3+) + 2 H2O

The cytochrome oxidase reaction is complex; it transfers four electrons from four cytochrome c molecules and four H+ ions to molecular oxygen to form two molecules of water

Inter membrane space

1 NADH->3ATP;FADH2->2ATP

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