Chapter 13. Glucose metabolism

Glucose

The primary sugar derived from the human diet and the preferred energy source for most cells tissues and organs

Importance of stable blood glucose

Maintains a continuous energy supply supports brain function and cognition and prevents energy spikes and crashes

Hypoglycemia

Abnormally low blood glucose generally below 70 mg per dL that can cause dizziness confusion fainting and potentially coma

Hyperglycemia

Abnormally high blood glucose that can damage blood vessels and organs over time and increase the risk of heart disease stroke vision loss and kidney failure

Glucose pathways

Interconnected biochemical routes used by cells to break down store or transform glucose to produce energy and biosynthetic building blocks

Catabolism

Metabolic processes that break down molecules to release energy and generate products such as ATP

Anabolism

Metabolic processes that build complex molecules from simpler precursors and generally require energy

Glycolysis

The pathway that breaks one glucose molecule into two pyruvate molecules while producing ATP and NADH

Gluconeogenesis

The synthesis of glucose from noncarbohydrate precursors such as lactate pyruvate glycerol and glucogenic amino acids

Glycogenesis

The process of converting glucose into glycogen for energy storage

Glycogenolysis

The breakdown of stored glycogen to release glucose units when energy or blood glucose is needed

Pentose phosphate pathway

An alternative pathway of glucose oxidation that generates NADPH and ribose 5 phosphate for biosynthesis and nucleotide synthesis

Ribose 5 phosphate

A five carbon sugar produced by the pentose phosphate pathway that serves as a precursor for nucleotide synthesis

Main glucose metabolic pathways

Glycolysis gluconeogenesis glycogenesis glycogenolysis and the pentose phosphate pathway

Glucose catabolism

The breakdown of glucose through pathways such as glycolysis to provide energy and metabolic intermediates

Glucose anabolism

The use of glucose or glucose derived intermediates to build and store molecules such as glycogen

Glycolysis location

The cytoplasm of the cell

Importance of glycolysis in red blood cells

Red blood cells lack mitochondria and depend on glycolysis for ATP production

Glycolysis and oxygen

Glycolysis does not directly require oxygen and can produce ATP under aerobic or anaerobic conditions

Overall glycolysis reaction

One glucose molecule is converted into two pyruvate molecules with a net production of two ATP and two NADH

Glycolysis phases

The preparatory phase consumes two ATP and the payoff phase produces four ATP and two NADH per glucose

Preparatory phase of glycolysis

The first five reactions that use two ATP to phosphorylate and split glucose derived intermediates into two three carbon molecules

Payoff phase of glycolysis

The final five reactions that produce four ATP two NADH and two pyruvate per glucose

Net ATP from glycolysis

Two ATP per glucose because four ATP are produced and two ATP are consumed

Gross ATP production in glycolysis

Four ATP are produced during the payoff phase for each glucose molecule

NADH production in glycolysis

Two NADH molecules are produced per glucose during oxidation of glyceraldehyde 3 phosphate

Pyruvate production in glycolysis

Two pyruvate molecules are produced from one glucose molecule

Step 1 of glycolysis

Glucose is phosphorylated to glucose 6 phosphate by hexokinase or glucokinase using ATP

Hexokinase

An enzyme found in most body tissues that phosphorylates glucose to glucose 6 phosphate

Glucokinase

An enzyme found mainly in liver cells and pancreatic beta cells that phosphorylates glucose to glucose 6 phosphate

Glucose 6 phosphate

The phosphorylated form of glucose produced during the first step of glycolysis that is retained inside the cell and can enter several metabolic pathways

Purpose of glucose phosphorylation

Adds a phosphate group that helps trap glucose inside the cell and prepares it for further metabolism

Hexokinase compared with glucokinase

Hexokinase is present in most tissues whereas glucokinase is concentrated in the liver and pancreatic beta cells

Step 2 of glycolysis

Glucose 6 phosphate is isomerized into fructose 6 phosphate

Isomerization

The rearrangement of atoms within a molecule to form an isomer without changing its molecular formula

Fructose 6 phosphate

A six carbon sugar phosphate formed from glucose 6 phosphate during glycolysis

Step 3 of glycolysis

Fructose 6 phosphate is phosphorylated by phosphofructokinase 1 to form fructose 1 6 bisphosphate using ATP

Phosphofructokinase 1 PFK 1

The major rate limiting regulatory enzyme of glycolysis that converts fructose 6 phosphate into fructose 1 6 bisphosphate

Rate limiting enzyme of glycolysis

PFK 1 which controls a major regulated step and strongly influences the rate of glycolysis

ATP regulation of PFK 1

High ATP inhibits PFK 1 and slows glycolysis because the cell has sufficient energy

AMP regulation of PFK 1

High AMP activates PFK 1 and stimulates glycolysis because the cell needs more energy

Fructose 1 6 bisphosphate

A six carbon phosphorylated sugar produced by PFK 1 that is split into two three carbon sugar phosphates

Step 4 of glycolysis

Fructose 1 6 bisphosphate is cleaved into glyceraldehyde 3 phosphate and dihydroxyacetone phosphate by aldolase

Aldolase

The glycolytic enzyme that splits fructose 1 6 bisphosphate into two three carbon sugar phosphates

Dihydroxyacetone phosphate

A three carbon sugar phosphate that can be converted into glyceraldehyde 3 phosphate during glycolysis

Step 5 of glycolysis

Dihydroxyacetone phosphate is converted into glyceraldehyde 3 phosphate by triose phosphate isomerase

Triose phosphate isomerase

The enzyme that interconverts dihydroxyacetone phosphate and glyceraldehyde 3 phosphate

Glyceraldehyde 3 phosphate

A three carbon sugar phosphate that enters the payoff phase of glycolysis and is oxidized to generate NADH

Step 6 of glycolysis

Glyceraldehyde 3 phosphate is oxidized and phosphorylated to form 1 3 bisphosphoglycerate while NADH is produced

First energy capturing reaction of glycolysis

Step 6 produces NADH through the oxidation of glyceraldehyde 3 phosphate

1 3 bisphosphoglycerate

A high energy intermediate formed from glyceraldehyde 3 phosphate that can donate a phosphate group to ADP to produce ATP

Step 7 of glycolysis

Phosphoglycerate kinase transfers a phosphate group from 1 3 bisphosphoglycerate to ADP to produce ATP and 3 phosphoglycerate

Phosphoglycerate kinase

The enzyme that catalyzes ATP production by transferring a phosphate from 1 3 bisphosphoglycerate to ADP

Substrate level phosphorylation

The direct formation of ATP or GTP by transferring a phosphate group from a high energy metabolic intermediate to ADP or GDP

First ATP producing step of glycolysis

Step 7 catalyzed by phosphoglycerate kinase

Step 8 of glycolysis

3 phosphoglycerate is rearranged into 2 phosphoglycerate by phosphoglycerate mutase

Phosphoglycerate mutase

The enzyme that moves the phosphate group from carbon 3 to carbon 2 of phosphoglycerate

Step 9 of glycolysis

2 phosphoglycerate loses water to form phosphoenolpyruvate

Enolase

The enzyme that catalyzes dehydration of 2 phosphoglycerate to produce phosphoenolpyruvate

Phosphoenolpyruvate PEP

A high energy three carbon intermediate that donates a phosphate group to ADP to generate ATP in the final step of glycolysis

Step 10 of glycolysis

Pyruvate kinase transfers a phosphate group from phosphoenolpyruvate to ADP producing ATP and pyruvate

Pyruvate kinase

The enzyme that catalyzes the final step of glycolysis by converting phosphoenolpyruvate into pyruvate while producing ATP

Final step of glycolysis

Conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase with ATP production

Net products of glycolysis

Two pyruvate two ATP net and two NADH per glucose with no carbon dioxide produced directly

Carbon dioxide production during glycolysis

Glycolysis does not directly release carbon dioxide because glucose is converted into two three carbon pyruvate molecules

Metabolic fate of pyruvate

Under aerobic conditions pyruvate is converted to acetyl CoA for oxidation while under anaerobic conditions it can be reduced to lactate to regenerate NAD plus

Aerobic conditions

Conditions in which oxygen is available to support mitochondrial respiration and oxidative metabolism

Anaerobic conditions

Conditions in which oxygen is unavailable or insufficient for the cell's metabolic needs

Pyruvate oxidation

The conversion of pyruvate into acetyl CoA with production of NADH and release of carbon dioxide

Acetyl CoA

A two carbon acetyl group carrier that enters the citric acid cycle by combining with oxaloacetate to form citrate

Lactate fermentation

The reduction of pyruvate to lactate by lactate dehydrogenase which regenerates NAD plus so glycolysis can continue without mitochondrial respiration

Lactate

A three carbon product formed from pyruvate during anaerobic glycolysis and capable of being transported to other tissues for metabolism

NAD plus regeneration

The restoration of oxidized NAD plus from NADH so glycolysis can continue producing ATP

Fermentation

A metabolic process that regenerates NAD plus by transferring electrons from NADH to an organic molecule such as pyruvate

Citric acid cycle

Also called the Krebs cycle or TCA cycle a mitochondrial pathway that oxidizes acetyl CoA derived acetyl groups to carbon dioxide while capturing energy in NADH FADH2 and GTP or ATP

Krebs cycle

Another name for the citric acid cycle

TCA cycle

Another name for the citric acid cycle referring to tricarboxylic acid intermediates

Citric acid cycle location

Mainly the mitochondrial matrix in eukaryotic cells

Citrate

The six carbon molecule formed in the first reaction of the citric acid cycle when acetyl CoA combines with oxaloacetate

Why the citric acid cycle is named after citrate

Citrate is the first major product formed when acetyl CoA enters the cycle

Acetyl CoA oxidation

The citric acid cycle oxidizes the two carbon acetyl group to carbon dioxide while capturing energy in reduced electron carriers

Number of reactions in the citric acid cycle

Eight enzyme catalyzed reactions complete one turn of the cycle

Products of one citric acid cycle turn

Two carbon dioxide three NADH one FADH2 and one GTP or ATP per acetyl CoA

Citric acid cycle carbon dioxide

Two carbon dioxide molecules are released per acetyl CoA oxidized in one turn of the cycle

Citric acid cycle NADH

Three NADH molecules are produced per turn of the cycle

Citric acid cycle FADH2

One FADH2 molecule is produced per turn of the cycle

Citric acid cycle GTP or ATP

One high energy nucleotide triphosphate is produced per turn of the cycle

Purpose of NADH and FADH2

Carry high energy electrons to the electron transport chain where their energy supports ATP production

Glucose to pyruvate

Glycolysis converts one six carbon glucose molecule into two three carbon pyruvate molecules in the cytoplasm

Pyruvate to acetyl CoA

Pyruvate oxidation converts pyruvate into acetyl CoA before the acetyl group enters the citric acid cycle

Glucose and citric acid cycle relationship

Each glucose yields two pyruvate and therefore two acetyl CoA which can complete two turns of the citric acid cycle

Cellular ATP yield from glucose

Complete aerobic oxidation of glucose typically produces about 30 to 32 ATP in eukaryotic cells depending on the shuttle systems and cellular conditions

Gluconeogenesis

The synthesis of glucose from simpler noncarbohydrate precursors such as lactate pyruvate glycerol and glucogenic amino acids

Main site of gluconeogenesis in mammals

The liver is the main site with the kidneys also contributing especially during prolonged fasting

Distribution of gluconeogenesis

Gluconeogenesis occurs in animals plants fungi and microorganisms although the tissues and regulation vary among organisms

Importance of gluconeogenesis

Maintains blood glucose when dietary glucose is unavailable or glycogen stores become insufficient

Gluconeogenesis precursors

Lactate pyruvate glycerol and glucogenic amino acids that can be converted into glucose through metabolic intermediates

Glucogenic amino acids

Amino acids whose carbon skeletons can undergo net conversion into glucose through pyruvate or citric acid cycle intermediates

Gluconeogenesis and glycolysis relationship

The pathways share several reversible reactions but differ at three major irreversible glycolytic steps that must be bypassed during glucose synthesis

Why gluconeogenesis is not the exact reverse of glycolysis

Three glycolytic reactions are strongly exergonic and effectively irreversible in cells so gluconeogenesis uses different bypass reactions