Chapter 4 Carbohydrate Metabolism

Chapter 4 Carbohydrate Metabolism Weihong Hou

Deer derive energy from carbohydrate (cellulose) in the plants it consumes.

The functions of carbohydrate 1. The major function of carbohydrate is as a fuel to be oxidized and provide energy for other metabolic processes. Carbohydrate is the “staple food” for most organisms. Sugar and starch represent the major part of total caloric intake for humans. Glucose, the hydrolyzed product of starch mainly, is an important and common fuel. In mammals, glucose is the only fuel that the brain uses under non-starvation conditions and the only fuel that red blood cells can use at all. When 1 gram of carbohydrate is oxidized completely to CO2 and H2O, 4 kilocalories (66.8 kilo joule, kJ) of energy can be released.

The superstock

Overview of carbohydrate metabolism GLYCOGEN

Glycogenesis The storage of glucose in the form of glycogen for later use.

UDPG

Glycogenolysis The release of glucose from its storage form for use by cells

Pi

G-1-P G-6-P

GLUCOSE

6-phosphogluconate

Pentose phosphate pathway

Pi

Fructose 6-p

Anaerobic degradation (glycolysis)

non-carbohydrates trioses phosphate

energy

Glycolytic pathway

pyruvate

lactate

Formation of acetyl CoA Aerobic oxidation

end

acetyl CoA

Tricarboxylic acid cycle CO2 + H2O + energy

Oxidative phosphorylation

Gluconeogenesis

The formation of glucose from non-carbohydrates

Section I Glycolysis (Anaerobic Degradation) This pathway is universal pathway, an ancient pathway, may occur in all human cells. The complete glycolytic pathway was elucidated by 1940, largely through the pioneering contributions of Gustav Embden, Otto Meyerhof, Carl Neuberg, Jacob Parnas, Otto Warburg, Gerty Cori, and Carl Cori. Glycolysis is also known as the Embden-Meyerhof pathway. “Glycolysis” is derived from Greek words glycos (sugar, sweet) and lysis (dissolution)

The bivalve mytilus These mussels, inhabitants of the intertidal zone, display habitat-dependent anaerobiosis.

2. Another function of carbohydrate is as the structural elements in cell coat or connective tissues. 1).Glycoconjugates including glycoprotein, proteoglycan, and glycolipid have special functions, such as Protection (blood coagulation factors, immunoglobulin, glycosaminoglycan [as lubricant to lubricate skeletal joints]); Regulation (some hormones, some enzymes); Transportation (lipoprotein, transferrin); Receptors (some glycosyl chains of glycoconjugate extend on the surface of plasma membrane as antennae to form so called glycocalyx, to have the function of recognition, adhesion, and signal transduction). 2). Component of nucleic acids 3). Conversion to lipids and non-essential amino acids

1. Basic process of glycolysis 1-1 The degradation of glucose to triose phosphate 1-2 Conversion of triose phosphate to pyruvate 1-3 Conversion of pyruvate to lactate Triose phosphate Dihydroxyacetone phosphate glucose

Fructose 1,6-bisphosphate Glyceraldehyde 3-phosphate

phosphorylation

ATP production Pyruvate

Lactate reduction

GLYCOLYSIS

O ATP

CH2OH O

pyruvate c=o

CH2O

P OO-

2+

Mg

CH2O P

CH2OH

O

O

Hexokinase(HK) glucokinase(GK)

glucose COOH

AD P

isomerase G-6-P

fructose 6-phosphate

COOH lactate dehydrogenase

+

NADH+H

phosphofructokinase PFK

Mg2+

CHOH

CH3

ATP

ADP

CH2O

CH3

NAD lactate +

P O

CH2O

P

COOH

fructose 1,6-bisphosphate

Pyruvate (enol) COH

aldolase

CH2

Substrate level phosphorylation

ATP

CO¡« CH2

P

isomeraseCH2O P CHOH dihyroxy CH2O P acetone phosphate glyceraldehyde

Energy redistribution within molecules

3-phosphate NAD+

phosphoenol pyruvate enolase

NADH+H+

COOH

H2O

CHO P CH2OH

end

glycerate 2-phosphate

C O

CHO

pyruvate kinase ADP COOH

CH2OH

COOH

mutase

CHOH

ATP

ADP

COO¡«

CHOH

P

Phosphoglycerate CH2O P CH2O P kinase glycerate glycerate 1,3-bisphosphate 3-phosphate

Substrate level phosphorylation

H3PO4

glyderaldehyde 3-phosphate dehydrogenase

Energy redistribution within molecules

CH2OH O

glucose

ATP

2+

ADP

Mg hexokinase(HK) glucokinase(GK,liver)

CH2O P O

glucose 6-phosphate

4 points for this reaction:

1. Glucose as the form of glucose 6-phosphate is captured within cells,the phosphate ester can not penetrate the membrane. 2. The investor of this reaction is ATP, which as a phosphate donor provides energy to the reaction. Energy-consuming reaction and irreversible reaction. 3. HK is a key enzyme,can be inhibited by its product G-6-P, and has a high affinity (Km= 0.1mmol/L) for its substrate. 4. Glucokinase (GK) is the isoenzyme IV, present in liver. This enzyme has a higher Km (∼ 10mmol/L) for its substrate.

Vm

Hexokinase Concentration of blood sugar fluctuates at 3∼ 9 mmol/L which does not affect the velocity of the enzymatic reaction. Km=0.1mmol/L 0

0.1

Blood sugar 2 3 4 5

V

Glucokinase Concentration of blood sugar fluctuates at 3∼ 9 mmol/L which actually affects the velocity of the enzymatic reaction.

Blood sugar 0

2 4 6 8 10 12 14 16 18

Km=about 10mmol/L

Turn back

A summary a. b. c. d.

Location: cytosol Original material: glucose End product:lactate Key enzymes: Hexokinase (HK) Phosphofructokinase 1 (PFK-1) Pyruvate kinase (PK) a. Twice energy redistributions within molecule. Twice substrate level phosphorylations, net amounts of ATP produced are 2. a. Once dehydrogenation: oxidation Once hydrogenation: reduction

2. The regulation of glycolysis Glucagon ⊕

Glucose

ATP

ATP Adenylate cyclase cAMP

⊕

AMP

Citrate

Hormone regulation Covalent regulation Allosteric regulation

⊕

ADP

PFK-2 FBP-2 active inactive

Glucose 6-phosphate ATP

F-6-P ADP

glycolysis

Lactate

F-2,6-BP

PKA Phosphoprotein Phosphatase

ATP

PFK-1 ⊕ ADP ⊕ ⊕ F-1,6-BP

P

P

Pi

PFK-2 FBP-2 inactive active

⊕

Pi

end AMP

Citrate

Next

3. The significance of glycolysis • Glycolysis is the emergency energy-yielding pathway, such as run 100-meters dash, climb a mountain, standing high jump. •. Glycolysis is the main way to produce ATP in some tissues, even though the oxygen supply is sufficient, such as red blood cells, retina, testis, skin, medulla of kidney. • In clinical practice, such as heart failure, circulation failure, respiration failure, excessive loss of blood. Liu Xiang, a Chinese young sportsman, was the first oriental who won the golden medal in the 110meter hurdles at the Olympic Games

Section II Aerobic oxidation of glucose The process of oxidation completely from glucose to CO2 and H2O is named aerobic oxidation. This process is the major process to provide energy for most tissues. 1. The basic process of aerobic oxidation of glucose Glucose oxidation can be divided into 3 phases: a. Oxidation from glucose to pyruvate in cytosol b. Oxidation from pyruvate to acetyl CoA in mitochondria c. Tricarboxylic acid cycle and oxidative phosphorylation O2

O2 Glucose

G-6-P

Pyruvate

cytosol

Acetyl CoA Pyruvate

O2

H 2O H+ +e CO2

Tricarboxylic acid cycle

mitochondria

1-1 The oxidation of glucose to pyruvate 1-2 Pyruvate oxidative carboxylation

Mg2+

Pyruvate dehydrogenase complex of mammals including pyruvate dehydrogenase (20 or 30 chains) dihydrolipoyl transacetylase (60 chains) dihydrolipoyl dehydrogenase (6 chains) TPP, NAD+, FAD, CoA, Lipoic acid,

(a)

(b)

(c)

(a) Electron micrograph of the pyruvate dehydrogenase complex isolated from E.coli, showing its subunit structure. (b) In terpretive model of the enzyme from E. coli. Transacetylase (24 peptides) forms the cube-like core of the complex, pyruvate dehydrogenase (12 dimers) is distributed on the 12 edges of the cube, dihydrolipoyl dehydrogenase (6 dimers) on the six faces of the cube. (c) Interpretive model of the organization of the mammalian pyruvate dehydrogenase complex.

H3C

O

O

C

C

pyruvate

Pyruvate dehydrogenase complex

OH

S

OH S

oxidized lipoamide

S

(E1)

TPP

E2

E1

CH3 C

1

FAD

TPP

CO2

E2 E3

E1

FAD E3

S

H

hydroxyethyl TPP

2

(E2)

NADH+H+

5 (E3) oxidized lipoamide

NAD+

H3C

S

TPP

S

TPP

acetyl lipoamide FAD

E2 E3

E1

FADH2 E1

E 2 E3

dihydrolipoamide

E1:pyruvate dehydrogenase

E2:dihydrolipoamide transacetylase

E3:dihydrolipoamide dehydrogenase

3

TPP

FAD E1

CoASH (E2)

HS HS

4 (E3)

end

O HS C S

E2 E3

Pyruvate+NAD++HSCoA

H3C

O C¡« SCoA

acetyl CoA Acetyl CoA+NADH+H++CO2

1-3 Tricarboxylic acid cycle

Roundabouts,or traffic circles, function as hubs to facilitate traffic flow. The tricarboxylic acid cycle is the biochemical hub of the cell, oxidizing carbon fuels, usually in the form of acetyl CoA, interconversion of carbohydrates, lipids, and some amino acids, as well as serving as a source of precursors for biosynthesis.

O C

O

~

CH2 COOH

SCoACoASH COOH acetyl CoA CH3 C

CH2 COOH

oxaloacetate

NADH+H+

NAD

HO CH

COOH

CH2 COOH

malate H2O

H2O

citrate synthase

citrate

aconitase

fumarase

fumarate

succinyl CoA syntetase

CH2 COOH

succinate

COOH

cis-aconitate

CoASH GDP+Pi GTP

ADP

ATP

HO CH

COOH

isocitrate

+

NAD

isocitrate dehydrogenase

succinate dehydrogenase

CH2 COOH

CH

H2O

Tricarboxylic Acid Cycle

HOOC CH

FAD

C COOH

The first reaction in TCAC is the aconitase condensation of acetyl-CoA and oxaloacetate to form citrate. The CH2 COOH TCAC is also named citrate cycle. HC COOH

HC COOH

end

CH2 COOH

CH2 COOH

malate dehydrogenase

+

FADH2

H2O

HO C COOH

NADH+H+

+

NAD

NADH+H+

CO2

CH2 COOH

CH2 COOH

CH2

CH2

O C

~ SCoA

succinyl

CO2 O C COOH CoASH CoA α -ketoglutarate alpha-ketoglutarate dehydrogenase complex

Tricarboxylic acid cycle is also named Krebs cycle for the memory of the discover Hans Krebs. Hans Krebs was one of the great pioneers of modern biochemistry. He was born in Germany and received his medical education there. In 1932, when he was an assistant in medicine, he worked out the urea cycle with Kurt Henseleit, a medical student. In 1937, he discovered "tricarboxylic acid cycle" in England by himself. From 1954 on he was the head of the Department of Biochemistry at Oxford. He was retired from that position in 1967. He was still working actively until his death in 1981. The "tricarboxylic acid cycle" has been regarded as the most important single discovery in the history of metabolic biochemistry.

Table III-1 generation of ATP in aerobic oxidation of glucose pathway

Glycolytic pathway

Reactions Catalyzed by Glyceraldehyde 3-phosphate dehydrogenase

Phosphoglycerate kinase Pyruvate kinase

Methods of ATP production

Moles of ATP formed per mol of glucose

5 or 3

Respiratory chain Oxidation of 2 NADH

Phosphorylation at substrate level Phosphorylation at substrate level

Allow for consumption of ATP by reactions catalyzed by hexokinase and phosphofructokinase

2 2 -2

Production of Pyruvate dehydrogenase acetyl CoA complex

Respiratory chain Oxidation of 2 NADH

5

Tricarboxylic Isocitrate dehydrogenase acid cycle Alpha-ketoglutarate Dehydrogenase complex

Respiratory chain Oxidation of 2 NADH

5

Respiratory chain Oxidation of 2 NADH

5

Succinyl CoA synthetase

Phosphorylation at substrate level

Succinate dehydrogenase

Respiratory chain Oxidation of 2 FADH2

Malate dehydrogenase

Respiratory chain Oxidation of 2 NADH

2 3 5

Total per mole of glucose under aerobic conditions: 32 or 30 ATPs

2.The regulation of aerobic oxidation 1.1 Regulation of pyruvate dehydrogenase complex

pyruvate

acetyl CoA NAD+,CoA

acetyl CoA,NADH ATP,FA

Pyruvate dehydrogenase (active form)

AMP,CoA NAD+, Ca2+

Pi

ATP pyruvate dehydrogenase kinase ADP ADP,NAD+

NADH+H+, CO2

pyruvate dehydrogenase phosphatase H2O

Pyruvate dehydrogenase (inactive form)

insulin,Ca2+

Allosteric regulation and covalent modification

2.2 Regulation of tricarboxylic acid cycle

[NADH]/[NAD+] [ATP]/[ADP]

The activity of tricarboxylic acid cycle is inhibited

Section I I I The Pentose Phosphate Pathway (PPP) 1. The basic process: Oxidative phase (formation of pentose phosphate) Non-oxidative phase (group transferring) CH2O P O

G-6-P

NADP+

NADPH+H +

H2O CH2O P O

CH2O P OH

O

G-6-P dehydrogenase

COOH

lactonase

6-P-gluconate

6-P-gluconolactone

NADP+

CO2 CH2OH

glycolysis

transketolase transaldolase

6-P-gluconate dehydrogenase

C=O CHOH CHOH CH2O P

ribulose 5-phosphate

Location: cytosol Original material: glucose 6-phosphate End product: the intermediate products of glycolysis The coenzyme of dehydrogenation: NADP+

NADPH+H+

CH2OH C=O

4

CHOH

C=O

CHOH

HO CH

CH2OPO32-

CH2OPO32-

3

NADP+

O3-POCH2

xylulose 5-phosphate

COOH

6-phosphogluconate

2

CH2OPO3

O

6-phosphogluconolactone

ribose 5-phosphate

HO CH CH2OPO3

O

end

G-6-P

Pentose Phosphate Pathway

fructose 6-phosphate

CHOH

xylulose 5-phosphate 7 CHO

O3-POCH2

CH2OPO32-

CHOH 2-

1 2-

CHOH

CHO

NADPH+H

NADP

CHOH

sedoheptulose 7-phosphate

CH2OH

CHOH CH2OP32-

CHOH

2-

+

+

6

CHOH

CHOH

O

HO CH

HO CH

C=O H2O

C=O

C=O

CHOH CHOH

4

glyceraldehyde 3-phosphate CH2OH CH2OH

CHO CHOH

OH

O3-POCH2

4'

CO2

CH2OPO32-

5

CHOH

NADPH+H+

2-

CHOH

CHOH

ribulose 5-phosphate

2-

CH2OH

CHOH

CH2OPO32-

erythrose 4-phosphate CH2OH

glycolysis

C=O HO CH

CH2OPO32-

CHOH

glyceraldehyde 3-phosphate

CHOH CH2OP32-

fructose 6-phosphate

1. G-6-P dehydrogenase, 2. gluconolactone hydrolase, 3. 6-phosphogluconate dehydrogenase, 4. epimerase, 4'.isomerase, 5. 7. transketolase, 6. transaldolase

2. The significance of PPP 2-1 Ribose 5-phosphate 2-2 NADPH 1) Reducing power for biosynthesis of fatty acids, cholesterol, and so on. 2) Coenzyme of glutathione reductase to keep the normal level of reduced glutathione. NADPH+H+

NADP+ Glutathione reductase

G-S-S-G

2 GSH

2 H2O

H2O2

MHb

end

Hb

3) NADPH serves as the coenzyme of mixed function oxidases (monooxygenases). Biotransformation.

Deficiencies of certain enzymes of the PPP are major causes of hemolysis of red blood cells, resulting in one type of hemolytic anemia. There are 100 million people in the world suffering the deficiency of glucose 6phosphate dehydrogenase. When the susceptible people take some medicine such as antimalarial primaquine, aspirin, or sulfonamide, or eat broad bean (fava bean), hemolysis can be manifested. People may suffer from jaundice Vicia faba. The Mediterranean plant Vicia faba is a source of fava beans that contain the purine glycoside vicine.

Section IV glycogen Formation and Degradation

Glycogen granules

hepatocyte

α 1→4 glucosidic bond

High solubility and more reactive points for synthesis and degradation

2Pi

1. GLYCOGENESIS ATP

glucose

phospho glucomutase

ADP

Mg2+

GK(liver),HK

UTP (uridine triphosphate)

G-6-P

PPi

H2O

glycogen primer

UDP

branching enzyme

UDPG glycogen glycogen (uridine GLYCOGEN ¦Á-1,4-glycosidic ¦Á-1,4,¦Á-1,6diphosphate SYNTHASE glycosidic bond bond glucose) Pi debranching enzyme

G-1-P

glucose 6-phosphatase (liver)

PHOSPHORYLASE

2. GLYCOGENOLYSIS

O O

NH CH2OH O

O O

G-1-P

P

O O-

O-

O

N

O

+ -O P O P O P O CH2 O O-

O-

OH

UTP

H

H

OH

OH

O

PPi

NH CH2OH O

UDPG pyrophosphorylase

O O

P

N

O O

O-

P

O

O-

UDPG CH2OH

CH2OH

O

O-UDP UDPG

end

+

UDP

CH2OH

O

O

O

glycogen primer (n)

CH2OH

CH2OH

O

O

GLYCOGEN SYNTHASE

CH2OH

O

O

CH2 O H H H OH OH

O

O

glycogen (n+1)

O

O

Glycogenesis glycogen synthase

©–©–©–©–©–©–©–©–©–©–©– oligo¦Á-1,4

©–©–©–©–©–©–©–

¦Á-1,6-glucantransferase

(Branching enzyme)

©–©–©–©–

glycogen synthase

©–©–©–©–©–©–©–©–©–©–©–©– ©–©–©–©–©–©–©–©–©–©–©– ©–©–©–©–©–©–©–©–

oligo¦Á-1,4

¦Á-1,6-glucantransferase

©–©–©–©–©–©–©–©–©–©–©–©– end ©–©–©–©–©–©–©–©–©–©–©–©–

phosphorylase a

Glycogenolysis

phosphorylase a

14 glucose 1-phosphate

glucan transferase

glucosidase Debranching has two enzyme activities in one peptide: oligo α -1,4 α 1,4-glucantransferase andα 1,6-glucosidase

phosphorylase a

end

1 glucose

12 glucose 1-phosphate

3. Regulation of Glycogenesis and Glycogenolysis

hormons:glucagon, epinephrine

inactive adenylate cyclase

active adenylate cyclase ATP

cAMP

inactive protein kinase A

ATP

active protein kinase A

P phosphorylase b kinase

ADP

ATP

ATP

ADP

H2O

ADP

P P

glycogen synthase (active)

Pi

phosphorylase b kinase

phosphorylase b

glycogen synthase (inactive)

phosphorylase a

Pi

H2O

glycogenolysis

Pi

protein phosphatase-1

H2O

glycogenesis

end

inhibitor-1 (inactive)

ATP

inhibitor-1 (active)

P

4. The significance of glycogenesis and glycogenolysis

Liver glycogen (as much as 10% of liver wet weight) functions as a glucose reserve for maintaining blood glucose concentration. Muscle glycogen (total 400 gram) serves as a fuel reserve for synthesis of ATP within that tissue.

Section V Gluconeogenesis The process of transformation of non-carbohydrates to glucose or glycogen is termed as gluconeogenesis. 1. The basic process of gluconeogenesis Essentially a reversal of glycolysis with three barriers circumvented by four additional enzymes: Glc

G-6-P

F-6-P

F-1,6BP

GAP

DHAP

1,3-BPG

3-PG

2PG

PEP

Oxaloacetate Lactate

1) from pyruvate to phosphoenolpyruvate: pyruvate carboxylase phosphoenol pyruvate carboxykinase 2) from fructose 1,6-phosphate to fructose 6-phosphate fructose 1,6-bisphosphatase 3) from glucose 6-phosphate to glucose glucose 6-phosphatase

Pyruvate

1-1 The conversion of pyruvate to phosphoenol pyruvate glycolysis ATP

ATP CO2

PK

ADP

CH3

CH3

C O pyruvate COOH

C O¡« P CH2

pyruvate carboxylase (in Mt)

biotin

ADP + Pi

COOH CH2 C O COOH

phosphoenol pyruvate GDP

CO2

phosphoenol pyruvate carboxykinase (1/3 in Mt, 2/3 in Cytosol) GTP O

gluconeogenesis

biotin

C

oxaloacetate HN

NH

HC HC H2C

HC S

(CH2)4 COOH

1-2 The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate glycolysis ADP

ATP Mg2+

phosphofructokinase 1 fructose 1,6-bisphosphate

fructose6-phosphate fructose 1,6bisphosphatase

H2O

Pi

gluconeogenesis

1-3 The conversion of glucose 6-phosphate to glucose glycolysis ATP

ADP Mg2+

glucokinase glucose 6-phosphate

glucose glucose 6phosphatase liver Pi

H2O

gluconeogenesis

Substrate cycle is a pair of opposed irreversible reactions. Substrate cycle or futile cycle: nothing is accomplished but the waste of ATP. In substrate cycle, ATP is formed in one direction and then is hydrolyzed in the opposite direction. Substrate cycle produces net hydrolysis of ATP. We must remember that the direction of the substrate cycle is strictly controlled by allosteric effectors to meet the needs of the body for energy. Bumblebee must maintain a thoracic temperature of about 30°C to fly. A bumblebee is able to maintain this high thoracic temperature and forage for food even when the ambient temperature is only 10 °C because phosphofructokinase and fructose 1,6bisphosphatase in its flight muscle are simultaneously highly active; the continuous hydrolysis of ATP generates heat. In contrast, the honeybee has almost no fructose 1,6-bisphosphatase in its flight muscle and consequently cannot fly when the ambient temperature is low.

glucose glycogen

GLUCONEOGENESIS

UDPG G-6-P G-1-P

F-6-P

CYTOSOL

F-1,6BP

dihydroxyacetone phosphate

glyceraldehyde 3phosphate

MITOCHONDRIA

malic acid

malic acid

Glutamate a-ketoglutarate

1.3-diphosphoglycerol glycerate oxaloacetate

aspartate

Glutamate a-ketoglutarate

aspartate

NAD+ NADH+H+

oxaloacetate

GTP

glycerate 3-P glycerate 2-P

end

lactate

ADP + Pi

2/3 CO2 GDP

phosphoenol pyruvate

pyruvate

biotin CO2 ATP

pyruvate

2. The significance of gluconeogenesis 2-1 To keep blood sugar level stable Gluconeogenesis meets the demands of the body for glucose when carbohydrate is not available in sufficient amount from the diet. For a person each day brain spent 125g of glucose renal medulla erythrocytes 50g retina skeletal muscle 50g The liver is only able to deposit about 100-150g of glucose as the form of glycogen. More than 25% of glucose is supplied by gluconeogenesis.

2-2 To replenish liver glycogen 2-3 To regulate acid-base balance phosphoenolpyruvate carboxykinase induces biosynthesis

gluconeogenesis alpha-ketoglutarate NH3

glucose H+ NH4+

glutamic acid NH3

glutamine

H+

NH4+excreted in urine and pH raised in blood

Na+ absorbed

urine

2-4 To clear the products of other tissues ’ metabolites from the blood. 2-5 To convert glucogenic amino acids to glucose. 3. Cori cycle glucose

glucose

glycolytic pathway

gluconeogenesis

pyruvate

pyruvate

NADH+H+

+

NAD

+

NADH+H

lactate

liver

glucose

NAD+

lactate

lactate

BLOOD

muscle

4.Regulation of gluconeogenesis and glycolysis F-6-P ATP citrate ADP AMP F-2,6-BP F-1,6-BP

F-1,6-biphosphatase

phosphofructokinase-1

F-1,6-BP insulin

glycolysis

gluconeogenesis

glucokinase

pyruvate carboxylase

phosphofructokinase-1

phosphoenolpyruvate carboxykinase

pyruvate kinase

fructose 1,6-biphosphatase glucose 6-phosphatase

end glucagon

Glucocorticoids epinephrine

Section VI Blood Sugar and Its Regulation origin (income)

fate (outcome) aerobic oxidation

dietary supply liver glycogen non-carbohydrate (gluconeogenesis)

Blood sugar 3.89~6.11mmol/L

glycogenesis PPP etc

other saccharides

glycogen other saccharides

non-carbohydrates (lipids and some amino acids)

>8.89¡« 10.00mmol/L (threshold of kidney)

urine glucose

end

CO2 + H2O + energy

The Metabolic Changes on High Blood Sugar Level High blood sugar level (hyperglycemia) insulin released insulin receptor active transport in muscle and adipose tissue cells (not in liver and brain)

cAMP 1 3

5

5 2

lipogenesis

glycogenesis

gluconeogenesis

2

6

glycolysis and aerobic oxidation

end

4

modulating system

glycogenolysis

lipolysis

protein synthesis

Metabolic Changes on Low Blood Sugar Level Low blood sugar level (hypoglycemia) glucagon

cAMP 1

hepatic glycogenolysis

Modulating system 3

gluconeogenesis

end

4

3

1 2

lipolysis transport of glucogenic amino acids

hepatic glycogenesis glycolysis

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