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Clinical Biochemistry
journal homepage: www.elsevier.com/locate/clinbiochem
Review
a r t i c l e
i n f o
Article history:
Received 17 October 2012
Received in revised form 18 April 2013
Accepted 20 April 2013
Available online 14 May 2013
Keywords:
Carbohydrate
Glycolysis
Pyruvate decarboxylation
Oxidative pathway
Pentose phosphate pathway
Glycogenesis
Glycogenolysis
Gluconeogenesis
a b s t r a c t
In mammals, there are different metabolic pathways in cells that break down fuel molecules to transfer their
energy into high energy compounds such as adenosine-5-triphosphate (ATP), guanosine-5-triphosphate
(GTP), reduced nicotinamide adenine dinucleotide (NADH2), reduced avin adenine dinucleotide (FADH2)
and reduced nicotinamide adenine dinucleotide phosphate (NADPH2). This process is called cellular respiration. In carbohydrate metabolism, the breakdown starts from digestion of food in the gastrointestinal tract
and is followed by absorption of carbohydrate components by the enterocytes in the form of monosaccharides. Monosaccharides are transferred to cells for aerobic and anaerobic respiration via glycolysis, citric
acid cycle and pentose phosphate pathway to be used in the starvation state. In the normal state, the skeletal
muscle and liver cells store monosaccharides in the form of glycogen. In the obesity state, the extra glucose is
converted to triglycerides via lipogenesis and is stored in the lipid droplets of adipocytes. In the lipotoxicity
state, the lipid droplets of other tissues such as the liver, skeletal muscle and pancreatic beta cells also
accumulate triacylglycerol. This event is the axis of the pathogenesis of metabolic dysregulation in insulin
resistance, metabolic syndrome and type 2 diabetes. In this paper a summary of the metabolism of carbohydrates is presented in a way that researchers can follow the biochemical processes easily.
2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Descriptions of gures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Carbohydrate digestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fructose metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Galactose metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Glucose oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Non-oxidative pathway (glycolysis) . . . . . . . . . . . . . . . . . . . . . . . .
Pyruvate decarboxylation (oxidative decarboxylation reaction) . . . . . . . . . . .
Oxidative pathway (Krebs cycle and OXPHOS reaction (electron transport chain)) . . .
Glycolysis (EmbdenMeyerhofParnas pathway) . . . . . . . . . . . . . . . . . . . .
Pyruvate dehydrogenase (PDH) or oxidative decarboxylation reaction . . . . . . . . . .
Regulation of PDH complex . . . . . . . . . . . . . . . . . . . . . . . . . . .
Krebs cycle (citric acid or tricarboxylic acid (TCA) cycle) . . . . . . . . . . . . . . . .
Malate-aspartate shuttle . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Energy balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TCA regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Glycogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Glycogenolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phosphorylase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pentose phosphate pathway (PPP), phosphogluconate pathway or hexose monophosphate
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Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. Fax: + 31 50
3632522.
E-mail address: M.Dashti.Rahmatabadi@med.umcg.nl.
0009-9120/$ see front matter 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clinbiochem.2013.04.027
Gluconeogenesis . . . . . . . . .
Cori cycle . . . . . . . . . .
Glucose-alanine cycle . . . .
Amino acids . . . . . . . . .
Glycerol . . . . . . . . . . .
Role of renal gluconeogenesis .
Regulation of gluconeogenesis
Conclusion . . . . . . . . . . . .
Acknowledgment . . . . . . . . .
References . . . . . . . . . . . .
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Introduction
The study of biochemistry is always one of the most complicated
topics among medical and biology students in spite of being one of the
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Graphic abstract gure. Presentation of the association between 6 biochemical pathways. The biochemical reactions happen in the cytoplasm or mitochondria;
therefore, a close interaction between these two parts always exists. These interactions are mostly, regulated by transporters that are in the mitochondrial membrane
(red ovals). The energetic pathways in the cell metabolize energetic molecules such as glucose and lipids. These pathways are glycolysis, gluconeogenesis, lipolysis,
lipogenesis and the electron transport chain. Pyruvate (product of glycolysis) can be used in amino acid reactions as well. The energetic products of the oxidative reaction of glucose in the mitochondria (NADH2 and FADH2) are delivered to the inner mitochondrial intermembrane (IMM) for complete conversion of their potential
energy to chemical energy in the form of ATP. ATP is the energetic parcel in cells that is used in different biochemical reactions. In this gure, the main energetic biochemical reactions and their association to each other are illustrated. These reactions are 1. Glycerol phosphate shuttle, 2. NADH2 shuttle into IMM, 3. Transhydrogenase
cycle (blue), 4. Citrate/malate cycle (pink), 5. Krebs cycle (red) and 6. Malate-aspartate shuttle (green). The correlative function of the lipid and carbohydrate biochemical
pathways together with the electron transport chain of the mitochondria for maintenance of glucose is also shown. Abbreviations are explained in gure 2.
1341
a way to facilitate the study of this topic and its link to other pathways.
The subjects that are investigated here are listed below:
1. Carbohydrate digestion (in the intestine)
2. Fructose metabolism (in the liver)
Fig. 2. Abbreviations.
5.
6.
7.
8.
(in the mitochondria) and the electron transport chain (ETC) (in
the inner mitochondrial membrane (IMM))
Glycogenesis (in the liver and skeletal muscle)
Glycogenolysis (in the liver, skeletal muscle and kidney)
Pentose phosphate pathway (in the liver, adipose tissue, adrenal cortex, testis, milk glands, phagocyte cells and red blood cells (RBCs))
Gluconeogenesis (in the liver, kidney, brain, testes and erythrocytes) [1].
Descriptions of gures
In this paper, the biochemical gures are shown in a new style in
order to facilitate the study and follow up of the pathways. Substrates
and products are presented in brown, enzymes in blue, number of carbons in each molecule in red, utilized materials at the left side and
yielded materials at the right side. S is the stimulators of the enzymes
and I is the inhibitors of the enzymes. Red arrows represent the inhibitory effects of agents. For interpretation of the references to color in the
gure legends, the reader is referred to the web version of this article.
Graphic abstract gure presents the association between pathways.
The general information of the pathways including formulas, abbreviations and a summary of the biochemical reactions in carbohydrate
metabolism are shown in gures 1, 2, 3 and table 1.
Carbohydrate digestion
Fructose metabolism
Dietary carbohydrates of greatest importance are composed of
hexoses such as sucrose (saccharose or table sugar), lactose (milk
sugar), galactose (derived from fermented products) and maltose
(derived from hydrolysis of starch) and also pentoses such as xylose
and arabinose (from fruits) [2]. Food digestion starts in the mouth
through secretion of salivary alpha-amylase (or ptyalin) that hydrolyses alpha-1,4 (-1,4) linkage of starch (or amylum) and converts it
to maltose. The next enzyme is pancreatic-amylase (or amylopsin) in
the small intestine that digests 60% of starches. Intestinal epithelial
cell enzymes degrade 6-carbon (6C-) carbohydrates [35]. These enzymes are lactase for degradation of lactose to glucose and galactose,
1343
Table 1
A summary of carbohydrate biochemical pathways. Numbering in glycolysis, PDH reaction and the Krebs cycle is based on breakdown of one glucose molecule. VR: Vital reaction,
C: Catabolic or exergonic reaction, A: Anabolic or endergonic reaction, Cyt: Cytoplasm, Mit: Mitochondria, 4C-P: Phosphorylated form of 4C-carbohydrate (erythrose-4P), 5C-P: Phosphorylated form of 5C-carbohydrate (xylulose-5P, riboluse-5P and ribose-5P), 7C-P: Phosphorylated form of 7C-carbohydrate (sedoheptulose-7P).
Pathway
Glycolysis (aerobic)
Glycolysis (anaerobic)
PDH reaction (aerobic)
Krebs cycle (aerobic)
Electron transport chain
Glycogenesis
Glycogenolysis
Gluconeogenesis
Fructose metabolism
Galactose metabolism
Pentose phosphate
VR
C
C
C
C
C
A
C
A
A
A
A
Place
Cyt
Cyt
Mit
Mit
Mit
Cyt
Cyt
Both
Cyt
Cyt
Cyt
Substrate
1 Glucose
1 Glucose
2 Pyruvate
2 Acetyl-CoA, 2 OAA
1 NADH2 & 1 FADH2
Glucose
Glycogen
2 Pyruvate (or 2 lactate)
Fructose
Galactose
G6P
Product
Utilized
2 Pyruvate
2 Lactic acid
2 Acetyl-CoA
2 Citrate
3 ATP & 2 ATP
Glycogen
G6P, glucose, F6P
G6P, glucose, F6P
G6P, glycogen
G6P, lactose
F6P, GA3P, 4C-P, 5C-P, 7C-P
Galactose metabolism
Galactose enters the body following consumption of milk. Milk
sugar or lactose is composed of galactose and glucose. Lactose is
converted to its constituents with lactase activity in the brush border
of the small intestine. Galactose enters the blood stream following absorption by enterocytes and enters the liver through the portal vein to
be metabolized and converted to glucose for consumption as energy.
Glucose and galactose are the sugars whose active forms are transferred
by the uridine diphosphate (UDP) coenzymes in the form of uridine
diphosphate-glucose (UDPG) and UDP-galactose (UDPGal). Galactose
metabolism starts from phosphorylation and conversion of galactose
to galactose-1-phosphate (Gal1P). Thereafter, galactose-1-phosphate
uridylyltransferase (GALT) and its UDPG coenzyme, exchange the
galactose of Gal1P with glucose to form G1P and as a result UDPGal is
2+
Yielded
Mg
Mg2+
Lipoic acid, 2 CoA
4 H2O, Fe2+, Mg2+, Mn2+, Fe/S
Oxygen
2 ATP, Mg2+
2 ATP, 2 NADH2
2 ATP
2 NADH2
6 NADH2, 4 CO2, 2 GTP, 2 FADH2, 2 CoA
H2O
2 NADPH2, 2 CO2, 6 Pi
Pi
2 NADPH2, 1 CO2, 1 H+
released. UDPGal can be converted to UDPG with UDP-galactose-4epimerase activity (Figs. 4 and 5).
Glucose oxidation
There are two non-oxidative and oxidative pathways that oxidize
glucose to prepare the energy source of cells. Oxidative decarboxylation
reaction is the linker reaction between these two pathways.
Non-oxidative pathway (glycolysis)
This is an anaerobic respiration or pyruvic acid (pyruvate) fermentation that happens in the cytoplasm in the absence of oxygen.
In glycolysis, partial oxidation of glucose produces pyruvic acid
(Fig. 6). In anaerobic states (heavy exercise or cells without
mitochondria), pyruvate is converted to lactate through a bilateral
reaction catalyzed by lactate dehydrogenase (LDH) and consumption of one molecule NADH2 (Fig. 3/12). Lactate is transferred to
the liver for gluconeogenesis and glucose production to be used
again in the glycolysis pathway (Cori cycle) (Fig. 7).
Pyruvate decarboxylation (oxidative decarboxylation reaction)
This reaction is the linker between glycolysis and the Krebs cycle
and is catalyzed by pyruvate dehydrogenase complex (PDC) (Fig. 8).
In this process, two pyruvic acids of the glycolysis pathway are consumed to produce two molecules of acetyl coenzyme A (acetyl-CoA)
Fig. 4. Presentation of the association between carbohydrate metabolisms. Galactose, fructose, mannose and glucose monosaccharides have a close association with each other and also
with the polysaccharide pathways including glycogenesis and glycogenolysis. In this gure, the roles of the main metabolic hormones on these pathways are also shown.
Abbreviations are explained in gure 2.
1345
Fig. 7. Cori cycle and glucose-alanine cycle. These are the cycles that link glucose production in the liver to energy production in other tissues. In the Cori cycle, bilateral association
between glycolysis in the skeletal muscle cells with gluconeogenesis in the hepatocytes is shown. Waste product of the skeletal muscles (lactate) is used in the hepatocytes to produce glucose for consumption as energy in the skeletal muscle. In the glucose-alanine cycle, the nitrogen product of non-hepatic tissues, produced from transamination reaction and
amino acid production, is transferred to the hepatocytes to be used for either gluconeogenesis and glucose production or excretion as urea. Abbreviations are explained in gure 2.
HK as well as GK (the specic kinase for glucose substrate) exist. Therefore, in high concentration of glucose (>100 mg/100 ml) GK is also active.
These enzymes are stimulated by insulin, adenosine monophosphate
(AMP) and adenosine diphosphate (ADP) and inhibited by long chain
fatty acids (LCFAs) and their own products, G6P and ATP. G6P is converted
to one 6C-F1,6BP molecule. Aldolase divides F1,6BP to two 3C-molecules,
namely DHAP or glyceraldehyde 3 phosphate (GA3P). These two molecules can be converted to each other using triosephosphate isomerase
(TPI). The high energy products of glycolysis pathway are ATP,
1,3-di(or bis)phosphoglyceric acid (1,3D(B)PGA) and phosphoenolpyruvate (PEP) that produce 8 kcal, 10 kcal and 14 kcal energy respectively. The nal product of the glycolysis pathway is two pyruvate molecules
that are used in the PDH reaction (Fig. 3/2). The allosteric enzymes of
glycolysis are phosphofructokinase (PFK), pyruvate kinase (PK) and
either GK or HK depending on the tissue.
One glucose produces 8 ATP during glycolysis. Glycolysis happens in two phases: preparatory and pay-off phases. In the preparatory phase, HK and PFK consume 2 ATP molecules. In the pay-off
phase glyceraldehyde-3-phosphate dehydrogenase (GA3PDH),
phosphoglycerate kinase (PGK) and PK produce 10 ATP via production of 2 NADH2 (equal to 6 ATP) and 4 ATP (Fig. 6).
In anaerobic states, each pyruvate produces lactate and 2 ATP by
utilizing one NADH2. Therefore, it produces 6 ATP less than the aerobic
state. Pyruvic acid is used in each of the following pathways and its nal
fate is regulated by acetyl-CoA (Fig. 10).
1.
2.
3.
4.
PDC loses its phosphate using PDH phosphatase and becomes active.
Insulin stimulates this reaction and consequently the Krebs cycle.
Mg 2 + and Ca 2 + are the stimulators of PDH phosphatase (Fig. 8).
The level of acetyl-CoA (product of PDH reaction) is the regulator
of PDK as well as PC (enzyme of gluconeogenesis) and the PDH itself
(enzyme of PDH reaction). Acetyl-CoA is also the substrate of FA synthesis and the Krebs cycle. Therefore, in the high level of acetyl-CoA
(or in excess of intracellular energy), gluconeogenesis (through OAA
production) and FA synthesis pathways are activated.
Translocation of the acetyl-CoA from the mitochondria to the cytoplasm happens via conversion to citrate. First, acetyl-CoA is converted
to citrate using citrate synthesis, and then citrate translocates to the cytoplasm and is degraded back to acetyl-CoA using citrate lyase. In the cytoplasm, acetyl-CoA carboxylase (ACC) converts acetyl-CoA to malonylCoA and proceeds toward the FA synthesis (Graphic abstract gure).
Malonyl-CoA is the inhibitor of carnitine palmitoyltransferase I (CPT-I)
and consequently FAO. This is the way that increased rate of glucose oxidation results in inhibition of FAO. The reason for high regulation of the
PDC is that there is no pathway in the body to convert acetyl-CoA to glucose. Adenosine monophosphate-activated protein kinase (AMPK) that
is the energy sensor of cells has the opposite effect on the function of
ACC. Low energy in cells stimulates both glucose degradation and the
function of AMPK. AMPK consequently inhibits ACC and decreases the
concentration of malonyl-CoA. As a result, FAO and production of
acetyl-CoA is increased.
Carbohydrates, lipids and amino acids are the substrates which
produce acetyl-CoA. Acetyl-CoA is used in different biochemical
pathways including (i) the Krebs cycle to produce H2O, CO2 and energy,
(ii) biosynthesis of cholesterol, squalene, bile acids, vitamin D3 and
steroidal hormones such as estrogen, progesterone, testosterone and
adrenal hormones, (iii) synthesis of FAs, (iv) synthesis of ketone bodies
such as acetone, beta-hydroxybutyric acid (BHB) and acetoacetic acid,
in the liver in starvation and the diabetic states and (v) synthesis of
acetylcholine that is the carrier of nerve impulses (Fig. 10).
Krebs cycle (citric acid or tricarboxylic acid (TCA) cycle)
Fig. 9. Tricarboxylic acid (TCA) cycle or Krebs cycle. The mitochondrial oxidative Krebs cycle is
a process, whereby the product of the PDH complex (acetyl-CoA) joins to OAA. In this process glucose is degraded to produce energetic molecules such as GTP, NADH2 and FADH2.
These reduced products release their energy in the IMM and via the OXPHOS reaction.
The gure and abbreviations are explained in the text and in gure 2.
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Fig. 10. Presentation of the linking role of pyruvate, G6P and acetyl-CoA in carbohydrate and lipid pathways. In this gure, the interrelation between glycogenesis, glycogenolysis, glycolysis, gluconeogenesis, the Krebs cycle, the urea cycle and hexose monophosphate (HMP) shunt (blue rectangle) is illustrated. In HMP shunt, G6P (product of glycogenolysis) is used in the pentose
phosphate pathway to produce Xu5P. Xu5P is also formed from F6P and GA3P by transketolase activity. Xu5P activates PP2A, which is the inducer of PFK2 and ChREBP. ChREBP is a lipogenic
transcription factor that which can induce triglyceride synthesis. Here also the linking role of pyruvate (product of glycolysis) and acetyl-CoA (product of PDH reaction) in carbohydrate and
lipid pathways are highlighted. As is shown, acetyl-CoA regulates the fate of pyruvate, gluconeogenesis and lipogenesis and is the substrate for acetylcholine, ketone bodies, biliary acids,
cholesterol, steroids and triglyceride synthesis. PDC is the main regulatory enzyme of acetyl-CoA. This complex is regulated by the PDH phosphatase and PDK enzymes. Ca2+ and Mg2+
are the activators of PDH phosphatase and the inhibitors of PDK. ATP, NADH2 and acetyl-CoA are the stimulators of PDK. The gure and abbreviations are explained in the text and gure 2.
Energy balance
Theoretically, 38 ATP molecules are made from one molecule of
glucose during cellular respiration. 8 ATP are directly formed from the
anaerobic glycolysis via degradation of one glucose molecule to two
pyruvate molecules. In the pyruvate decarboxylation reaction, each
3C-pyruvate produces one NADH2 (equal to 3 ATP). Therefore, each
6C-glucose in this reaction produces 6 ATP. In the Krebs cycle, the
total amount of energy that is made from each 3C-pyruvate is 12 ATP.
This amount is produced at the level of isocitrate dehydrogenase
(NADH2 = 3 ATP), -ketoglutarate dehydrogenase (NADH2 = 3
ATP), malate dehydrogenase (MDH) (NADH2 = 3 ATP), succinate dehydrogenase (FADH2 = 2 ATP) and succinate thiokinase (GTP). Since
each 6C-glucose molecule produces two 3C-pyruvate molecules, the
total amount of energy, which is made from one glucose is 24 ATP.
The 8 ATP of glycolysis, 6 ATP of the PDH complex and 24 ATP of the
Krebs cycle together produce 38 ATP.
Since the energy of each ATP is equal to 8 kcal, therefore the total
amount of the released energy is 304 kcal. This amount of obtained
energy in the chemical form is equal to 44% of the total amount of
energy which is measured by a calorimeter. Therefore, 56% of the
energy of glucose is released as heat to stabilize the body temperature. This wasting energy is through proton loss via the leaky mitochondrial membranes that ow back the protons from the IMS to the
matrix. Moreover, moving pyruvate and ADP into the mitochondrial
matrix requires energy. Therefore, in reality each glucose molecule
Fig. 11. Glycogenesis and glycogenolysis. Regulation of blood glucose is in close association with the biochemical regulation of glycogen pathways. G6P and F6P (products of glycolysis) are the
linkers of glycolysis and glycogen pathways. The gure and abbreviations are explained in the text and in gure 2.
[14]. Consequently, one group of pyrophosphate is made. Active glucose joins to the core of glycogen via -1/4 linkage using glycogen
synthase to elongate the glycogen molecule. By this way, C1 of
Fig. 12. Inuence of glucagon on carbohydrate pathways. In the fasted state, glucagon stimulates both liver glycogenolysis via activation of glycogen phosphorylase and gluconeogenesis via
stimulation of FBPase2 in order to elevate the blood sugar. Glucagon also inhibits glycogenesis via phosphorylation of glycogen synthase. Glucagon inuences beta receptors and uses
adenylate cyclase to stimulate conversion of ATP to cAMP. PKA is a protein kinase, which is cAMP-dependent and is activated through this receptor-mediated mechanism. The cAMP/
PKA complex phosphorylates (and activates) phosphorylase kinase (a form), which phosphorylates (and activates) phosphorylase (a form). Both phosphoprotein kinase and phosphorylase are dephosphorylated (and inhibited-b form) by phosphoprotein phosphatase. The inhibitor of phosphoprotein phosphatase is PPI1. PPI1 dephosphorylates (and inhibits) phosphorylase kinase (b form), phosphorylase (b form) and itself (b form). Phosphorylase kinase, phosphorylase and PPI1 are all activated (a-form) via phosphorylation by using ATP. PPI1
is phosphorylated (and activated) by cAMP/PKA and dephosphorylated (and inhibited-b form) by phosphoprotein phosphatase. Phosphorylase kinase is also activated by calcium
even without phosphorylation. This allows acetylcholine to increase glycogenolysis via neuromuscular stimulation and without receptor stimulation. In the normal state and excess
glucose, glycogenesis is activated and glycogenolysis is inhibited to reserve the glucose in the body. The gure and abbreviations are explained in the text and in gure 2.
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Fig. 13. Pentose phosphate pathway (PPP). PPP is a cytoplasmic pathway and is composed of
two oxidative and non-oxidative (highlighted) stages. This glucose oxidation pathway consumes G6P as substrate to produce F6P, Xu5P and NADPH2. NADPH2 is used in the lipid biochemical pathways. The gure and abbreviations are explained in the text and in gure 2.
Fig. 15. Association between glycolysis, gluconeogenesis and pentose phosphate pathways and the role of Xu5P (product of PPP) in PP2A activation and FA synthesis. Xu5P-activated PP2A
by using ATP and H2O and following activation of phosphoprotein phosphatase and hydroxylation of the PFK2/FBPase2 complex phosphorylates F6P to form F2,6BP. F2,6BP activates PFK1 (regulatory enzyme of glycolysis) and inhibits FBPase1 (regulatory enzyme of gluconeogenesis). These effects lead to increase in the level of F1,6 BP and glycolysis.
Xu5P-activated PP2A also activates ChREBP and gene expression of lipogenic enzymes, including ACL, ACC, and FAS. F1,6BP, PFK1 and FBPase1 are regulated by F2,6BP and the ratio of
ATP/ADP. In high level of F2,6BP and low level of this ratio, glycolysis will proceed maximally. The gure and abbreviations are explained in the text and gure 2.
Gluconeogenesis
Cori cycle
Glucose-alanine cycle
Alanine is another source of gluconeogenesis in the liver. Alanine
is produced from the transamination process in non-hepatic tissues.
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Regulation of gluconeogenesis
Fig. 16. Presentation of gluconeogenesis transcription factors. PGC1 is the key regulator of
gluconeogenesis. Glucagon/PKA phosphorylates CREB transcription factor and recruits
CBP coactivator to induce PGC1 coactivator. PGC1 coactivates and forms complexes
with other gluconeogenesis transcription factors including FOXO1, GR, HNF4 (as well
as PPAR) to induce the gluconeogenesis promoters. PEPCK and G6Pase are the gluconeogenesis genes (the same name of the related enzyme). AF2 is the PEPCK promoter and IRU
is the G6Pase promoter. Post-translational modication of PGC1 by reversible acetylation
and phosphorylation of PGC1 regulates the function of PGC1. Insulin/Akt inhibits
PGC1 via induction of PGC1 phosphorylation and degradation of the hepatic PGC1.
SIRT1 induces PGC1 activity via deacetylation of PGC1. SIRT1 stimulates gluconeogenesis through coactivation of FOXO1 and HNF4. GCN5 acetylates and inhibits PGC1 and
gluconeogenic activity. GCN5 is a member of the N-acetyltransferase superfamily. This gure
is mainly the idea of Sugden et al. The gure and abbreviations are explained in the text
and gure 2.
Conclusion
Energy homeostasis is one of the main tasks of the body. Regulation
and retour of energetic molecules like glucose and FAs is a complex process in the body in which all cells are involved. Adipose tissue, skeletal
muscle and liver are the main metabolic organs in the body. The normal
function of these metabolic organs is represented as normoglycemic
and normolipidemic states in the circulation. Understanding the
biochemistry of carbohydrates and lipids is one of the main steps towards comprehending the pathophysiology of metabolic diseases like
metabolic syndrome, diabetes and dyslipidemia. This review summarizes and illustrates a general view on the biochemistry of carbohydrates. The goal of this attempt is to facilitate the understanding of
complex biochemical pathways for researchers.
Acknowledgment
I would like to extend my appreciation to Dr Nessa Dashty
Rahmatabady for her useful comments in this paper.
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