eMedicine Specialties > Neurology > Pediatric Neurology

Disorders of Carbohydrate Metabolism: Multimedia

Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Contributor Information and Disclosures

Updated: Apr 23, 2009

Multimedia

Ketone metabolism.
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Media file 1: Ketone metabolism.
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Ketone metabolism.

Ketone metabolism.

Krebs cycle.
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Media file 2: Krebs cycle.
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Krebs cycle.

Krebs cycle.

Metabolism of galactose. The galactose ring diffe...
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Media file 3: Metabolism of galactose. The galactose ring differs from glucose in that the hydroxyl group (OH) at carbon-3 is up and not down. To convert galactose to glucose, the ring is first bound to uridine diphosphate (UDP). In this form, the sugar moiety can be epimerized, putting the OH down and forming glucose. The UDP-glucose then is converted to glucose-1-phosphate, then to glucose-6-phosphate, and subsequently metabolized further.
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Metabolism of galactose. The galactose ring diffe...

Metabolism of galactose. The galactose ring differs from glucose in that the hydroxyl group (OH) at carbon-3 is up and not down. To convert galactose to glucose, the ring is first bound to uridine diphosphate (UDP). In this form, the sugar moiety can be epimerized, putting the OH down and forming glucose. The UDP-glucose then is converted to glucose-1-phosphate, then to glucose-6-phosphate, and subsequently metabolized further.

Structure of glycogen. The rings each indicate a ...
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Media file 4: Structure of glycogen. The rings each indicate a glucose moiety in glycogen. These are linked by an ether bond between carbon-1 of one moiety and carbon-4 of the next. In the hydrolysis of glycogen, glycogen phosphorylase (ie, phosphorylase) catalyses the hydrolysis of the glucose moiety from the nonreducing end of glycogen to glucose-1-phosphate and a glycogen chain 1 unit shorter in length than the original. Phosphoglucomutase converts the glucose-1-phosphate to glucose-6-phosphate. Glucose-1-phosphate can then be metabolized, eg, by glycolysis. The branches of glycogen comprise 1-6 ether links. These have to be broken by the glycogen debranching enzyme. In fact, the debranching enzyme has to act before phosphorylase can hydrolyze moieties within 5 units of a branch point. In defects of phosphorylase, glycogen cannot be broken down in the tissue lacking the enzyme; therefore, glycogen accumulates, eventually in very large amounts. In defects of the debrancher, the breakdown of glycogen stops when 5 glucose units still are present near the branch point in any direction. Short branches of glycogen accumulate.
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Structure of glycogen. The rings each indicate a ...

Structure of glycogen. The rings each indicate a glucose moiety in glycogen. These are linked by an ether bond between carbon-1 of one moiety and carbon-4 of the next. In the hydrolysis of glycogen, glycogen phosphorylase (ie, phosphorylase) catalyses the hydrolysis of the glucose moiety from the nonreducing end of glycogen to glucose-1-phosphate and a glycogen chain 1 unit shorter in length than the original. Phosphoglucomutase converts the glucose-1-phosphate to glucose-6-phosphate. Glucose-1-phosphate can then be metabolized, eg, by glycolysis. The branches of glycogen comprise 1-6 ether links. These have to be broken by the glycogen debranching enzyme. In fact, the debranching enzyme has to act before phosphorylase can hydrolyze moieties within 5 units of a branch point. In defects of phosphorylase, glycogen cannot be broken down in the tissue lacking the enzyme; therefore, glycogen accumulates, eventually in very large amounts. In defects of the debrancher, the breakdown of glycogen stops when 5 glucose units still are present near the branch point in any direction. Short branches of glycogen accumulate.

Glycolysis. The names of sugars are given with a ...
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Media file 5: Glycolysis. The names of sugars are given with a "-" to separate the phosphate moiety so as to emphasize the name of the sugar at each step. As the first step in glycolysis, glucose must enter the cell. Entry is highly dependent on insulin and the reactions at and adjacent to the cell membrane, which are induced by insulin. Next, glucose is given a phosphate handle, so the enzymes of glycolysis (and those of the pentose shunt, glycogen synthesis, further metabolic steps) can handle glucose. When glucose comes from glycogen, it is in the form of glucose-1-phosphate, which has to be converted to glucose-6-phosphate. The glucose moiety is isomerized to fructose, and a second phosphate handle is added to the 6-carbon chain. The chain is then split into two 3-carbon units, each with a phosphate handle.

Only one of the 2 forms of P-3-carbon can be metabolized further. The inert form, dihydroxyacetone phosphate, is converted into the active form via the enzyme triosephosphate isomerase. Two molecules of ATP are used up in giving the 6-carbon chain its 2 handles. Nicotine adenine diphosphate (NAD+) is reduced to NADH in the dehydrogenase reaction. In pure glycolysis, these are restored in the oxidative reactions that convert the triose phosphates to pyruvate and the reduction of pyruvate to lactic acid. At the same time, since 2 3-carbon moieties are oxidized for each single 6-carbon moiety that goes down the pathway, 2 extra ATPs are formed. Pure glycolysis thus can generate energy anaerobically. In aerobic metabolism, the bulk of the pyruvate is converted to acetyl coenzyme A rather than to lactate.
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Glycolysis. The names of sugars are given with a ...

Glycolysis. The names of sugars are given with a "-" to separate the phosphate moiety so as to emphasize the name of the sugar at each step. As the first step in glycolysis, glucose must enter the cell. Entry is highly dependent on insulin and the reactions at and adjacent to the cell membrane, which are induced by insulin. Next, glucose is given a phosphate handle, so the enzymes of glycolysis (and those of the pentose shunt, glycogen synthesis, further metabolic steps) can handle glucose. When glucose comes from glycogen, it is in the form of glucose-1-phosphate, which has to be converted to glucose-6-phosphate. The glucose moiety is isomerized to fructose, and a second phosphate handle is added to the 6-carbon chain. The chain is then split into two 3-carbon units, each with a phosphate handle.

Only one of the 2 forms of P-3-carbon can be metabolized further. The inert form, dihydroxyacetone phosphate, is converted into the active form via the enzyme triosephosphate isomerase. Two molecules of ATP are used up in giving the 6-carbon chain its 2 handles. Nicotine adenine diphosphate (NAD+) is reduced to NADH in the dehydrogenase reaction. In pure glycolysis, these are restored in the oxidative reactions that convert the triose phosphates to pyruvate and the reduction of pyruvate to lactic acid. At the same time, since 2 3-carbon moieties are oxidized for each single 6-carbon moiety that goes down the pathway, 2 extra ATPs are formed. Pure glycolysis thus can generate energy anaerobically. In aerobic metabolism, the bulk of the pyruvate is converted to acetyl coenzyme A rather than to lactate.

Scheme of the major reactions of the pyruvate deh...
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Media file 6: Scheme of the major reactions of the pyruvate dehydrogenase complex. Initial oxidative decarboxylation of pyruvate is shown as reaction (1), transfer of the 2-carbon moiety to the lipoyl side chain of lipoyl acetyltransferase (E2) as reaction (2), formation of acetyl coenzyme A as reaction (3), oxidation of the lipoyl moiety as reaction (4), and reduction of NAD as reaction (5). The regulatory enzymes acting on pyruvate decarboxylase (E1) are not shown.
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Scheme of the major reactions of the pyruvate deh...

Scheme of the major reactions of the pyruvate dehydrogenase complex. Initial oxidative decarboxylation of pyruvate is shown as reaction (1), transfer of the 2-carbon moiety to the lipoyl side chain of lipoyl acetyltransferase (E2) as reaction (2), formation of acetyl coenzyme A as reaction (3), oxidation of the lipoyl moiety as reaction (4), and reduction of NAD as reaction (5). The regulatory enzymes acting on pyruvate decarboxylase (E1) are not shown.

Major metabolic relations of pyruvate. Many of th...
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Media file 7: Major metabolic relations of pyruvate. Many of the reactions, such as those between glucose-6-phosphate and pyruvate, pyruvate and alanine, and pyruvate and lactate, are of course reversible. Abbreviations: LDH - lactic dehydrogenase; PDH - pyruvate dehydrogenase complex; p carboxylase - pyruvate carboxylase; TCA cycle - Krebs tricarboxylic acid cycle; KGDH-a-ketoglutarate dehydrogenase complex.
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Major metabolic relations of pyruvate. Many of th...

Major metabolic relations of pyruvate. Many of the reactions, such as those between glucose-6-phosphate and pyruvate, pyruvate and alanine, and pyruvate and lactate, are of course reversible. Abbreviations: LDH - lactic dehydrogenase; PDH - pyruvate dehydrogenase complex; p carboxylase - pyruvate carboxylase; TCA cycle - Krebs tricarboxylic acid cycle; KGDH-a-ketoglutarate dehydrogenase complex.

Fructose metabolism. In muscle and most tissue, t...
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Media file 8: Fructose metabolism. In muscle and most tissue, the same hexokinase that phosphorylates glucose to glucose-6-phosphate also phosphorylates fructose to fructose-6-phosphate. Fructose-6- phosphate then undergoes metabolism, down to pyruvate or up to glycogen, through the enzymes of glycolysis. In the liver, fructose is phosphorylated largely to the 1-phosphate form and converted to glyceraldehydes and dihydroxyacetone phosphate. Free glyceraldehydes can be phosphorylated by a specific kinase; this and dihydroxyacetone are metabolized further by the reactions of glycolysis.
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Fructose metabolism. In muscle and most tissue, t...

Fructose metabolism. In muscle and most tissue, the same hexokinase that phosphorylates glucose to glucose-6-phosphate also phosphorylates fructose to fructose-6-phosphate. Fructose-6- phosphate then undergoes metabolism, down to pyruvate or up to glycogen, through the enzymes of glycolysis. In the liver, fructose is phosphorylated largely to the 1-phosphate form and converted to glyceraldehydes and dihydroxyacetone phosphate. Free glyceraldehydes can be phosphorylated by a specific kinase; this and dihydroxyacetone are metabolized further by the reactions of glycolysis.

More on Disorders of Carbohydrate Metabolism

References
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Further Reading

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Keywords

acquired carbohydrate metabolism disorders, inborn errors of metabolism, inherited metabolism disorders, inherited disorders of carbohydrate metabolism, diabetic ketoacidosis, diabetes, hyperosmolar coma, hypoglycemia, episodic lactic acidosis in infancy, failure to thrive, hypotonia, mental retardation, storage disorders, polyneuropathy, peripheral nerve disease

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Contributor Information and Disclosures

Author

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart Association, American Stroke Association, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine
Disclosure: Abbott Labs  Honoraria Consulting; Teva Marion Honoraria Consulting; Boeringer-Ingelheim Honoraria Speaking and teaching

Medical Editor

Beth A Pletcher, MD, Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey
Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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