Cellular Biochemistry and metabolism 2 Lecturer of Biochemistry

Slides:



Advertisements
Similar presentations
Biochemistry Lecture 11.
Advertisements

Gluconeogenesis and PPP C483 Spring An intermediate found in gluconeogenesis and not glycolysis is A) 2-phosphoglycerate. B) oxaloacetate. C)
Lecture 12 Modified from internet resources, journals and boks
Gluconeogenesis Synthesis of "new glucose" from common metabolites
DR AMINA TARIQ BIOCHEMISTRY
Introduction of Glucose Metabolism
Biochemistry department
Regulation of Glycolysis & Gluconeogenesis
Regulation of Glycolysis & Gluconeogenesis Copyright © by Joyce J. Diwan. All rights reserved. Molecular Biochemistry I.
Glycolysis and Gluconeogenesis Alice Skoumalová.
Pathways for Pyruvate The pyruvate produced from glucose during glycolysis can be further metabolized in three possible ways For aerobic organisms, when.
Gluconeogenesis (formation of new sugar) 1. Why gluconeogenesis?
Gluconeogenesis.
Gluconeogenesis : An overview
Formation of glucose from noncarbohydrate sources
Overview of catabolic pathways
Glycogen Metabolism 23.8 Gluconeogenesis: Glucose Synthesis Chapter 23 Metabolic Pathways for Carbohydrates.
Gluconeogenesis.
Biochemistry 432/832 September 03 Chapter 23 G&G Gluconeogenesis Glycogen metabolism.
KULSOOMKULSOOM KULSOOMKULSOOM KULSOOMKULSOOM KULSOOMKULSOOM Gluconeogenesis Dr. Bibi Kulsoom.
CARBOHYDRATE METABOLISM. METABOLISM? WHY?  A 59-year-old man with a history of diabetes and alcohol abuse is brought to the emergency room in a semiconscious.
Professor of Biochemistry Gluconeogenesis
Metabolism of glycogen. Regulation of glycogen metabolism Regulating site for glycogen synthesis Glycogen synthase Regulating site for glycogen catabolism.
Additional Pathways in Carbohydrate Metabolism
BIOC DR. TISCHLER LECTURE 26 GLYCOLYSIS AND GLUCONEOGENESIS-2
Fig 10.5 Overview of catabolic pathways Prentice Hall c2002 Chapter 11.
Prentice Hall c2002Chapter 131 Chapter 13 Additional Pathways in Carbohydrate Metabolism Insulin, a 51 amino acid polypeptide that regulates carbohydrate.
UNIT II: Intermediary Metabolism
Gluconeogenesis Dr. Tarek A Salem.
CHO Metabolism. In mammals, some tissues depend almost completely on glucose for their metabolic energy The brain alone requires about 120 g of glucose.
Glycolysis and Gluconeogenesis
Biosynthesis of glucose – gluconeogenesis Carbohydrates provide a significant portion of human caloric intake.
Cellular Biochemistry and Metabolism (CLS 331) Dr. Samah Kotb Nasr Eldeen.
We eat, we digest, we absorb, then what? Three fates for nutrients 1)Most are used to supply energy for life 2)Some are used to synthesize structural or.
© 2012 Pearson Education, Inc. CHEMOTROPIC ENERGY:GLYCOLYSIS AND FERMENTATION Chapter 9.
Carbohydrate metabolism. CHO supply Diet Endogenous reserves –Liver –Muscle –Blood Limited Anaerobic glycolysis –Anaerobic Does not need oxygen Occurs.
1 Carbohydrate metabolism Intermediary Metabolism Elizabeth F. Neufeld Suggested reference: Champe, Harvey and Ferrier, Lippincott’s Illustrated Reviews.
Glycolysis and Gluconeogenesis Dr M. D. Lloyd 5W 2.13;
Regulation of Glycoysis. Pyruvate can go in three major directions after glycolysis Under aerobic conditions pyruvate is oxidized to Acetyl-CoA which.
Overview of Glucose Metabolism
CHAPTER 17 Gluconeogenesis.
Carbohydrate anabolism We have covered some aspects of carbohydrate catabolism: glycolysis, PPP, citric acid cycle, etc. and now we turn to carbohydrate.
Gluconeogenesis; Regulation of Glycolysis & Gluconeogenesis Copyright © by Joyce J. Diwan. All rights reserved. Molecular Biochemistry I.
After Digestion And Absorption
DENTAL BIOCHEMISTRY 2015 LECTURE 10 GLUCONEOGENESIS Michael Lea.
Gluconeogenesis.
Chapter 18 Storage Mechanisms and Control in Carbohydrate Metabolism Mary K. Campbell Shawn O. Farrell Paul.
Gluconeogenesis.
GLUCONEOGENESIS Summary of handout:
Glycolysis Regualtion
Hormonal regulation and pathologies of carbohydrate metabolism. Diabetes mellitus.
Gluconeogenesis. gluco neo genesis sugar (re)new make/ create glycolysis glucose pyruvate lactate gluconeogenesis.
Gluconeogenesis Anabolic pathway that makes glucose from pyruvate Net result = reverse of glycolysis Three topics: 1. Thermodynamics 2. Enzymes 3. Regulation.
Gluconeogenesis How to synthesize glucose from noncarbohydrate precursors? p.543.
1 GLUCONEOGENESIS Summary of handout: Comparison with glycolysis, unique and shared enzymes "Reversal" of pyruvate kinase. Participation of the mitochondria.
BIOC/DENT/PHCY 230 LECTURE 11. o glucose requirements:160g/day whole body (120g/day brain) o glucose reserves:190g glycogen 20g in body fluids o need.
Storage Mechanisms and Control in Carbohydrate Metabolism Apr. 7, 2016 CHEM 281.
GLYCOLYSIS Learning objectives: List the enzymes and intermediates involved in glycolysis List the irreversible and regulated steps of glycolysis Discuss.
MIA KUSMIATI Departemen BIOKIMIA FK UNISBA.  The stimulation of gluconeogenesis by high energy charge and high concentrations of citrate and acetyl-CoA.
Gluconeogenesis  is not a reversal of glycolysis  noncarbohydrate precursors of Glc, carbon skeleton  take place in liver, minor in kidney, brain, skeletal.
Glycolysis Alice Skoumalová. Glucose: the universal fuel for human cells Sources:  diet (the major sugar in our diet)  internal glycogen stores  blood.
Dr. Ng’weina Francis Magitta, MD, PhD University of Dar es Salaam 2015
Gluconeo- genesis Carbohydrates provide a significant portion of human caloric intake.
Gluconeogenesis.
Glycolysis and Gluconeogenesis
GLUCONEOGENESIS Synthesis of glucose from noncarbohydrate precursors
Gluconeogenesis.
22.7 Gluconeogenesis: Glucose Synthesis
Gluconeogenesis.
Biochemistry of Metabolism
Presentation transcript:

Cellular Biochemistry and metabolism 2 Lecturer of Biochemistry Gluconeogenesis Cellular Biochemistry and metabolism 2 CLS 333 Dr. Samah Kotb Lecturer of Biochemistry 2015

Chapter 3 Gluconeogenesis Dr.Samah Kotb

Gluconeogenesis Gluconeogenesis Is the formation of glucose from non-carbohydrate sources e.g lactic acid ,amino acids , glycerols and propionate. occurs mainly in liver . Gluconeogenesis occurs to a more limited extent in kidney & small intestine under some conditions.  Dr.Samah Kotb

Gluconeogenesis Synthesis of glucose from pyruvate utilizes many of the same enzymes as Glycolysis. Three Glycolysis reactions have such a large negative DG that they are essentially irreversible. Hexokinase (or Glucokinase). Phosphofructokinase. Pyruvate Kinase. These steps must be bypassed in Gluconeogenesis. Two of the bypass reactions involve simple hydrolysis reactions. Dr.Samah Kotb

Gluconeogenesis Liver and kidney contains all enzymes of gluconeogenesis. It does not occur in skeletal muscles due to deficiency of glucose-6-phosphatase. It does not occur in heart muscle, smooth muscles, and adipose tissues due to deficiency of fructose 1-6 diphosphatase. Dr.Samah Kotb

Importance of gluconeogenesis Glucose is the only source of energy: Nervous system Skeletal system Glucose is required : 1) Adipose tissues: as a source of glycerol. 2) Mammary gland: as a source of lactose.

gluco neo genesis sugar (re)new make/ create glucose glycolysis pyruvate lactate sugar (re)new make/ create

Gluconeogenesis Occurs in all animals, plants, fungi and microbes. Occurs largely in the liver; some in renal cortex. Of 10 enzymatic steps, 7 are reversals of glycolytic reactions.

Dr Samah Kotb

Hexokinase or Glucokinase (Glycolysis) catalyzes: glucose + ATP  glucose-6-phosphate + ADP Glucose-6-Phosphatase (Gluconeogenesis) catalyzes: glucose-6-phosphate + H2O  glucose + Pi Dr.Samah Kotb

The catalytic site is found to be exposed to the ER lumen. Glucose-6-phosphatase enzyme is embedded in the endoplasmic reticulum (ER) membrane in liver cells. The catalytic site is found to be exposed to the ER lumen. Dr.Samah Kotb

Phosphofructokinase (Glycolysis) catalyzes: fructose-6-P + ATP  fructose-1,6-bisP + ADP Fructose-1,6-bisphosphatase (Gluconeogenesis) catalyzes: fructose-1,6-bisP + H2O  fructose-6-P + Pi Dr.Samah Kotb

Bypass of Pyruvate Kinase: Pyruvate Kinase (last step of Glycolysis) catalyzes: phosphoenolpyruvate + ADP  pyruvate + ATP For bypass of the Pyruvate Kinase reaction, cleavage of 2 ~P bonds is required. DG for cleavage of one ~P bond of ATP is insufficient to drive synthesis of phosphoenolpyruvate (PEP). PEP has a higher negative DG of phosphate hydrolysis than ATP. Dr.Samah Kotb

Bypass of Pyruvate Kinase (2 enzymes): Pyruvate Carboxylase (Gluconeogenesis) catalyzes: pyruvate + HCO3- + ATP  oxaloacetate + ADP + Pi PEP Carboxykinase (Gluconeogenesis) catalyzes: oxaloacetate + GTP  PEP + GDP + CO2 Dr.Samah Kotb

Contributing to spontaneity of the 2-step process: Free energy of one ~P bond of ATP is conserved in the carboxylation reaction. Spontaneous decarboxylation contributes to spontaneity of the 2nd reaction. Cleavage of a second ~P bond of GTP also contributes to driving synthesis of PEP. Dr.Samah Kotb

Summary of Gluconeogenesis Pathway: Gluconeogenesis enzyme names in red. Glycolysis enzyme names in blue. Dr.Samah Kotb

Dr.Samah Kotb

Glycolysis & Gluconeogenesis are both spontaneous. If both pathways were simultaneously active in a cell, it would constitute a "futile cycle" that would waste energy. Glycolysis: glucose + 2 NAD+ + 2 ADP + 2 Pi  2 pyruvate + 2 NADH + 2 ATP Gluconeogenesis: 2 pyruvate + 2 NADH + 4 ATP + 2 GTP  glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi Dr.Samah Kotb

Regulation of Gluconeogenesis Dr.Samah Kotb

To prevent the waste of a futile cycle, Glycolysis & Gluconeogenesis are reciprocally regulated. Local Control includes reciprocal allosteric regulation by adenine nucleotides. Phosphofructokinase (Glycolysis) is inhibited by ATP and stimulated by AMP. Fructose-1,6-bisphosphatase (Gluconeogenesis) is inhibited by AMP. Dr.Samah Kotb

Regulation of Gluconeogenesis The opposite effects of adenine nucleotides on Phosphofructokinase (Glycolysis) Fructose-1,6-bisphosphatase (Gluconeogenesis) Insures that when cellular ATP is high (AMP would then below), glucose is not degraded to make ATP. When ATP is high it is more useful to the cell to store glucose as glycogen. When ATP is low (AMP would then be high), the cell does not expend energy in synthesizing glucose. Dr.Samah Kotb

Regulation of Gluconeogenesis Global Control in liver cells includes reciprocal effects of a cyclic AMP cascade, triggered by the hormone glucagon when blood glucose is low. Phosphorylation of enzymes & regulatory proteins in liver by Protein Kinase A (cAMP Dependent Protein Kinase) results in inhibition of glycolysis stimulation of gluconeogenesis, making glucose available for release to the blood. Dr.Samah Kotb

Summary of effects of glucagon-cAMP cascade in liver: Gluconeogenesis is stimulated. Glycolysis is inhibited. Glycogen breakdown is stimulated. Glycogen synthesis is inhibited. Free glucose is formed for release to the blood. Dr.Samah Kotb

Regulation of Gluconeogenesis Enzymes relevant to these pathways that are phosphorylated by Protein Kinase A include: Pyruvate Kinase, a glycolysis enzyme that is inhibited when phosphorylated. CREB (cAMP response element binding protein) which activates, through other factors, transcription of the gene for PEP Carboxykinase, leading to increased gluconeogenesis. A bi-functional enzyme that makes and degrades an allosteric regulator, fructose-2,6-bisphosphate. Dr.Samah Kotb

Reciprocal regulation by fructose-2,6- bisphosphate Fructose-2,6-bisphosphate stimulates Glycolysis. Fructose-2,6-bisphosphate allosterically activates the Glycolysis enzyme Phosphofructokinase. Fructose-2,6-bisphosphate also activates transcription of the gene for Glucokinase, the liver variant of Hexokinase that phosphorylates glucose to glucose-6-phosphate, the input to Glycolysis. Fructose-2,6-bisphosphate allosterically inhibits the gluconeogenesis enzyme Fructose-1,6-bisphosphatase. Dr.Samah Kotb

The Cori Cycle Dr.Samah Kotb

Cori Cycle The Cori Cycle operates during exercise. For a brief burst of ATP utilization, muscle cells utilize ~P stored as phosphocreatine. Once phosphocreatine is exhausted, ATP is provided mainly by Glycolysis, with the input coming from glycogen breakdown and from glucose uptake from the blood. (Aerobic fat metabolism , is more significant during a lengthy period of exertion such as a marathon run.) Dr.Samah Kotb

The glucose may travel back to the muscle to fuel Glycolysis. Lactate produced from pyruvate passes via the blood to the liver, where it may be converted to glucose. The glucose may travel back to the muscle to fuel Glycolysis. Dr.Samah Kotb

The Cori cycle costs 6 ~P in liver for every 2 ~P made available in muscle. The net cost is 4 ~P. Although costly in ~P bonds, the Cori Cycle allows the organism to accommodate to large fluctuations in energy needs of skeletal muscle between rest and exercise. Dr.Samah Kotb

Cori Cycle The equivalent of the Cori Cycle also operates during cancer. If blood vessel development does not keep pace with growth of a solid tumor, decreased O2 concentration within the tumor leads to activation of signal processes that result in a shift to anaerobic metabolism. Dr.Samah Kotb

Energy dissipation by the Cori Cycle, which expends 6 ~P in liver for every 2 ~P produced via Glycolysis for utilization within the tumor, is thought to contribute to the weight loss that typically occurs in late-stage cancer even when food intake remains normal. Dr.Samah Kotb