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GLUCOSE METABOLISM

Jose Gabriel Zabala Quintero Spanish

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GLUCOSE METABOLISM

GLUCONEOGENESIS
- Purpose
  - It is responsible for maintaining blood glucose levels during periods of fasting
    - Through the synthesis of new glucose
      - From
        Lactate
        Generated from anaerobic glycolysis
        By fabrics like
        Muscles
        Erythrocytes
        Destination place
        Liver
        Upon reaching the liver, it can be converted into glucose by gluconeogenesis
        Glucose will return to
        Muscles
        Erythrocytes
        Forming the Cori cycle
        Glycerol
        It comes from the breakdown of triglycerides
        Circulate freely in the bloodstream
        Destination place
        Liver
        Upon reaching the liver, it is phosphorylated by
        Glycerol kinase
        Producing Glycerol Phosphate
        Glycerol phosphate is oxidized by
        Glycerol phosphate dehydrogenase
        Producing dihydroxyacetone phosphate
        Dihydroxyacetone phosphate DHAP is a glycolytic intermediate
        Glycogenic amino acids
        Upon reaching the Krebs cycle, they are metabolized into
        Alpha-ketoglutarate
        Succinil CoA
        Fumarate
        Through PEP carboxykinase they become in
        Oxaloacetate
        Through PEP carboxykinase it is converted to
        Phosphoenolpyruvate (PEP), which is a glycolytic intermediate
- When does it start?
  - Starts when glycogen stores in the liver run out
    - After about a 24-hour fast
- Unique enzymes
  - Pyruvate Carboxylase
  - PEP carboxylase
  - Fructose 1,6-bisphosphatase
  - Glucose 6-phosphatase
- Occurs in specific tissues
  - Liver
    - The only tissues to have the enzymes necessary for gluconeogenesis
  - Kidney
- Who regulates it?
  - It is regulated by the levels of
    - Growth hormone
    - Catecholamines
    - Cortisol
      - Acts as a promoter of gluconeogenesis
        Increases the enzymes needed to convert amino acids into glucose
        In the liver
    - Insulin
      - Acts as an inhibitor of gluconeogenesis
      - Upon reaching the cell, it activates the AKT signaling pathway, which will cause
        The inhibition of FOXO, having as a consequence
        Decreased gluconeogenesis
      - Having a decrease in insulin
        FOXO is activated
        Generating increased gluconeogenesis
        Allows catabolism of
        Fats
        Protein
        Which will give us a greater availability of
        Gluconeogenic substrates
    - Glucagon
      - It is produced
        In
        Alpha cells of the pancreas
        By
        Decrease in blood glucose levels.
      - Action mechanisms
        Favors or promotes the catalytic activity of
        fructose 1,6-bisphosphatase
        Promotes gluconeogenesis
        Converts fructose-1,6-bisphosphate to fructose-6-phosphate
        Adenylate cyclase
        Increases cAMP concentrations intracellularly
        Causing the activation of the
        CAMP-dependent protein kinase, is inactive to
        Pyruvate kinase.
        It is responsible for converting PEP to pyruvate
        When it is inhibited, it generates an increase in PEP, generating a greater glycogenic substrate
        PEP-carboxykinase
        Increase PEP production
        Generating greater glucose production
        Suppress
        Phosphofructokinase-1
        It is the main regulatory enzyme of glycolysis
- Pathophysiology associated with a failure of glucose 6- phosphatase
  - Von Gierke disease
    - Condition in which the body cannot break down glycogen
      - glucose 6 phosphatase deficiency
    - Autosomal recessive inherited disease
  - Hyperkalemia
  - Hyperuricemia
    - It is characterized by an abnormal elevation of serum uric acid
  - Increased lactate levels
  - The reticular response
    - It occurs due to an increase in GNG in the liver
      - Causing
        Diabetes
        Obesity
KREBS CYCLE
- Action mechanisms
  - Through the following image you can observe the events that happen in the Krebs cycle, showing the changes that the sutrates undergo when entering it, we can also show the enzymes that act and the respective products
    - This is a closed circuit of eight main stages in which the last part of the pathway regenerates the molecule used in the first step (oxaloacetate)
  - Dehydrogenases
    - They allow the carbon atoms in each triose to convert to carbon dioxide
    - Are
      - Pyruvate dehydrogenase
      - Isocitrate dehydrogenase
      - Alpha ketoglutarate dehydrogenase
        They decarboxylate the different substrates of the Krebs cycle
        Generating CO2 production
  - As there are many reduced coenzymes, the Krebs cycle stops
    - Reduced coenzymes associated with the Krebs cycle
      - NADH
      - FADH2
- End products of the Krebs cycle
  - 2 molecules of CO2
  - Energy products
    - 3 molecules of NADH2
    - 3 molecules of NADH2
    - 1 molecule of ATP
      - Having a total of 12 ATP molecules
        As glucose breaks down into 2 pyruvates at the end of glycolysis, it will generate at the end of the Krebs Cycle a total of
        24 ATP molecules
- Vitamins necessary for the Krebs cycle
  - Vitamin B1 (Thiamine)
  - Vitamin B2 (Riboflavin)
  - Vitamin B3 (Niacin)
- Pathophysiology
  - Beriberi
    - Generated by Thiamine deficiency
    - High levels of Pyruvate in the blood
      - Which tells us that there are defects in pyruvate oxidation
  - Fumarase deficiency
    - It is an autosomal inheritance
    - Characterized by a deficiency of the enzyme hydratase fumarate
      - Indicated by an accumulation of fumaric acid in the urine.
  - Prostate cancer
    - It is caused by the deficiency of the enzyme aconitase
      - Results in citrate to isocitrate oxidation
    - It only occurs in the male gender, because women do not have a prostate
    - Symptoms
      - Problems urinating
      - Pain when ejaculating
      - Blood in urine or semen
      - Pain in the back side of the back
  - Mitochondrial encephalomyopathy
    - It occurs due to the deficiency of succinate dehydrogenase
    - Caused by gene mutation
    - Symptoms
      - Muscular weakness
      - Exercise intolerance
      - Hearing loss
      - Convulsions
      - Loss of balance
      - Progressive weakness
      - Heart failure
      - Learning deficit
- Purpose
  - Metabolic route by which we can metabolize the different remnants of the food that we previously digested in order to obtain energy
    - Of fundamental importance in all cells that use oxygen during the process of cellular respiration.
      - Occurs in the mitochondrial matrix
        It cannot happen in erythrocytes
GLYCOLYSIS
- Action mechanisms
  - Glucose travels through the bloodstream to enter cells
    - It will enter through insulin and the different types of receptors (GLUT) of each cell
      - Cellular glucose receptors (GLUT)
        GLUT3 (Not insulin dependent)
        Brain
        GLUT 2 (Not insulin dependent)
        Liver
        GLUT 1 (Not insulin dependent)
        Erythrocytes
        GLUT 1 (Insulin dependent)
        Muscle
        Tejido adiposoAdipose tissue
        Some heart cells
    - Glucose upon entering the cell is phosphorylated by
      - Hexokinase
        Producing glucose-6-phosphate
        Glucose-6-phosphate is isomerized by
        Phosphohexose isomerase
        Producing fructose-6-phosphate
        Fructose-6-phosphate is phosphorylated by
        Fosfofructoquinasa-1
        Producing fructose 1,6-bisphosphate
        Fructose 1,6-bisphosphate is catalyzed by
        Aldolasse
        Producing
        Dihydroxyacetone phosphate
        Triose phosphate isomerase allows these two compounds to be isomerized with each other
        Producing Glyceraldehyde-3-phosphate
        The same thing will happen to this compound as to the first Glyceraldehyde-3-phosphate compound that was generated previously
        Glyceraldehyde-3-phosphate
        Glyceraldehyde-3-phosphate is phosphorylated by
        Glyceraldehyde-3-phosphate dehydrogenase
        Producing 1,3-bisphosphoglycerate
        1,3-bisphosphoglycerate is catalyzed by
        Phosphoglycerate kinase
        Producing 3 - phosphoglycerate
        3-phosphoglycerate is isomerized by
        Phosphoglycerate mutase
        Producing 2-phosphoglycerate, which is hydrolyzed by
        Enolase
        Producing Phosphoenolpyruvate
        Phosphoenolpyruvate is dephosphorylated by
        Pyruvate kinase
        Producing
        Pyruvate, which enters the Krebs cycle as Acetyl-CoA
        Producing ATP at the same time from the phosphorylation of ADP
        H2O is also produced from H
        Producing ATP at the same time from the phosphorylation of ADP
        NADH2 is also produced from NAD
        Producing ADP at the same time from the use of ATP
        Uses Mg to trap ATP and phosphorylate glucose
      - Producing ADP at the same time from the use of ATP
- Types
  - Anaerobic glycolis
    - It is the process that occurs from the arrival of glucose to the cell, generating different transformations to glucose until reaching the point where glucose becomes pyruvate
    - It occurs only at the cytosolic level
    - From 1 glucose molecule, 4 ATP can be generated, for each triose 2 ATP are generated and in total we have 2 ATP consumed during its entire process. Therefore we have 4 ATP left at the end of glycolysis
  - Aerobic glycolysis
    - Aerobic glycolysis is the stage in which pyruvate enters the mitochondria and is decarboxylated, becoming Acetyl Co-a in order to enter the Krebs cycle.
    - Upon reaching oxidative phosphorylation, an average of 36 ATP is produced
    - It occurs only in the mitochondria
- Who regulates it?
  - It is regulated by the levels of
    - ADP
      - Having high levels of ADP promotes
        The transformation of fructose-6-phosphate to fructose 1,6-bisphosphate
    - ATP
      - Inhibits
        The transformation of fructose-6-phosphate to fructose 1,6-bisphosphate
        By increase in ATP concentration
        The transformation of phosphoenolpyruvate to pyruvate
      - Promueve
        Glycogenolysis
        By decrease in ATP concentration
    - Acetyl-CoA
      - Promotes lipogenesis
        Due to the decrease in the levels of Acetyl Co.A
      - Inhibits the passage of phosphoenolpyruvate to pyruvate
        By increasing the concentration of Acetyl Co-A
    - Citrate
      - Inhibits the phosphorylation of fructose 6 phosphate to fructose 1,6 bisphosphate
- Associated pathologies
  - Tarui disease
    - It is a metabolic disease due to a deficiency in the enzyme phosphofructokinase
      - Phosphofructokinase converts Fructose 6-phosphate to Fructose 1,6-bisphosphate
        It occurs in step 3 of glycolysis
    - It is a hereditary, autosomal recessive disease
    - It manifests itself in certain cells, such as erythrocytes and skeletal muscle, losing the ability to use glucose as a source of energy
    - It belongs to the group of glycogenosis
      - Diseases produced by storage or accumulation of glycogen
      - They are inherited disorders that affect the formation and use of glycogen
    - Symptoms
      - Exercise intolerance
      - Cramps
      - Myoglobinuria
        Expulsion of myoglobin through urine
- Purpose
  - First metabolic route to obtain energy from carbohydrates that we ingest every day
PENTOSA PHOSPHATE
- Purpose
  - Its purpose is the production of
    - NADPH2
      - From glucosea
      - It is involved in the synthesis of biomolecules
        Sterols
        Nucleic acids
        Nonessential amino acids
        Fatty acids
    - Ribose
      - Precursora de ácidos Nucleicos
        How
        DNA
        RNA
  - Maintain carbon homeostasis in the cell
- Branches after the first step of glycolysis
  - Taking Glucose 6 phosphate as the first substrate
- Associated pathologies
  - Chronic granulomatous disease
  - Neuromuscular diseases
  - Cancer.
  - Diabetes mellitus type 2
- Action mechanisms
  - It occurs through two phases
    - Phases
      - Oxidative
        Starts from the branching of the first step of glycolysis
        It takes Glucose 6 phosphate as the first substrate and catalyzes it by means of
        Glucose 6 phosphate dehydrogenase
        Producing 6-phosphogluconolactone
        6-phosphogluconolactone is hydrolyzed by
        6-phosphogluconolactonase
        Generating 6-phosphogluconate
        6-phosphogluconate is catalyzed by
        6-Phosphogluconate dehydrogenase
        Producing ribulose 5-phosphate
        Ribulose 5-phosphate is isomerized by
        Phosphopentose isomerase
        Producing ribose 5 phosphate
        Nucleic acid precursor
        At the same time produce
        CO2
        NADPH2 from NADP
        Producing at the same time H from H2O
        NADH2 is also produced from NADP
      - Non oxidative
        Occur in the cytosol
        Composed of a series of reversible transfer reactions of chemical groups
        Starts with ribulose 5 phosphate
        Catalyzed by
        Phosphopentose epimerase
        Producing
        Xylulose 5-phosphate
        Xylulose 5-phosphate
        The union of these two by means of a trancetolase will produce
        Fructose 6-phosphate
        Glyceraldehyde 3-phosphate
        Phosphopentose isomerase
        Producing ribose 5-phosphate
        The union of these two by means of a transketolase will produce
        Sedoheptulose 7-phosphate
        The union of these two by means of a transaldolase will produce
        Eritrosa 4-phosphate
        Fructose 6-phosphate
        These three final products will pass to the glycolytic pathway to serve as a substrate in obtaining energy or obtaining glycogen
        Glyceraldehyde 3 phosphate

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Description: Mind Map on GLUCOSE METABOLISM, created by Jose Gabriel Zabala Quintero on 27/09/2020.
Created by: Jose Gabriel Zabala Quintero
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