Metabolic Pathways: Glycolysis, Gluconeogenesis, and More PDF

**METABOLIC PATHWAYS** **-** a pathway where glucose is utilized to create energy (ATP) **DIFFERENT TYPES OF METABOLIC PATHWAYS** \* **GLYCOLYSIS**- "Embden-Meyerhof" Pathway -breakdown glucose to form pyruvate with the release of ATP molecules \* **GLUCOGENESIS**- Conversion of non-glucose hex...

**METABOLIC PATHWAYS** **-** a pathway where glucose is utilized to create energy (ATP) **DIFFERENT TYPES OF METABOLIC PATHWAYS** \* **GLYCOLYSIS**- "Embden-Meyerhof" Pathway -breakdown glucose to form pyruvate with the release of ATP molecules \* **GLUCOGENESIS**- Conversion of non-glucose hexoses: (Mannose, Fructose, Galactose) which are usually converted into glucose. \* **GLYCOGENESIS**- Synthesis of excess glucose. Can be stored into Glycogen. \* **GLYCOGENOLYSIS**- 1^st^ process of glycogenesis. Where breakdown of glycogen to glucose is done. \- will utilize ATP \- Regulated by Glucagon \* During the breakdown of all metabolic pathways of CHO, ATP is being utilized\* \* **PENTOSE PHOSPHATE PATHWAY***/ [hexose monophosphate shunt/ phosphogluconate oxidative pathway]*- Alternative pathway where glucose molecules are catabolized and form ATP molecules \* **KREB'S CYCLE**/ *[citric acid cycle/ tricarboxylic cycle]*- Main pathway that produces ATP. \- Final common pathway to produce ATP **[\*GLUCONEOGENESIS\*]** - Conversion of non-CHO sources like (proteins) Amino Acids, glycerol (lipids), and lactate to CHO substrates. \- These CHO substrates will now enter the Kreb's cycle for the production of ATP.\ - Involves **"[Transdeamination"- ]**Removal and transfer of amino groups.\ - (Matatanggalan si amino group and will be transferred sa ibang group) Ex: **INTERCONVERSION BETWEEN MONOSACCHARIDES IN THE LIVER**- process of **[glucogenesis]** (fructose, galactose, mannose) will turn into glucose and glucose will be broken down for preparation to form ATP. \* Most human tissues cannot utilize galactose and fructose (need to undergo glycogenesis). Galactose and Fructose Glucose Blood and Other cells \* **[Liver cells]** contain all appropriate enzymes needed to promote interconversions between the monosaccharides to produce glucose \*Both end products of galactose and fructose is the glucose-6-Phosphate that will be converted into glucose\* **FRUCTOSE METABOLISM** \- **[Liver, kidneys, intestine, and adipose tissue]** can utilize fructose as an energy source. \- FRUCTOKINASE- Phosphorylates fructose to fructose-1-P \- HEXOKINASE- Phosphorylates fructose to fructose-6-PO4\ - Has higher affinity for glucose compared to fructose \* The relative abundance of glucose in the liver competitively inhibits the phosphorylation of fructose because hexokinase picks "has a higher affinity" the conversion of glucose\* \+ ALDOLASE- Utilizes **fructose-1,6 diphosphate** (produce: [glyceraldehyde-3-P,] and *[dihydroxyacetone Phosphate]*) as substrate **CLINICAL SIGNIFICANCE OF FRUCTOSE IN THE BODY** **\* FRUCTOSURIA-** caused by Lack of fructokinase\ - inability of the body to absorb fructose.\ - Fructose is being excreted in the urine Symptoms: Benign and asymptomatic\ - Maybe misinterpreted as glucosuria (positive reducing sugar test) because of it\ being positive in the urine "false positive for glucose" \* **FRUCTOSE INTOLERANCE-** caused by lack of Aldolase- which cleaves fructose into triose sugars (fructose-1-P, 1,6 Diphosphate, fructose-6-P, 2-Glucose-6-P)\ - Body is also not able to absorb fructose.\ - Fructose-1-PO4 inhibits glycogenolysis and gluconeogenesis. Since there is lack\ of aldolase, until fructose-1-PO4 and mamemetabolize ng body.\ - Prolonged intake of fructose by infants: **[vomiting, poor feeding, jaundice and\ ] [hepatic failure, death]** [Symptoms]: Hypoglycemia and vomiting following sucrose (since sucrose is hydrolyzed\ into fructose and glucose, and our body cannot absorb and use fructose, fructose will\ then be excreted in the urine, causing hypoglycemia and vomiting). [Medication]: There is no medication but patient can remain symptom free as long as they\ don't intake sucrose or anything that will produce fructose. DIET. **GALACTOSE METABOLISM** \- Galactose is obtained from milk sugar\ - most important organs that can metabolize galactose are liver, and RBC  \- **GALACTOSEMIA-** has a defect in 2 enzymes either: Galactose-1-PO4 Uridyl Transferase or Galactokinase. Galactose-1-P will be trapped in our liver cells and RBCs and galactose will not be metabolized which will lead to **HEMATOMEGALY (**Enlargement of liver**) impairing it and mental retardation.** **GALACTITOL-** alcohol that is produced when galactose is not metabolized.\ - can cause cataracts due to deposition in the eye lens **[TREATMENT FOR GALACTOSEMIA]**: Eliminate Milk products so lactose will not be converted into galactose and wont be metabolized by the body. **[\*GLYCOGENESIS\*]**- Liver, muscle cells: main storage of glucose (ALL cells of the body are capable of storing atleast some glycogen.) -maintains blood sugar Normal tissues: store 300-320 grams/day\ **Exceed of excess glycogen becomes fat (no storage limit)** 2 FORMS OF GLYCOGEN STORAGE: 1. FREE GLYCOGEN- can readily be released (LIVER) 2. FIXED GLYCOGEN- one that can be released slowly (MUSCLE) HOW DOES GLYCOGENOLYSIS WORK During hepatic metabolism of Glycogen it's going to produce glucose but metabolism in the muscle will only produce glucose-6- phosphate **- IN hypoglycemia-** before phosphorylation happens it should be activated in the presence of enzyme **phosphorylase** which will initiate phosphorylation ad glycogenolysis **GLUCAGON & EPINEPHRINE**- hormones responsible for **initiation of phosphorylase**. During phosphorylation, phosphorylase will attack the glycogen bonds (a-1,4 bonds) molecule of the glucose residues until the branch points are reached, then dextrins will be produced.\ **LIVER GLYCOGENOLYSIS** can initiate the immediate rise of blood glucose concentration. GLYCOGEN STORAGE DISEASES- genetically linked disorders that involve the enzymes regulating glycogen metabolism\ -SYMPTOMS: vary & may include **[muscle cramps and wasting, enlarged liver, and low BSL]** (Blood Sugar Level) -Accumulation of abnormal metabolic byproducts can damage the kidneys and other organs. GLYCOGEN STORAGE DISEASES \[\] HORMONES THAT REGULATE BLOOD SUGAR LEVEL 1. **INSULIN. (**Pancreatic B-cells**)-** enhance entry of glucose into the liver, muscle and adipose tissues.\ - Anti-production of glucose 2. **GLUCAGON. (**Pancreatic a-cells**)**- promotes hepatic glycogenolysis (immediate breakdown of glycogen into glucose) and gluconeogenesis.\ - glucose is produced. 3. **SOMATOSTATIN. (**Pancreatic Delta cells**)-** inhibits secretion of insulin and glucagon.\ - modulates the reciprocal relationship of glucagon and insulin.\ - Inhibits GH (Growth Hormone/Somatotropic hormone) Release that is produced in the anterior pituitary gland. 4. **GROWTH HORMONE/SOMATOTROPIC HORMONE (**Anterior Pituitary Gland**)\ -** Antagonist to insulin, so it produces glucose through lipolysis\ - Stimulates lipolysis(Gluconeogenesis) 5. **THROXINE/ TETRAIODOTHYRONINE (**Thyroid Glands**)-\ -** Stimulates glycogenolysis and the rate of gastric emptying and intestinal\ absorption of glucose. 6. **CORTISOL AND CORTICOSTEROIDS: (**Zona fasciculata- adrenal cortex**)\ **-produced by chromaffin cells\ - Stimulates gluconeogenesis\ - Our stress hormones. The more stressed, the more stimulation of hormones is needed. -Antagonist of insulin as well. 7\. **EPINEPHRINE AND NOREPINEPHRINE (CATECHOLAMINE): (**Chromaffin cells of Adrenal Medulla**).** \- promotes both liver and skeletal glycogenolysis \- Physical or emotional stress cause increase production of epinephrine causing an\ immediate production of glucose for energy. (FIGHT OR FLIGHT)\ - adrenaline rush due to epinephrine 8\. **HUMAN PLACENTAL LACTOGEN (hPL)/ HUMAN CHORIONIC SOMATOMAMMOTROPIN-** pregnant people**\ -** With anti-insulin activity= sudden increase of blood sugar in women.\ - gestational diabetes 9\. **ACTH- ADRENOCORTICOTROPIC HORMONE (**Anterior Pituitary**)\ - w/** anti-insulin activity- produces glucose\ 10. **SOMATOMEDINS (**Liver**)\ - w/** insulin-like activity= promotes entry of glucose into the cell so glucose will be utilized. **IMMEDIATE EFFECTS IN INCREASE BloodGlucoseLevels** **- Physiologic increase in the uptake of glucose by the liver and brain cells\ - increase release of insulin\ - increase uptake of glucose by peripheral tissues\ - inhibition of glucagon release**