SHEET L.01 SLIDE 1 (Carbohdrates) 2017 Page 1|7 SHEET L.01 SLIDE 1 (Carbohdrates) 2017 *Carbohydrate : When we talk about carbohydrates the first thing that comes to mind is (sugar) (glucose). -The major energy source inside our body is glucose, so the first thing we’ll discuss is glucose metabolism. *What are the sources of glucose in our body ? I-Diet: Amount of carbohydrate in food will be digested and absorbed and some will be converted to glucose . II- Gluconeogenesis: Gluco = glucose Neo = new Genesis = synthesis synthesis of new glucose . The most important organ in gluconeogenesis is the liver (because the enzymes needed are more abundant in the liver) so basically gluconeogenesis happens in the liver . *what are the precursors for the synthesis of glucose ? A-Lactate Lactate comes from lactic acid (pH dependant) from anaerobic glycolysis . [normally in our body the glucose is used by aerobic glycolysis that forms acetyl co-A, which enters the citric acid cycle (krebs cycle) and gives energy as an end product], but sometimes when we have low amounts of O2 reaching the tissue, as in exercising, then part of the energy will be produced by anaerobic glycolysis and lactic acid will be produced, which can be utilized in glucose synthesis. B-Amino Acids Not all of them but some of them can be be used in glucose synthesis, by using the carbon skeleton of amino acids to produce glucose. BUT when does the body produce glucose by this way ? 1-In starvation b/c no energy from diet is received so our body tries to synthesize glucose by different pathways some of them is through amino acids (also from proteins, mainly muscular proteins). 2- When we are eating large amounts of amino acids that is not needed by the body ( We don't have a place to store the amino acids so the body tries to utilize it) , the amino acids will be converted to glucose . C-Lipids -Lipids are basically cholesterol and triglycerides . -triglycerides = glycerol + fatty acid Page 2|7 SHEET L.01 SLIDE 1 (Carbohdrates) 2017 *fatty acids as it is, can not be used to synthesize glucose but glycerol can be used ,WHY? b/c there is a reversible reaction, which turns excess glucose( energy) to fatty acids. * A + B + C all are gluconeogenesis . III- Glycogenolysis : Glycogen = is a polymer of glucose monomers, and basically glycogen is the storage of glucose inside the body . Glycogen is mainly stored inside our body in the liver and muscles ( muscles only stores glycogen for its own use, on the other hand the glycogen stored in the liver is for the whole body). -When the concentration of glucose is low, the glycogen will be broken down ( by glycogenolysis) so glucose will be produced . As a summary there are three main sources of glucose in our body ( diet , gluconeogenesis ,and glycogenolysis ). These three processes do not occur at the same time ( if I'm well nourished then there is no need to produce glucose or breakdown glycogen, but If I’m not getting any glucose from diet then glycogen will be the primary source of glucose then after a certain limit of starvation, our bodies produce glucose through gluconeogenesis). Glucose is a very important molecule that has major roles so it should be kept within normal levels; [ 70180 ] mg/dL 70 mg/dL is the fasting glucose level and 180 mg/dL is the post prandial . These numbers are so important b/c, fasting blood glucose should be between 70-100 mg/dL (the normal range) this is not a diagnosis for a disease. Whereas after the meals levels will be up to 180 (doesn’t exceed). So normally shouldn’t go below 70 mg/dL or above 180 mg/dL . Hormones; mainly " insulin" are responsible for regulating the glucose levels. Insulin is the only hormone that is released as a response to hyperglycemia (high levels of glucose) it action is to store glucose and prevent further elevation in glucose levels above 180 mg/dL. Now, the important question why 180 mg/dL ?! • 180 = renal threshold (usually the body tries to conserve glucose b/c its important so whatever we have we shouldn’t lose it we must store it) so glucose will be filtered through renal system and then will be reabsorbed again and usually the transporters can transport up to 180 mg/dL , any further levels that exceeded that glucose will be lost in urine (this is what happens in DM). If we are eating high amounts of glucose then it will be stored as glycogen, and if the concentrations are too high then it will be used to synthesize TG and Fatty acids . لو ما بصير هيك كان ما نصحنا لما ناكل سكر و حلويات. Page 3|7 SHEET L.01 SLIDE 1 (Carbohdrates) 2017 So again glucose is very important molecule and our body make sure not to lose it . So what determined that 180 mg/dL is the renal threshold? What determined that below 70 mg/dL is called hypoglycemia? -The importance of the 70 mg/dL level is for the brain In our bodies there are organs that only use the glucose as their source of energy (can't use fatty acid) such as the brain WHY ? 1. In the brain we can’t store glycogen WHY?! b/c it needs space to be stored due to its large size. Glucose is hydrophilic and it must be stored with water molecules to be stabilized , so it's stored as a polymer of 100 glycogen together to avoid affecting the osmotic pressure. Whereas lipids didn't need water to be stored in the brain and they collapsed together to form hydrophobic droplets. 2. Glucose is the only major source of energy for the brain b/c fatty acids need special enzymes for their breakdown, also the entry of F.A into the brain tissue is difficult. 3. Entry of glucose into the brain is not insulin dependent. * Glucose entry to brain is via transporter (facilitated diffusion) and the driving force is concentration gradient. When glucose levels are below 70 mg/dL, there's no concentration gradient, so the brain can't do the extraction of glucose normally. Hence, the brain can't synthesize glucose(lack of enzymes). -The brain can't store glucose in large amounts. -The brain uses glucose as a major source to produce energy. -Extraction concentration gradient dependant. Is the glucose the only source of energy for the brain ? The answer is no, b/c we have what is called ketone bodies which can be used by the brain (metabolized) through mitochondria as an energy source. *The parts that don’t have mitochondria such as (RBC'S, Retina of the eye) can't use ketone bodies. The energy sources for the brain are: glucose + ketone bodies BUT glucose is the primary source . So again glucose is so important molecule and we must conserve it and keep it within normal limits which is 70-180 mg/dL (below 180 to avoid losing it in urine and above 70 for the brain to maintain conc. gradient and the other organs that can’t utilize other than glucose as a source of energy ). *Why RBC'S don’t have mitochondria ? To ensure a very efficient transportation of O2 so it contain mainly hemoglobin in a high percentage . Page 4|7 SHEET L.01 SLIDE 1 (Carbohdrates) 2017 Our bodies synthesize RBC'S with nuclei and mitochondria at the beginning then with time the RBC'S will get rid of all organelles and only keep hemoglobin to carry O2 as much as possible . What are the major hormones that are responsible for regulation of glucose levels ? The primary one is insulin, insulin is released as a response of hyperglycemia as we said before and has major functions to do and many sites to target such as : Increase glycogen synthesis, decrease glucose synthesis, inhibit the glycogenolysis, and increase the entry of glucose to cells "via transporters" to be stored as a form of fat . Inside our bodies the entry of glucose to any cell is directed by the concentration gradient driving force. Normally the intracellular concentration of glucose is lower than the extracellular concentration because the intracellular glucose is utilized immediately, BUT some organs have transporters that can be affected by insulin, so when we have an increase in the levels of glucose it will enter cells by the influence of insulin to be stored . This process doesn’t occur in the brain (if it did happen then we should have insulin all the time to allow entry of glucose to the brain and if glucose levels in the body decrease, insulin will not be produced, and glucose can’t enter the brain); thus the brain entry of glucose is insulin independent . *The full effects of insulin (to reduce glucose levels) is shown in a figure in slide 4. -Potassium entry to cells is stimulated by insulin as well b/c entry of glucose is co-transported with potassium . *Other hormones that regulate glucose are : glucagon, cortisol, growth hormone. *(insulin is the only one released as a response of hyperglycemia, the other hormones are released as response to hypoglycemia) Glucose levels that we see are a result of the interplay of insulin and other hormones trying to keep glucose level balanced between 70-180 mg/dL . And any abnormalities in these hormones will result in abnormal glucose levels and will eventually lead to diseases such as DM. *Diabetes mellitus : Types: • Type 1 DM • Type 2 DM Type 1 DM : form 10-15% of DM cases, usually occur at an early age but also occurs in adulthood. The patient usually is lean, in this type the insulin secretion is little to none due to destruction of beta cells (Cells responsible for insulin secretion) , so insulin therapy is needed for survival in this type. There are different hypotheses about the cause of this destruction such as autoimmune disease, viral infection, or genetics. (but until now there's no specific gene responsible for DM) . Page 5|7 SHEET L.01 SLIDE 1 (Carbohdrates) 2017 BUT having T1DM didn’t necessarily mean other family members will be affected so because of that the genetic factor in T1DM is not clear yet. Type 2 DM : form 80-90% of DM cases, usually related to adults but also happens in children. The patient is usually obese. In this type the insulin secretion is normal to high but the cellular response to insulin is reduced (sensitivity), so we need an agent that increase sensitivity such as biguanides, sulfonylurea….etc, it's also affected by genetics. *We can't control our genes, so having a family history of DM should encourage us to change our lifestyle (less sugar , more exercise ……etc) In the case of family history of breast cancer(female) or colon cancer(male) we should do more frequent screening (mammogram,tests,……etc). *At the end it’s important to distinguish between T1DM and T2DM and the differences between them and to understand the complications of each one. *hypoglycemia is below 70 mg/dL , and hypoglycemia >>>>>> more dangerous than hyperglycemia because the hyper can be controlled but hypo complications are faster and can cause death . Page 6|7 SHEET L.01 SLIDE 1 (Carbohdrates) 2017 في نهاية كل يوم سوا ًء كان جيدا ً أم سيئا ً تعَهد بان تبذل ً جهدا ً أفضل غدا Dina Al-ezz Seema Shalabi Rawan abu-odeh Baraah Alshorman Sahar ALazzam Page 7|7
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