A&P: Metabolism 2 Quiz

Glucose Metabolism

• Glycogenesis is the storage of glucose
• Glycogenesis involves insulin stimulating hepatocytes and skeletal muscle cells to synthesize glycogen
• Glycogen is a polysaccharide, is the only stored carbohydrate in humans, and is formed when many glucose molecules combine
• The body stores approximately 500g of glycogen, with 75% in skeletal muscle
• Glycogenolysis is the release of glucose
• Glycogenolysis is stimulated by glucagon and epinephrine
• Glycogen stored in hepatocytes is broken down into glucose and released into the blood
• Glycogen stored in muscle is converted to glucose-6-phosphate, then enters glycolysis
• Skeletal muscle lacks the enzyme to cleave the final phosphate in glycogen stored in muscle
• Gluconeogenesis is the formation of glucose from non-carbohydrate sources
• Gluconeogenesis takes place in the liver
• Gluconeogenesis is stimulated by cortisol and glucagon
• Substances like glycerol, lactic acid, and most amino acids can be used in gluconeogenesis

Lipid Transport

• Lipids are transported by lipoproteins
• Lipoproteins are spherical with an outer shell of proteins called apoproteins, phospholipids, and cholesterol surrounding fats
• Lipoproteins render nonpolar and hydrophobic lipids more water-soluble
• Apoproteins in the outer shell of lipoproteins each have specific functions and are transport vehicles
• Lipoproteins are categorized and named according to density: the ratio of lipids to proteins
• High density lipoproteins have more proteins
• Examples of lipoproteins include: chylomicrons, very low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs)
• Chylomicrons transport dietary lipids and are formed in small intestine mucosal epithelial cells
• Chylomicrons enter villi and eventually lacteal to be carried by lymph into venous blood
• Chylomicrons transport dietary lipids to skeletal muscle, cardiac muscle, adipose tissue, and the liver
• Very low-density lipoproteins (VLDLs) are formed in hepatocytes and transport triglycerides to adipocytes
• VLDLs become LDLs once triglycerides are removed
• Low-density lipoproteins (LDLs) carry 75% of total cholesterol in the blood
• “Bad cholesterol" is the term for LDLs
• LDLs deliver to body cells for repair of cell membranes and synthesis of steroid hormones
• Excess LDLs deposit cholesterol in and around smooth muscle in arteries, forming fatty plaques and increasing the risk of coronary artery disease
• High-density lipoproteins (HDLs) are considered the "good cholesterol"
• HDLs act to remove excess cholesterol from body cells and blood and deliver it to the liver for elimination in bile salts
• HDL prevents the accumulation of cholesterol in the blood, linking a high HDL level with a decreased risk of coronary artery disease

Cholesterol Sources and Health Applications

• Cholesterol has 2 sources: food, which does not have a large impact, and endogenous production by the liver
• Endogenously produced cholesterol is impacted mostly by trans and saturated fats
• Indicators of potential cardiovascular problems are total cholesterol above 200 milligrams/deciLiter and a high LDL:HDL ratio
• Excess cholesterol accumulation as plaques in blood vessels can cause hypertension, heart attacks, and strokes

Lipid Catabolism - Lipolysis

• Lipolysis is the breakdown of lipids
• Lipids are broken down into pieces that can be converted to pyruvate or channeled directly into the citric acid cycle, either route generates ATP
• If the demand for energy is low, triglycerides are stored in adipocytes
• Triglycerides consist of glycerol and 3 fatty acids, which each can generate ATP
• Breakdown must occur for muscle, liver, and adipose tissue to oxidize fatty acids for ATP
• Lipolysis is enhanced by epinephrine, norepinephrine, cortisol, and thyroid hormones, while insulin inhibits lipolysis
• Glycerol is converted to glyceraldehyde 3-phosphate and then to pyruvate, yielding 2 ATP
• Fatty acids are catabolized to acetyl-CoA through beta-oxidation in the mitochondrial matrix
• Both pyruvate and acetyl-CoA can enter the Citric Acid Cycle
• An enzymatic reaction breaks off the first two carbons as acetyl-CoA
• For each step in beta-oxidation, the cell gains 13 ATP where the process is repeated until the entire fatty acid is broken down
• beta-oxidation produces more ATP per carbon than glucose
• Excessive beta oxidation with a lack of glucose results in the formation of ketones in the liver
• Heart, brain, and RBCs use ketone bodies to generate ATP, but brain and RBCs rely on it since they cannot use beta oxidation
• Excessive ketones can lead to ketosis and/or ketoacidosis, of which the latter damages tissue
• Lipid catabolism/beta-oxidation is useful because it is very efficient and excess lipids can be easily stored as triglycerides
• Lipid catabolism/beta-oxidation cannot provide large amounts of ATP quickly
• Lipid catabolism/beta-oxidation is well suited for chronic energy demands during stress or starvation
• Water-soluble enzymes struggle to access the insoluble droplets during lipid catabolism

Lipid Anabolism - Lipogenesis

• Lipogenesis is when liver and adipose cells synthesize lipids
• Lipogenesis begins with acetyl-CoA, where almost any organic substrate can be converted to acetyl-CoA
• Lipogenesis occurs when more calories are consumed than needed for ATP production, so dietary carbs, protein, and fats are all converted to triglycerides
• Essential fatty acids (linolenic acid and linoleic acid) cannot be synthesized and must be obtained from the diet

Protein Metabolism

• Amino acids can be oxidized to produce ATP or used to synthesize new proteins
• Excess dietary amino acids are not excreted
• Excess dietary amino acids are converted into glucose via gluconeogenesis, or triglycerides via lipogenesis
• Protein from worn-out cells is recycled where they may be converted to other amino acids, reformed to make new proteins, or enter CAC
• Before entering CAC, the amine group must be removed via deamination in hepatocytes
• Various points exist for which amino acids enter the Krebs cycle for oxidation
• Deamination produces ammonia, and the liver converts to urea for excretion in urine
• Protein synthesis is carried out using ribosomes via translation using free amino acids
• Essential amino acids cannot be synthesized in the body and need to be acquired via diet
• Nonessential amino acids can be synthesized
• Nine essential amino acids exist in humans
• Complete proteins contain sufficient amounts of all essential amino acids, such as beef, fish, poultry, and eggs
• Incomplete proteins do not contain all essential amino acids, such as leafy green vegetables, legumes, and grains
• Eleven other nonessential amino acids can be synthesized by body cells using amination and transamination
• Transamination is transfer of amine group from one amino acid to a ketoacid to form a new amino acid

Metabolic Adaptations - Absorptive State

• In the absorptive state, ingested nutrients are entering blood stream and glucose is available for ATP production
• During the absorptive state, effects of insulin dominate
• In the postabsorptive state, absorption of nutrients from stomach contents is complete
• During the postabsorptive state, energy needs are met by stored fuels in the body
• Nervous system and red blood cells depend on glucose which means maintaining steady blood glucose is critical during postabsorptive state

Absorptive and Postabsorptive State Characteristics

• The absorptive state occurs when nutrient absorption is taking place
• The absorptive state typically continues for ~ 4 hours, and insulin is the primary regulating hormone
• Insulin stimulates glucose uptake and glycogenesis, amino acid uptake and protein synthesis, and triglyceride synthesis
• Glycolysis and aerobic metabolism provide the ATP needed to power cellular activities as well as the synthesis of lipids and proteins
• Storage of excess fuel molecules takes place in hepatocytes, adipocytes, and skeletal muscle cells
• The postabsorptive state begins ~ 4 hours after the last meal when absorption in the small intestine is nearly complete
• Blood glucose levels start to fall during the postabsorptive state
• During the postabsorptive state, metabolic activity focuses on mobilizing energy reserves and maintaining blood glucose between 80-120 mg/dL
• Several hormones coordinate the postabsorptive state, like glucagon, epinephrine, glucocorticoids, and growth hormone
• Glucocorticoids stimulate the mobilization of lipid and protein reserves and these effects are enhanced by growth hormone
• Glucagon stimulates glycogenolysis and gluconeogenesis which stabilizes blood glucose levels since it is primarily in the liver and releases of glucose by the liver
• Epinephrine stimulates glycogenolysis in skeletal and cardiac muscle, and lipolysis in adipocytes

Overall Goals of the Postabsorptive State

• Produce more glucose by breakingdown liver glycogen and through lipolysis, and gluconeogenesis using lactic acid, glycerol, and/or amino acids
• Conserve blood glucose through oxidation of fatty acids, lactic acid, amino acids, ketone bodies and breakdown of muscle glycogen
• Blood lipid and amino acid levels decrease during the postabsorptive state
• Catabolism of lipids and amino acids in the liver will produce Acetyl-CoA which leads to the formation of ketone bodies
• Ketone bodies diffuse into blood, and is an alternative means used by other cells as their source for energy from outside their own lipids and amino acids

Fasting and Starvation

• Fasting is going without food for many hours or a few days
• Starvation implies weeks or months of food deprivation or inadequate food intake
• During fasting and starvation, nervous tissue and RBCs continue to use glucose for ATP production
• A dramatic metabolic change that occurs during fasting and starvation is the increase in formation of ketone bodies by hepatocytes from excess fatty acid metabolism
• Ketones become used as an alternative fuel source during fasting and starvation