UNC BIOL253 Final Exam Study Guide

Absorptive State

Period when nutrients are being digested an absorbed and there is net synthesis of glycogen, triglyceride, and protein

• Energy provided primarily by absorbed carbohydrate; some carbohydrate used for synthesis of glycogen & fat

• Some energy also provided by fatty acids of absorbed triglycerides; most fatty acids resynthesized into fat in adipose tissue

• Cholesterol absorption and synthesis balanced in part by the liver and lipoproteins; some cholesterol secreted into bile and converted into bile salts

• Absorbed amino acids used to synthesize proteins; excess amino acids used to synthesize carbohydrate & triglycerides

Postabsorptive State

Period when nutrients are no longer being digested or absorbed, and there is net breakdown of glycogen, fat, and protein

• Glucose concentration in blood maintained by hepatic glycogenolysis and gluconeogenesis, and a switch to fatty acid and ketone utilization by most tissues

• Glucose sparing

• The brain continues to use glucose for energy but also starts using ketones as they build up in the blood

Glucose Sparing (also called Fat Utilization)

Most of the body’s energy supply comes from oxidation of fatty acids released by adipose-tissue lipolysis, and from ketones produced by the liver; this spares glucose for the brain and nervous system

Absorbed Carbohydrates

• Glucose = body’s major energy source during absorptive state

• Transformation of glucose to triglycerides in adipocytes

• Absorbed glucose enters cells and is catabolized into CO₂ + H₂O in ATP synthesis

• Skeletal muscle = major consumer of glucose, it also uses some glucose to synthesize glycogen (stored in muscle cells for future use)

• Adipose tissue cells catabolize glucose for energy

3 Major Fates of Glucose During Absorptive State

1. Utilization for energy

2. Storage as glycogen in liver and skeletal muscle

3. Storage as triglyceride in adipose tissue

3 Major Sources of Fatty Acids in Adipose-Tissue Triglyceride

1. Glucose that enters adipose tissue and is broken down to provide building blocks for the synthesis of fatty acids

2. Glucose that is used in the liver to form VLDL triglycerides, which are transported in the blood and taken up by the adipose tissue

3. Ingested triglycerides transported in the blood in chylomicrons and taken up by adipose tissue

Cholesterol

a waxy, fat-like substance produced by the liver and found in every cell, essential for building cell membranes, producing hormones, and creating Vitamin D

• Is a component of plasma membranes and a precursor for bile salts and steroid hormones

Low-density Lipoprotein (LDL)

Known as "bad" cholesterol. High levels can lead to plaque buildup in arteries (atherosclerosis), causing heart attacks or strokes

• Main cholesterol carriers, and they deliver cholesterol to cells throughout the body

• Bind to plasma membrane receptors and are taken up by the cell through endocytosis

High-density Lipoprotein (HDL)

often called "good" cholesterol, as it acts as a scavenger in the bloodstream, transporting excess cholesterol from tissues and blood vessels to the liver to be broken down and removed

• They remove excess cholesterol from blood and tissue, including cholesterol-loaded cells of atherosclerotic plaques

• They then deliver this cholesterol to the liver, which secretes it into the bile or converts it into bile salts

• Deliver cholesterol to steroid-producing endocrine cells

Which main organ controls cholesterol homeostasis?

Liver

Ketones

produced by the body when breaking down fat for energy instead of glucose

Summary of Nutrient Metabolism During the Absorptive State

• Energy is provided primarily by absorbed carbs in a typical meal

• There is net uptake of glucose by the liver

• Some carbs are stored as glycogen in liver and muscle, but most carbs and fats in excess of that used for energy are stored as triglyceride in adipose tissue

• There is some synthesis of body proteins from absorbed amino acids. The remaining amin acids in dietary protein are used for energy or used to synthesize triglycerides

Sources of Blood Glucose

1. Glycogenolysis

2. Lipolysis

3. Protein (a few hours into postabsorptive state)

4. Gluconeogenesis

Summary of Nutrient Metabolism During Postabsorptive State

• Glycogen, fat, and protein synthesis are curtailed, and bet breakdown occurs

• Glucose is formed in the liver both from glycogen stored there and by gluconeogenesis from blood-borne lactate, pyruvate, glycerol, and amino acids (the kidneys also perform gluconeogenesis during a prolonged fast)

• The glucose produced in the liver (and kidneys) is released into the blood, but its utilization for energy is greatly decreased in muscle and other nonneural tissues

• Lipolysis releases adipose-fatty acids into the blood, and the oxidation of these fatty acids by most cells and of ketones produced from them by the liver provides most of the body’s energy supply

• The brain continues to use glucose but also starts using ketones as they build up in the blood

Glycogenolysis

• Location: Occurs primarily in the cytoplasm of liver and muscle cells.

• Liver Function: Liver glycogenolysis releases free glucose into the blood to prevent hypoglycemia, facilitated by the enzyme glucose-6-phosphatase.

• Muscle Function: Muscle glycogenolysis converts glycogen to glucose-6-phosphate, which enters glycolysis directly for muscle energy needs, rather than entering the bloodstream.

• Regulation: Stimulated by glucagon (low blood sugar) and epinephrine (stress/fight-or-flight), which trigger a cAMP-dependent mechanism.

• Significance: It provides an immediate fuel source during fasting or high-intensity exercise.

Lipolysis

the metabolic process of breaking down stored triglycerides into glycerol and free fatty acids through hydrolysis, primarily occurring in adipose tissue

Gluconeogenesis

the metabolic process of synthesizing glucose from non-carbohydrate sources, such as lactate, glycerol, and amino acids, primarily occurring in the liver and kidney cortex. It is essential for maintaining blood sugar levels during fasting, intense exercise, or low-carbohydrate diets, providing energy for brain and red blood cells

Islets of Langerhans

Secretes insulin and glucagon

• Insulin = B cells

• Glucagon = A cells

Insulin

The most important hormone controlling metabolism by acting on:

• Skeletal muscle: stimulates glucose uptake, glycolysis, and net synthesis of glycogen (via activation of glycogen synthase and inhibition of glycogen phosphorylase) and protein

• Adipose tissue: stimulates glucose uptake and net synthesis of triglyceride

• Liver: inhibits gluconeogenesis and glucose release and stimulates net synthesis of glycogen and triglycerides

Secretion is primarily stimulated by an increase in plasma glucose; this effect is amplified by incretins released into the blood from cells of the GI tract

• Secreted by Beta Cells

Counterregulation

The actions of hormones that oppose those of insulin; major stimuli for release include hypoglycemia and the SNS

Glucagon (from islets of Langerhans)

• Stimulates glycogenolysis, gluconeogenesis, and ketone synthesis in the liver

• Secreted by Alpha cells

• Major physiological effects occur within the liver and oppose those of insulin

• Increases plasma concentrations of glucose and ketone, which are important for the postabsorptive state

• Prevents hypoglycemia

• Major stimulus for secretion is a decrease in the circulating concentration of glucose

Epinephrine (from adrenal medulla)

Stimulates glycogenolysis in the liver and muscle, gluconeogenesis in the liver, and lipolysis in adipocytes (via activation of hormone-sensitive lipase)

• Inhibits insulin secretion

• Stimulates glucagon secretion

• Activation of sympathetic nerves to the liver and adipose tissues elicits the same responses from these organs as does circulating epinephrine

Cortisol (from adrenal cortex)

Permissive for gluconeogenesis and lipolysis; in higher concentrations, stimulates gluconeogenesis and blocks glucose uptake

• Presence in the blood maintains the concentrations of the key liver and adipose tissue enzymes required for gluconeogenesis and lipolysis

• Decreases sensitivity of muscle and adipose cells to insulin, which helps to maintain plasma glucose concentration during fasting, sparing glucose for the brain

Growth hormone (from anterior pituitary gland)

Stimulates gluconeogenesis and blocks glucose uptake

• Increases responsiveness of adipocytes to lipolytic stimuli

• Stimulates gluconeogenesis by the liver

• Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue

Hypoglycemia

Abnormally low glucose concentration in the blood; symptoms are similar to those of SNS activation; severe hypoglycemia and lead to brain disfunction and even death if untreated

In skeletal muscles, insulin favors glycogen formation and storage by..?

• Increasing glucose transport into the cell

• Stimulating the key enzyme (glycogen synthase) that catalyzes the rate-limiting step in glycogen synthesis

• Inhibiting the key enzyme (glycogen phosphorylase) that catalyzes glycogen catabolism

For protein synthesis in skeletal muscles, insulin…?

• Increases the number of active plasma membrane transporters for amino acids, thereby increasing amino acid transport into the cells

• Stimulates the ribosomal enzymes that mediate the synthesis of protein from these amino acids

• Inhibits the enzymes that mediate protein catabolism

Major controlling factors for insulin secretion

1. Plasma glucose concentration

2. Increased amino acid concentrations

3. Input of autonomic neurons to the islets of Langerhans

   1. Parasympathetic = increases insulin secretion

   2. Sympathetic = increased plasma epinephrine concentration inhibits insulin secretion

Incretins

Metabolic hormones released after eating to stimulate insulin secretion, lower blood sugar, and promote satiety

• Secreted by enteroendocrine cells in the GI tract in response to eating

• Amplifies the insulin response to glucose

• Glucagon-like peptide 1 (GLP-1)

• Glucose-dependent insulinotropic peptide (GIP)

Hormone-sensitive lipase (HSL)

• In adipocytes, it’s stimulated by the presence of epinephrine

• Once activated, it works along with other enzymes to catalyze breakdown of triglycerides to free fatty acids and glycerol

• Both are then released into the blood, where they serve directly as an energy source (fatty acids) or as a gluconeogenic precursor (glycerol)

• Insulin inhibits its activity during the absorptive state

Effects of Cortisol on Organic Metabolism

1. Basal concentrations are permissive for stimulation of gluconeogenesis and lipolysis in the postabsorptive state

2. Increases plasma concentrations cause:

   1. Increased protein catabolism

   2. Increased gluconeogenesis

   3. Decreased glucose uptake by muscle cells and adipose tissue cells

   4. Increased triglyceride breakdown

3. Net Result = increased plasma concentrations of amino acids, glucose, and free fatty acids

Stress causes…

hormonal changes similar to those caused by exercise

During exercise, the muscles…?

• Use their energy sources plasma glucose, plasma fatty acids, and their own glycogen

• Glucose is provided to the blood by the liver, and fatty acids are provided by adipose tissue lipolysis

• Changes in plasma insulin, glucagon, and epinephrine are similar to those changes that occur during the postabsorptive state and are mediated mainly by the SNS

What happens to the plasma glucose concentration during exercise?

• It changes very little in short-term, mild-to-moderate exercise and may even increase slightly with strenuous, short-term activity due to the counterregulatory actions of hormones

• During prolonged exercise (more than ~90 minutes) the plasms glucose concentration does decreased by usually by less than 25%

• Glucose output by the liver increases approximately in proportion to increased glucose utilization during exercise

What triggers increased glucagon secretions and decreased insulin secretion during exercise?

• One signal during prolonged exercise is the modest decrease in plasma glucose that occurs

• This is the same signal that controls the secretion of these hormones during fasting

• Other inputs at all intensities of exercise include increased circulating epinephrine and increased activity of the sympathetic neurons supplying the pancreatic islets

Effects of Sympathetic Stimulation on Hormones

• Contributes directly to energy mobilization by acting on the liver and adipose tissue

• Contributes indirectly by inhibiting the secretion of insulin and stimulating that of glucagon

What component of the response to exercise is different from fasting?

In exercise, glucose uptake and utilization by the skeletal and cardiac muscles are increased, whereas during fasting they are markedly decreased

How is it that, during exercise, the movement of glucose via facilitated diffusion into skeletal muscle can remain high in the presence of decreased plasma insulin and increased plasma concentrations of cortisol and growth hormone, all of which decrease glucose uptake by skeletal muscle?

Muscle contraction causes migration of an intracellular-store of glucose transporters to the plasma membrane and an increase in synthesis of the transports. For this reason, even though exercising muscles require more glucose than do muscles at rest, less insulin is required to induce glucose transport into muscle cells.