control and integration of metabolism

what are the major organs involved in the metabolism of carbohydrates, proteins, and fat?

liver, adipose cells, skeletal muscle

how do we control the flow of fuels in or out of these tissues?

hormones: insulin, glucagon, epinephrine, norepinephrine, cortisol. growth hormone

autonomic nervous system: para and sympathetic

what does the absorptive state mean?

the state of plenty, occurs when ingested nutrients are being absorbed into the blood

what does the postabsorptive state mean?

the state of fasting, occurs when no nutrients are absorbed from the gastrointestinal system

what is the major goal of the absorptive state?

maintain body proteins and store excess calories as glycogen and fat

how are major energy requirements met during the absorptive state?

via oxidation of glucose

what are the major hormones of the absorptive state?

insulin, growth hormone

how are CHO broken down into monosaccharides?

• salivary amylase breaks down starch into disaccharides (sucrose, lactose, and maltose) and short branched chains of glucose

• Pancreatic amylase digests starch into disaccharides and short branched chains of glucose in the small intestine

• These disaccharides and short chains of glucose are further digested by special brush border enzymes into monosaccharides of glucose, galactose, and fructose

what does SGLT1 do?

co-transports sodium and glucose of galactose into GI epithelial cells

what does GLUT5 do?

transports fructose into the GI epithelial cells

what does GLUT2 do?

transports monosaccharides out of the GI epithelial cells into the interstitial space

what are the body’s cells preferred energy source?

glucose

what does the full oxidation of glucose produce?

ATP, CO2, H2O

what is the main nutrient that stimulates insulin secretion?

glucose

what is insulin?

an anabolic hormone that promotes glucose uptake into skeletal muscle cells and adipocytes through translocation of GLUT4 to the plasma membrane

what are the pathways of glucose in the liver?

• glucose oxidized for energy

• used to synthesize liver glycogen

• metabolized to glycerol 3-phosphate and fatty acids —> triglycerides

what are pathways of glucose in the muscle?

• oxidized for energy

• stored as muscle glycogen

what are pathways of glucose/insulin in adipocytes?

• glucose is oxidized for energy

• glucose is metabolized to glycerol 3-phosphate and fatty acids —> triglycerides

• insulin inhibits lipolysis

what is the role of fat in the body?

• source of energy

• membrane constituent - cell and cell organelles

• precursor for synthesis of hormones

• synthesis of chemical messengers

where does fat digestion and absorption occur?

almost entirely in the small intestine

how is fat digested?

• (in stomach) ingested fat aggregates into large lipid droplets

• the large droplets are emulsified into emulsion droplets

• in the presence of pancreatic lipase, emulsion droplets are converted into fatty acids and monoglycerides

• micelles are formed

• some small amounts of fatty acids and monoglycerides are free in the gut lumen and are in eqm with the fatty acids and monoglycerides carried in micelles

how are large lipid droplets emulsified into emulsion droplets?

through the combined action of mechanical disruption by intestinal motility and by emulsifying agents that include bile salts and phospholipids

what are micelles composed of?

bile salts, fatty acids, monoglycerides, phospholipids, fat soluble vitamins, and cholestrol

how is fat absorped?

• fatty acids and monoglycerides move into the GI epithelial cells

• they are resynthesized into triglycerides and packaged into chylomicrons

• chylomicrons enter the lymphatic vessels and are carried by the lymph to the venous circulation

what is a chylomicron?

a type of lipoprotein particle in which triglycerides are packaged with free and esterfied cholestrol, phospholipids, fat soluble vitamins and coated with amphipathic proteins called apolipoproteins

what happens to fats once they reach the circulation?

lipoprotein lipase (LPL) releases free fatty acids and monoglycerides which can now enter the body’s cells

what are the three sources of fat in adipose cells?

• glucose enter adipocyte and is used for synthesis of triglyceride

• Glucose that entered the liver and was converted to triglycerides, packaged into VLDL, and transported in the circulation. The action of LPL releases free fatty acids and monoglycerides to enter adipocytes and is used in synthesis of triglycerides

• Free fatty acids and monoglycerides (from chylomicrons) enter adipocyte to synthesize triglycerides

what are the different fates of cholestrol in the body?

• stored in the liver

• packaged on VLDL (remnants of VLDL become LDL)

• secreted into bile

• converted to bile salts

what are the different lipoproteins and what are each of their functions?

• chylomicrons: These lipoproteins transport dietary triglycerides and cholesterol from the small intestine to the body’s cells. Lipoprotein lipase (LPL) degrades Chylomicrons to Chylomicron remnants

• VLDL: Very low-density lipoproteins function to transport triglycerides and cholesterol from your liver to the body’s cells (VLDL is precursor for LDL)

• IDL: Intermediate-density lipoproteins are formed from the degradation of VLDL. IDLs can be further degraded to LDLs

• LDL: Low-density lipoproteins carry cholesterol to the body’s cells

• HDL: High-density lipoproteins consist of cholesterol and carry cholesterol back from the tissues and organs to the Liver where the cholesterol will be degraded or recycled

how are proteins digested in the stomach?

• parietal cells secrete HCl

• chief cells secrete pepsinogen, which is converted to pepsin under low pH

• pepsin breaks down proteins into polypeptides

how are proteins digested in the small intestine?

1. the pancreas secretes proteases in their inactive form as zymogens into the pancreatic duct which are then emptied into the small intestine

2. enterokinase convertstrypsinogen into active trypsin —> activate other zymogens

3. trypsin converts chemotrypsinogen into chemotrypsin

4. trypsin converts procarboxypeptidase into carboxypeptidase

5. trypsin and chemotrypsin digest proteins into smaller polypeptides

6. carboxypeptidase split off amino acids from carboxyl ends of peptide fragments

7. brush boarder aminopeptidase split off amino acids from the amino ends of the peptide fragments

8. single amino acids are absorbed into the cytosol of intestinal epithelial cells by sodium-amino acid cotransporters

9. small peptides are absorbed through co-transportation with H+ (which are then broken down into single amino acids by peptidases

10. amino acids cross the basolateral membrance by different specific amino acid transporters into the interstitial space

what is the fate of absorbed amino acids during the absorptive state?

• taken up by cells for protein synthesis

• liver uses ingested amino acids to make proteins and generate energy

• liver uses excess amino acids from diet to synthesize triglycerides

what is the major goal of the postabsorptive state?

to maintain blood glucose levels for the nervous system

what are the major hormones of the postabsorptive state?

glucagon, cortisol, epinephrine, norepinephrine, and growth hormone

what is the main goal of the major hormones of the postabsorptive state?

function to mobilize fuels by the catabolism of CHOs, fats, and proteins and elevate blood glucose

give an overview of what each mechanism must do to maintain blood glucose in the postabsorptive state

• glycogenolysis ++

• gluconeogenesis - -

• keotgenesis ++

• glycolysis - -

• glycogenesis - -

what are sources of blood glucose during the postabsorptive state?

• liver glycogenolysis: glycogen —> glucose

• muscle glycogenolysis: muscle glycogen —> pyruvate or lactate

  • lactate goes to the liver where the liver releases free glucose

• lipolysis: triglycerides are metabolized to glycerol and fatty acids

  • glycerol and fatty acids travel in the blood to the liver where glycerol is used for gluconeogenesis and the fatty acids are used for ketogenesis

• protein catabolism: protein —> amino acids

  • glucogenic amino acids are substrates for gluconeogenesis to produce glucose

  • ketogenic amino acids are utilized for ketogenesis to produce ketone bodies

summarize what happens the postabsorptive state

• liver is in a state of glucose output

• cells, except neurons, switch to oxidation of fatty acids and ketones to provide energy

• protein is catabolized to amino acids to be used by the liver for synthesis of glucose and ketone bodies

Glycogen

Highly branched polysaccharide composed of glucose subunits; major carbohydrate storage form in humans

Glycogenesis

Synthesis of glycogen, predominantly in the liver and skeletal muscle

Glycogenolysis

Breakdown of glycogen to glucose

Gluconeogenesis

Formation of glucose by the liver or kidneys from pyruvate, lactate, glycerol, or amino acids

Glycolysis

Metabolic pathway that breaks down glucose to two molecules of pyruvate (aerobically) or two molecules of lactate (anaerobically). Lipogenesis

Lipolysis

Breakdown of triglycerides

Ketogenesis

Production of ketones, predominantly in the liver

Ketone Body

Any of the three compounds (also called ketones) created by acetyl coenzyme A (acetoacetate, hydroxybutyrate and acetone) which are water-soluble cellular fuels normally exported by the liver. They are products of fatty acid metabolism that accumulates in blood during starvation and in severe untreated diabetes mellitus.

Ketoacid

An acid containing a ketone group in addition to the acid group

Ketoacidosis

Plasma pH < 7.35 accompanied by the accumulation of ketone bodies in the body tissues and fluids.

lipogenesis

synthesis of triglycerides, the primary energetic storage form of lipids