Regulation of Metabolism

• How does the body know when to increase metabolism? Slow metabolism?

• What might be some indicators of energy status within the cell?

Requires communication

Works through allosteric regulation of enzyme activity

Figure 6-1 - Overview

Mechanisms of Cellular Communication

Figure 6-2b

Figure 6-2c

Figure 6-2a

What Hormones Regulate Metabolism?

• Insulin

• Glucagon

• Thyroid hormone

• Cortisol

• Epinephrine

Most regulation occurs in order to maintain stable blood glucose concentrations for supplying fuel to the brain!

Figure 6-3

Protein or peptide hormone

Almost always proteins called kinases

Activation/inactivation of an enzyme; opening/closing a membrane channel; activating a transcription factor

Figure 6-4 (2 of 3)

Steroid Hormones(examples: cortisol, testosterone, estrogen

Figure 6-4 (3 of 3)

Protein/peptide hormones

(examples: epinephrine, insulin, glucagon, oxytocin)

Figure 6-5

Figure 6-7

Amplification

What are some advantages to having an amplified signal?

What might be some disadvantages?

Figure 6-8

How is the signal from the hormone (signal molecule) binding to the receptor transmitted into the interior of the cell?

Table 6-1

Table 6-2

Figure 6-10

Insulin works through a tyrosine kinase (TK) receptor mechanism

Insulin from cells of the pancreas

Figure taken from: http://www.smbs.buffalo.edu/bch/Courses/bch404/GW_Nature_InsulinSig.pdf#search=%22GLUT4%20vesicles%20micrograph%22

Insulin regulation of glucose entry in skeletal muscle

*Overall insulin promotes storage of glucose as a fuel and a reduction of blood glucose when elevated

Insulin regulation of glucose metabolism in the liver

Figure taken from: http://www.smbs.buffalo.edu/bch/Courses/bch404/GW_Nature_InsulinSig.pdf#search=%22GLUT4%20vesicles%20micrograph%22

Figure taken from: http://www.smbs.buffalo.edu/bch/Courses/bch404/GW_Nature_InsulinSig.pdf#search=%22GLUT4%20vesicles%20micrograph%22

Major Effects of Insulin

• Skeletal muscle takes up glucose from blood• Liver takes up glucose, increases glycogen

production• Liver increases fatty acid synthesis when its

glycogen stores are full• Adipose takes up blood glucose and fatty acid

breakdown is inhibited

Overall insulin has a fat sparing action. It works to store excess energy

Figure 6-11 - Overview

Mechanism of action for glucagonGlucagon from cells of pancreas

Figure from: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/glucagon.html

Major effects of glucagon:

• Stimulates breakdown of glycogen stored in the liver

• Activates hepatic gluconeogenesis (using amino acids and other non-carbohydrate precursors)

Overall the effects of glucagon are to increase blood glucose when it is low

Lactate from muscle

(Cori Cycle)

Glucogenic amino acids

Figure taken from: http://web.indstate.edu/thcme/mwking/gluconeogenesis.html

Figure taken from: http://web.indstate.edu/thcme/mwking/gluconeogenesis.html

Figure 6-12 - Overview

Thyroid releasing hormone/Thyroid stimulating hormone/Thyroid hormoneHypothalamus Anterior pituitary Thyroid

gland

Figure taken from: http://www.nature.com/ncpendmet/journal/v1/n1/fig_tab/ncpendmet0020_F1.html

• Increased metabolic rate and heat production

• Increased fat mobilization

• Increased carbohydrate metabolism

Figure 6-15

Epinephrine works on cells via Ca2+ as a second messenger

• Increases glycogenolysis and gluconeogenesis

• Increases release of glucagon and cortisol

Phosphorylation of glycogen phosphorylase; increases breakdown of glycogen in liver

Epinephrine can also work via the cAMP signal transduction pathway

Test Your Knowledge

• The major hormones that promote glucose release into the blood are:

• The major hormones that promote storage of glucose are:

• A hepatic cell has receptors for epinephrine, glucagon, and insulin. These hormones may or may not act in concert to produce a desired effect. How does the hepatocyte know what to do?

• What are the major second messenger systems used by the hormones that regulate blood glucose? What is the end result of activation of these second messenger systems?

Figure 6-14

Figure 6-16

Figure 6-17

Table 6-3

Table 6-5