Basic Biochemistry IIBCM301

Chapter 6:Integration, Specialization, and Regulation of

Metabolism

At this point, we’ll consider how organisms arrange/organize the metabolic symphony to meet their energy needs.

Discussion will include how:Body maintains

energy balance (homeostasis)

It deals with starvation

It responds to the loss of control from diabetes mellitus

Biochemistry & nutrition

Table 24-2, p.666

Fig. 24-2, p.668

Food pyramid

Obesity

-Define as weighing at least 20% more than their ideal weight- several inventions: artificial sweeteners, fat substitutes- protein leptin plays a role in the control of obesity

- Has been established in mice- in mice, leptin is 16kDa protein that produced by obesity (ob) gene- mutation in this gene will lead to deficiency of leptin

Organ specialization

Brain

Muscle The Cori Cycle

Liver The Glucose Alanine Cycle

The fate of G6P varies with metabolic requirements – depends on the glucose demandG6P can be converted to glucose by glucose-6-

phosphatase (transport via bloodstream to the peripheral organs)

G6P can be converted to glycogen – when body’s demand for glucose is low

G6P can be converted to acetyl-CoA via glycolysis and action of pyruvate dehydrogenase (this glucose-derived acetyl-CoA used in the synthesis of f.acids)

G6P can be degraded via pentose phosphate pathway (to generate NADPH required for f.acids biosynthesis and liver’s many other biosynthetic functions)

The liver can synthesize or degrade TAGsWhen metabolic fuel is needed, f.acids are degraded to

acetyl-CoA and then to ketone bodies (export via bloodstream to the peripheral tissues)

When the demand is low, f.acids are used to synthesize TAGs (secreted into the bloodstream as VLDL for uptake by adipose tissue)

Amino acids are important metabolic fuelThe liver degrades amino acids to a variety of

intermediates (begin with a.acid transamination to yield α-keto acid, via urea cycle excreted urea)

Glucogenic a.acid – converted to pyruvate / OAA (TCA cycle intermediates)

Ketogenic a.acid – converted to ketone bodies

Kidney

Functions: to filter out the waste product urea from the bloodstream: to concentrate it for excretion: to recover important metabolites (glucose): to maintain the blood pH

Overall reaction in kidney: Glutamine → α-ketoglutarate + NH4

+

During starvation, the α-ketoglutarate enters gluconeogenesis (kidneys generate as much as 50% of the body’s glucose supply)

α-ketoglutarate : converted to malate (TCA cycle) : pyruvate (oxidized to CO2) or via OAA to PEP: converted to glucose via gluconeogenesis

Hormones and second messengers

Fig. 24-5, p.671

Hormones reacts as the intercellular messengersHormones transported from the sites of their synthesis to

the sites of action by the bloodstream

Some typical hormones:

- steroids (estrogens, androgens)

- polypeptides (insulin and endorphins)

- a.acid derivatives (epinephrine and norepinephrine)

Hormones help maintaining homeostasis (the balance of biological activities

Table 24-3, p.672

Fig. 24-7, p.673

Control system mechanism

Hormone releasing factor

Fig. 24-8, p.674

Second messenger e.g cyclic AMP (cAMP)

p.676

Fig. 24-9a, p.675

Fig. 24-9b, p.675

Hormones & metabolism The effects of hormones triggered

the responses within the cell There are three hormones play a

part in the regulation of CHO metabolism

Epinephrine, insulin and glucagon Epinephrine: acts on muscle tissue,

to raise level of glucose on demand, when it binds to specific receptors, it leads to increased level of glucose in blood, increased glycolysis in muscle cells and increased breakdown of f.acid for energy

p.681

Fig. 24-14, p.682

Glucagon: acts on liver, to increase the availability of glucose, when it binds to specific receptors, it leads to increased level of glucose in blood.

Metabolic homeostasis

Table 24-4, p.685

Metabolic adaptation During prolonged starvation, the brain slowly

adapts from the use of glucose as its soul fuel source to the use of ketone bodies, shift the metabolic burden form protein breakdown to fat breakdown

Diabetes mellitus is a disease in which insulin either not secreted or doesn’t stimulate its target tissues → high [glucose] in the blood and urine. Abnormally high production of ketone bodies is one of the most dangerous effects of uncontrolled diabetes