Energy Metabolism and Metabolic Adaptation

Question 1

What are the different fuel sources for energy metabolism?

Answer 1

Starch/Glycogen source of glucose
Fat or Triacylglycerol source of fatty acids and glycerol
Proteins source of amino acids

Question 2

What are the main catabolic pathways in the body?

Answer 2

Glycolysis
PDC and the Citric Acid Cycle
Oxidative Phosphorylation
Fatty Acid Oxidation
Amino Acid Catabolism

Question 3

What does the Liver specialize in for metabolic activity?

Answer 3

Chemistry capital of the body. Capable of catabolism and anabolism ( of glucose, fat, amino acids)

Responsible for maintaining proper glucose concentration in the body, managing the storage and distribution of excess fuel, the synthesis of glucose from non-carbohydrate presursors (gluconeogenesis) in extreme circumstances, and the detoxification of waste like Ammonia

Question 4

What do the kidneys specialize in?

Answer 4

The Urea cycle as well as amino acid catabolism.

Question 5

What do muscles specialize in?

Answer 5

fuel includes glycogen, glucose, Triacylglycerol (fat), and ketone bodies. (amino acids in extreme circumstances)

Capable of anaerobic catabolism of glucose, generating a quick burst of energy due to glycolysis and lactic fermentation. (The lactate produced causes muscle fatigue and decrease of pH.)

Muscle stores phosphocreatine as emergency energy stock

Question 6

What is the Cori Cycle?

Answer 6

The process in which Lactate is transported to the Liver via blood and undergoes gluconeogenesis to be converted into Glucose. This then gets transported back to the muscles

Question 7

What does the Brain specialize in?

Answer 7

Very active in Oxidative Phosphorylation

Prefers glucose as a fuel source but can use ketone bodies in extreme circumstances

Catabolic pathways include glycolysis, Citric Acid Cycle, and oxidative phosphorylation

Brain has little to no glycogen storage. Too low levels of Glucose can cause brain dysfunction and coma. Extended period of low glucose (hypoglycemia) in blood may cause irreversible damage to the brain or even death.

Question 8

What does Adipose Tissue specialize in?

Answer 8

These tissues are widely distributed around the body. Predominantly around the abdominal cavity and upper part of limbs/thighs.

These tissues store and release fatty acids as required, insulates the body, protects from physical damage, and beautification (good complexion)

Normal fat storage is sufficient to meet bodies energy requirements for 3 months

Question 9

How is fuel stored in the body?

Answer 9

For a 70kg man, the body has:
- 15kg of stored fat (Triglycerides) in adipose tissues that should last for about 3 months
- 6kg of Muscle which can last for about 20 days
- Glycogen in the muscle and liver would last for less than a day

Question 10

Where and how is glucose synthesized in the body?

Answer 10

Can be made via gluconeogenesis of the following:
- Pyruvate
- Amino Acid Carbon Skeleton
- Glycerol part of triglycerides (fat)

Question 11

How are fatty acids produced in the body?

Answer 11

Fatty acids are produced via Acetyl-CoA
This CANNOT be used for gluconeogenesis. Instead, it is used to make ketone bodies which circulates as fuel in muscle and brain

Question 12

How does the body adapt to prolonged starvation?

Answer 12

Prolonged starvation leads to depletion of oxaloacetate in the liver which means the CAC stops running. Acetyl-CoA is converted into ketone bodies and the brain adapts to use them.

• After 40 hours, 96% of glucose produced in the liver is done via gluconegenesis
• After 3 days, 30% of the brains energy needs are fulfilled by ketone bodies
• After 40 days starvation, 70% of the braisn energy is fulfilled by ketone bodies

Question 13

What are the differences between the two types of diabetes?

Answer 13

Type 1 is Insulin dependant (or Juvenile onset diabetes)- There is an absence of insulin in the body, which leads to defective B-cells, and autoimmune destruction.

Type 2 is Non-Insulin Dependant or Maturity onset diabetes. Involves a deficiency of Insulin RECEPTORS. ~90% of diagnosed cases. Also referred to as Insulin-Resistant DIabetes

Question 14

How does Insulin work?

Answer 14

Insulin binds to Insulin receptors, which then promotes the uptake of glucose from the blood into tissues.

In diabetes, insulin-stimulated glucose entry is blocked

Question 15

What two enzymes catabolize alcohol in the liver while drinking?

Answer 15

1. Alcohol Dehydrogenase - Converts ethanol to acetaldehyde using NAD+ as oxidizing agent, producing NADH
2. Aldehyde Dehydrogenase - Oxidizes acetaldehyde into into acetate using NAD+, also producing NADH

Question 16

What causes Liver cirrhosis?

Answer 16

Excess drinking leads to excess NADH produced, which leads to the accumulation of fat produced in the liver. This causes hyperlipidemia aka Fatty Liver.

Excess fat limits the CAC, which causes Hypoglycemia

Hypoglycemia accelerates lactate dehydrogenase to produce lactic acid which leads to Hyperlacticacidemia

Question 17

What happens when the body has too high of blood glucose levels?

Answer 17

It spills over in urine which then depletes tissues of necessary glucose.
This means that in tissues, Triacylglycerol (fat) Hydrolysis, Gluconeogenesis, ketone body formation, and Fatty Acid Oxidation all increase. This causes KETOSIS

Question 18

What is Ketosis?

Answer 18

High level of ketone bodies in the body.
Causes increases acidity which creates problems with buffering of blood pH. This leads to an excretion of H+, which causes dehydration and excessive thirst.

Question 19

What causes Maturity Onset Diabetes of the Young (MODY)?

Answer 19

A mutation in Glucokinase.
Glucokinase is responsible for coordinating insulin release with glucose levels

Question 20

What is Gestational Diabetes?

Answer 20

Affects 2-5% of Women during pregnancy.
Excess of glucose in moms blood -> Excess sugar being fed to the fetus. The sugar turns to fat and the baby becomes obese while still in the uterus.

Gestational Diabetes goes away after birth

Question 21

What causes Gestational Diabetes?

Answer 21

Hormonal changes during pregnancy causes reduced response of body cells to insulin (receptor problem)

Estrogen, Cortisol, and Human Placental Lactogen all block the effect of insulin. Known as the “Cotrainsulin Effect”

Question 22

What is Obesity?

Answer 22

• Fatty acids stored as triacylglycerol as preferred fuel source
• Excess dietary fatty acids stored
• Excess carbohydrates metabolize into Acetyl-CoA which convert into fat which is then stored

Question 23

What causes obesity?

Answer 23

• Inefficient fuel consumption
• Defective appetite control may lead to imbalance between consumption and storage

Question 24

Is there an obesity gene?

Answer 24

Yes. a gene was discovered that encoded a protein called “Leptin”. It is produced by adipocytes.
In mice, the injection of Leptin in obese mice caused weight loss and loss of appetite, meaning leptin plays a major role in catabolism.

Question 25

What is Neuropeptide Y and how does it affect hunger?

Answer 25

The decrease of availability of Leptin in the brain causes the secretion of Neuropeptide Y from the Hypothalamus in the brain.
Neuropeptide Y stimulates appetite and promotes insulin secretion

Question 26

How is human obesity affected by Leptin?

Answer 26

In human obesity, there is no deficiency of Leptin production. However, there may be defects with Leptin receptors in the brain or problems with the blood-brain barrier which can limit the access of leptin to the hypothalamus.

The exact mechanism has yet to be discovered nut may cause a cure for human obesity.