Integration of Metabolism

Question 1

Metabolic features of the brain

Answer 1

Requires continuous supply Cannot metabolise fatty acids Ketone bodies can partially substitute Too little glucose (hypoglycemia) faintness and coma Too much glucose (hyperglycemia) irreversible damage for retina

Question 2

Metabolic features of tissue

Answer 2

ATP depending on exercise Reliant on carbohydrate and fatty acid oxidation Light contraction - OxPhos Vigorous contraction - 02 becomes limiting factor, glycogen breakdown and lactate formation

Question 3

Metabolic features of heart

Answer 3

Aerobic respiration - mitochondria Can use TCA cycle substrate - free fatty acids, keton bodies

Question 4

Metabolic features of tissues

Answer 4

Wide repertoire of metabolic process Highly metabolic Maintaining blood glucose Glucose storage organ Lipoprotein metabolism Transport of triglycerides and cholesterol

Question 5

Metabolic features of adipose tissue

Answer 5

Long term storage site for fatty acids in the form of triglycerides

Question 6

Glycolysis

Answer 6

Excess glucose-6-phosphate can be used to generate glycogen

Excess Acetyl CoA can generate fatty acids

During fasting acetyl CoA results in ketone body production rather than TCA cycle
Glucose-6-phosphate undergos pentose phosphate pathway which generates the bulk of NADPH

Question 7

How do avoid a hypoglycaemic coma

Answer 7

Breakdown of liver glycogen

Release free fatty acids

Convert acetyl CoA into ketone bodies via the liver

Question 8

Gluconeogenesis

Answer 8

Lactate generated by skeletal muscle which can be taken up by the liver and using lactate dehydrogenase

Amino acids can be from diet or from skeletal muscles

Glycerol backbone used genertes dihydroxyyacetone phosphate DHAP

Red arrows indicate which key steps must be bypassed

Question 9

What are the irreversible reactions of glycolysis

Answer 9

Kinase hexokinase

Phosphofructokinase

Pyruvate kinase

Question 10

Bypass reactions of gluconeogenesis

Answer 10

It is not energetically favourable

Additional high energy bonds required

Question 11

Overview of glycolysis

Answer 11

Question 12

Can fatty acids be converted into glucose by gluconeogenesis

Answer 12

No

Instead they can be converted into ketone bodies

Question 13

Aerobic respiration

Answer 13

Increase in glucose demands result in increase in the number of glucose transporters

Increase in requirement of muscle actomyosin ATPase and cation balance

Adrenalin plays a key role: increase glugoneogenesis, glycolysis and release of fatty acids

Question 14

Anaerobic respiration

Answer 14

To replenish NAD+ levels and maintain glycolysis, pyruvate is taken up by the liver and converted in lactate

Lactate is then used to generate glucose by gluconeogenesis

Question 15

How do we control metabolic pathways

Answer 15

Centred around irreversible steps

Can be by product inhibition

Under influence of signalling molecules such as hormones

Question 16

What is the michaelis constant

Answer 16

Km which is the concentration of substrate which an enzyme functions at half-maximal rate

Question 17

What does a low Km mean for hexokinase 1 (found in muscle)

Answer 17

Active at low concentrations and operating at maximal velocity

Highly sensitive to inhibition of glucose-6-phosphate

When TCA stops accumalates glucose-6-phosphate

Question 18

What does a higher Km in Hexokinase 4 meane (found in liver)

Answer 18

Less sensitive to blodo glucose concentrations and less sensitive to inhibitory effects of glucose 6 phosphate

Glucose 6-phosphatase can catalyse the reverse reaction

Question 19

When is insulin secreted

Answer 19

Blood glucose levels rise

Question 20

When is glucagon released

Answer 20

Glucose levels fall

Question 21

When is adrenalin released

Answer 21

Strong and fast metabolic effects to mobilise fight or flight

Question 22

When are glucocorticoids used

Answer 22

Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability

Question 23

What effect does having a meal have

Answer 23

Increase glucose uptake by liver used for glycogen and glycolysis (acetyl coa used for fatty acid synthesis

Increase glucose uptake and glycogen synthesis

Increased triglyceride synthesis in adipose tissue

Increase usage of metabolic intermediates due to general stimulatory effect

Question 24

After a meal what happens

Answer 24

Blood glucose falls

Increased glucagon secretion

Glucose production in liver results from glycogen breakdown and gluconeogenesis

Utilisation of fatty acid breakdown as alternative substrate

Question 25

What happens after prolonged fasting

Answer 25

Adipose tissue hydrolyse triglycerid

TCA cycle reduced to provite substrate for glucogneogenesis

Protein breakdown for amino acids for gluconeogenesis

Ketone bodies are produced from fatty acids and amino acids liver to substitute partially for brains requirement for glucose

Question 26

What is Type 1 diabetes

Answer 26

Individuals fail to secrete enough insulin (B-cell dysfunction)

Question 27

What is Type 2 diabetes

Answer 27

Individuals fail to respond appropriately to insulin levels

Question 28

What are complications of diabetes

Answer 28

Hyperglycaemia

Increase in plasma fatty acids and lipoproteins levels with possible cardiovascular complications

Increase in ketone bodies with risk of acidosis

Hypoglycaemia if insulin dosage is imperfectly controlled

Question 29

Why is glucagon important in protection against hypoglycaemia

Answer 29

Stimulates gluconeogensis as glycogenolysis