Integration of Metabolism

Question 1

What fuel sources do muscles rely on during vigorous contraction

Answer 1

Carbohydrates and fatty acid oxidation

Question 2

How much of resting metabolic rate is used by the brain and nervous tissue, despite making up 2% of body weight What fuel source can it utilise

Answer 2

20% Glucose only, ketone bodies partially

Question 3

What % of body weight do these tissues make up: Muscle Brain and nervous tissue Adipose tissue Heart Liver

Answer 3

Muscle 40% Brain and nervous tissue 2% Adipose tissue 15% Heart 1% Liver 2.5%

Question 4

What % of resting metabolic rate is made up by a) liver b) heart

Answer 4

A 20% B 10%

Question 5

During fasting, what is the fate of much of the Acetyl CoA produced

Answer 5

Ketone body formation (rather than entering the tca cycle)

Question 6

What other molecules can be produced from Peruvate and TCA cycle intermediates

Answer 6

Amino acids Backbones can be used to make nucleotides

Question 7

What pathway does glucose-6-phosphate enter for nucleotide production What is generated in bulk by this pathway

Answer 7

Pentose phosphate pathway NADPH for anabolic pathways eg cholesterol synthesis

Question 8

What happens if plasma glucose conc falls below 3mM, eg during fasting

Answer 8

Hypoglycaemic coma

Question 9

What does the body do to avoid hypoglycaemia

Answer 9

Breakdown of liver glycogen stores Release of free fatty acids from adipose tissue Convert Acetyl CoA into ketone bodies via the liver

Question 10

How many hours does it take to typically exhaust glycogen stores

Answer 10

12-18 hrs

Question 11

What is the overall aim of gluconeogenesis What precursors enter this pathway

Answer 11

Generate glucose from pyruvate Non carbohydrate precursors eg lactate, some amino acids and glycerol form pyruvate, oxaloacetate and DHAP respectively

Question 12

What is the fate of lactate in the liver

Answer 12

Converted into pyruvate by lactate dehydrogenase (LDH), aka the Cori Cycle

Question 13

What is the glycerol backbone used to generate in times of starvation

Answer 13

Dihydroxyacetone phosphate (DHAP) Also made in step 5 of glycolysis

Question 14

What steps in the gluconeogenesis pathway are bypassed by non-glycolytic enzymes

Answer 14

Pyruvate(3C) to oxaloacetate (4C) Oxaloacetate(4C) to phosphoenol pyruvate (3C) Fructose-1,6-bisphosphate (6C) to fructose-6-phosphate (6C) Glucose-6-phosphate to glucose

Question 15

Why do three reactions have to be bypassed in gluconeogenesis

Answer 15

Glycolysis has 3 irreversible reactions catalysed by hexokinase, phosphofructokinase and pyruvate kinase. Gluconeogenesis is therefore not a simple reversal of glycolysis as these 3 reactions have to be bypassed

Question 16

Where does gluconeogenesis occur

Answer 16

In the cytoplasm, APART FROM first reaction (pyruvate to oxaloacetate, catalysed by pyruvate carboxylase)

Question 17

How many atp molecules are used up in gluconeogenesis and why

Answer 17

4 ATP Needed to make the reaction energetically favourable

Question 18

What type of amino acids can give rise to glucose via gluconeogenesis following deamination What type of amino acids can be used to synthesise fatty acids and ketone bodies

Answer 18

Glucogenic Ketogenic

Question 19

Why can’t fatty acids be converted into glucose

Answer 19

In the TCA cycle, oxaloacetate is eventually regenerated so no net synthesis of oxaloacetate or pyruvate is possible from Acetyl CoA

Question 20

What 3 enzymes require ATPduring muscle contraction

Answer 20

Muscle actomyosin ATPase Ca2+ATPase Na+K+ATPase for cation balance

Question 21

What role does Adrenalin play in meeting ATP demand

Answer 21

Increases rate of glycolysis in muscle and gluconeogenesis in liver Increases release of fatty acids from adipocytes

Question 22

How does the body respond to an increased demand for ATP, eg during aerobic exercise

Answer 22

Increases number of glucose transporters on membranes of muscle cells Adrenalin

Question 23

How does the body respond when transport of glucose cannot be matched by demand during a aerobic exercise

Answer 23

Increased breakdown of muscle glycogen Liver uses lactate to form glucose (recovery)

Question 24

Name two methods of control of metabolic pathways

Answer 24

Product inhibition Signalling molecules eg hormones

Question 25

What is the difference between the isoforms of hexokinase

Answer 25

They are maximally active at different concentrations of glucose They have a different Michaelis constant (Km) - conc of substrate at which an enzyme functions at a half-maximal rate (Vmax)

Question 26

How does muscle Hk differ from Liver Hk

Answer 26

Muscle Hk (Hk I): High glucose affinity (Km of 0.1mM) High sensitivity to glucose 6 phosphate inhibition Liver Hk (Hk IV): Low glucose affinity (Km of 4mM) Less sensitive to G6P inhibition

Question 27

What enzyme in the liver catalysed the reverse reaction to hexokinase

Answer 27

Glucose-6-phosphatase

Question 28

What are glucocorticoids

Answer 28

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

Question 29

How does insulin affect the body

Answer 29

Secreted from islets of pancreas Increased glucose uptake by liver - used for glycogenesis and glycolysis (Acetyl CoA needed for fatty acid synthesis) Increased glucose uptake and glycogenesis in muscle Increased triglyceride synthesis in adipose tissue Increased usage of metabolic intermediates (due to general stimulatory effect on body’s synth and growth)

Question 30

How does the body respond to falling blood glucose levels

Answer 30

Inc glucagon and red insulin secretion Glucose production in liver from glycogenolysis and gluconeogenesis Fatty acids breakdown utilised for atp production (preserves glucose for brain) (Similar to adrenaline)

Question 31

How does the body react to prolonged fasting (longer than can be covered by glycogen reserves)

Answer 31

Glucagon/insulin ratio increases further Adipose tissue hydrolysed triglycerides to provide fatty acids for metabolism Tca cycle intermediates reduced to provide substrates for gluconeogenesis Protein breakdown provides aa substrates for gluconeogenesis Ketone bodies produced from fa and as in liver to partially substitute brains glucose req

Question 32

In what condition is metabolism controlled as if the body is undergoing starvation

Answer 32

Diabetes Mellitus (Both B cell dysfunction and insulin resistance)

Question 33

What are some complications of diabetes

Answer 33

Hyperglycaemia with progressive tissue damage (eg retina, kidney, peripheral nerves) Increase in plasma fatty acids and lipoprotein levels, with possible cardiovascular complications Increase in ketone bodies with risk of acidosis Hypoglycaemia with coma if insulin dosage is I perfectly controlled

Question 34

How does insulin deficiency and relative excess of glucagon affect the liver

Answer 34

Increased hepatic output of glucose and thus, hyperglycaemia