FORM & FUNCTION (Starvation 1)

Question 1

Starvation and obesity

Answer 1

-2 extreme disturbances to energy metabolism
-can occur in all species

Question 2

Stages of starvation

Answer 2

-specific sequence by which body consumes energy sources
>early (glucose)
>intermediate (fatty acid and ketone)
>late (protein

Question 3

Insulin : Glucagon ratio (high insulin)

Answer 3

-increase sugar storages
>glucose uptake and trapping (GLUT4/glucokinase)
>glycogenesis (glycogen synthase)
-increase making fat
>lipogenesis (acetyl-CoA carboxylase): rate-limiting step
>FA transport (lipoprotein lipase)

Question 4

Insulin : Glucagon ratio (high glucagon)

Answer 4

-increase use/make sugar
>glycogenolysis (glycogen phosphorylase)
>gluconeogenesis (PEPCK mRNA levels)
-increase use of fat
>lipolysis (release insulin’s inhibitory effect on HSL)
>ketogenesis (HMG-CoA synthase)

Question 5

Metabolic fate of glucose following a meal:

Answer 5

1. Glucose as endogenous fuel
2. Glycogen storage
3. Fat synthesis

Question 6

Glucose utilization in post-absorption:

Answer 6

glycogen is the first energy source used
-muscle: provide metabolic fuel
-liver: maintain blood glucose
>vital source of energy for the brain

Question 7

Post-absorptive period:

Answer 7

-short
>glycogen storage is only modest

Question 8

64kg mammal glycogen storage:

Answer 8

-liver: 70g (only thing that can be used to increase glucose levels)
-muscle; 286g

Question 9

Resting vs. physical activity energy utilization: (glycogen capacity)

Answer 9

-resting: 21 to 26 kCal/day/kg (about 20 hrs) of body weight
-physical activity (or cold exposure): 70-90 kCal/day/kg (about 6 hours)

Question 10

65kg animal triglyceride storage:

Answer 10

-almost 12kg

Question 11

Fat oxidation: early starvation

Answer 11

-as glycogen depletes, next source is fat
-total fat storage could potentially provide several weeks of survival fuel (20-60days)

Question 12

Early starvation steps:

Answer 12

1. Fat breakdown increases and beta-oxidation becomes the primary source of fuel
2. Gluconeogenesis is increased to support energy for the brain

Question 13

Lipolysis review:

Answer 13

1. Cortisol levels rise in starvation
2. No insulin to inhibit HSL activity
3. Glycerol molecules recycled for gluconeogenesis
4. FFA are shuttle to tissues

Question 14

Gluconeogenesis activation:

Answer 14

-glucose is still needed for brain and RBC
*cannot use the FA
-use glycerol

Question 15

Ketogenesis:

Answer 15

-cells cannot keep up with glucose demand
*must start to synthesize ketones

Question 16

Conditions of ketogenesis:

Answer 16

1. Depletion of CHO (primary metabolic fuel)
2. Activation of FA oxidation to generate ATP
3. BUT, when glucose is low oxaloacetate is used for gluconeogenesis and acetyl-CoA cannot be converted to citrate to enter the TCA
4. Excess acetyl-CoA is shuttled into ketogenesis, which circulate in the blood to feed other tissues

Question 17

Effects of ketone utilization:

Answer 17

*more than 70% of energy requirement non-glucose (ketone bodies and protein)
-ketonemia and ketoacidosis

Question 18

Ketonemia:

Answer 18

-1-2mM (3-4days) to 6-10mM (week 2)
-can lead to ketoacidosis

Question 19

Ketoacidosis

Answer 19

-increased anion gap

Question 20

Starvation insulin : glucagon (high glucagon, low insulin):

Answer 20

-Carbs: decrease glycogen synthase, increase glycogen phosphorylase
-Fat: increase hormone-sensitive lipase, decrease acetyl-CoA carboxylase
-Alternate fuel: increase PEPCK, increase HMG-CoA synthase

Question 21

Sequence of metabolic adjustment in starvation:

Answer 21

-as exogenous glucose decreases, hepatic glycogenolysis increases
>then gluconeogenesis and plasma FFA
*maximal hepatic synthesis of plasma KB at 3-5 days of starvation

Question 22

Starvation complications:

Answer 22

-steatosis
-ketoacidosis

Question 23

Steatosis:

Answer 23

-fatty liver disease
-rate of lipolysis EXCEEDS capacity to use them
-O2 consumption reduced by 10-15% (decreased basal metabolic rate)
-lipolysis rate exceeds aerobic metabolism
-excess FFA re-uptake in the liver, exceeds the rate of export

Question 24

Fatty liver:

Answer 24

-malnutrition impairs VLDL assembly
>protein synthesis requiring ATP is reduced in the liver)
-common in cats (stress, diabetes)
-jaundice

Question 25

Jaundice:

Answer 25

-liver unable to process bilirubin
>bilirubin formed when hemoglobin is breakdown=yellow pigment

Question 26

Ketoacidosis:

Answer 26

*surge of ketone production as alternative source of fuel causes a decrease in HCO3-
-H+ produced removes HCO3- or Cl-
>results in an increased anion gap

Question 27

Consequence of ketoacidosis:

Answer 27

-drop in blood pH leads to metabolic acidosis