22 Metabolism under special conditions Flashcards
Which cells cannot use fatty acids as a fuel source?
- RBCs
- Brain
- CNS
Roughly how many kg in a 70kg man is made up of fat?
10-15kg
What are the 3 fuel sources (other than glucose and fatty acids) which are available under special conditions?
eg starvation
-
Amino acids
- Breakdown muscle proteins
- Converted to:
- Glucose
- Ketone bodies
-
Ketone bodies
- From fatty acids
- Used when glucose=critically short
- Brain can metabolise instead of glucose
-
Lactate
- Anaerobic metabolism-muscle
- Liver uses Cori cycle - converts lactate back to glucose
- Used as fuel source for TCA cycle
Give examples of 2 amino acids which are:
Glucogenic:
Ketogenic:
Both:
- Glucogenic: Alanine, Valine
- Ketogenic: Lysine, Leucine
- Both: Tyrosine, Phenyalanine
Which of the following hormones are anabolic and which are catabolic?
- Glucagon
- Insulin
- Growth Hormone
- Adrenaline
- Cortisol
- Thyroid Hormones
-
Anabolic:
- Insulin
- Growth Hormone (increased protein synthesis)
-
Catabolic:
- Growth Hormone (increased lipolysis and gluconeogenesis)
- Adrenaline
- Cortisol
- Thyroid Hormones
- Glucagon
What processes does Insulin suppress/inhibit? (5)
- Gluconeogenesis
- Glycogenolysis
- Lipolysis
- Ketogenesis
- Proteolysis
What processes does insulin promote? (4)
- Glucose uptake in muscle and adipose GLUT 4
- Glycolysis
- Glycogen synthesis
- Protein synthesis
How does the body respond to energy starvation?
- Decreased blood glucose
-
Cortisol released from adrenal cortex
- Has anti-insulin effects
- Glucagon released from pancreas
- Stimulate gluconeogenesis
- __Glycerol from fat
- Provides important substrates required
- __Glycerol from fat
- Stimulate break down of fat
- Reduced insulin
- Cells use fatty acids preferentially over glucose
-
Liver produces ketone bodies
- Brain starts to utilise these
- Kidney’s contribute to gluconeogenesis
- Fat stores depleted- protein=fuel
Why should those that have been starved for a prolonged period of time only gradually increase the protein in their diet?
REFEEDING SYNDROME
Enzymes of urea cycle have been down regulated
What is the approximate net weight gain by the mother during pregnancy?
Approx. 8kg
When does the majority of fetal growth occur (2/3) during pregnancy?
- Last 1/3 of pregnancy
- 28 weeks onwards
What are the 2 main phases of metabolic adaptation during pregnancy?
- Anabolic phase
- Catabolic phase
What does the anabolic state involve?
(during pregnancy)
- Increase maternal fat stores
-
Small increase in level of insulin sensitivity
- Promotes anabolic state
Nutrients= stored to meet future demands of rapid fetal growth in late gestation and lactation after birth
What does the catabolic state involve?
- Decreased insulin sensitivity (increased resistance)
- Maternal glucose increases
- Free fatty acid concentration increases
=greater substrate availability for fetal growth
- Delayed maternal disposal of nutrients after meals
- Placenta secretes anti-insulin hormones at fast rate
How is glucose (the prinicipal fuel for a fetus) transported via the placenta?
Simple diffusion via GLUT 1
What effect does the fetus have on maternal metabolism?
Controls maternal metabolism to ensure its own survival
What are the components of the new endocrine entity known as the fetoplacental unit?
- Placenta
- Fetal adrenal glands
- Fetal liver
Placenta secretes proteins- controlling maternal hypothaloamic pituitary axis
Name some hormones which are released by the placenta
What hormones does the placenta secrete which exert an anti-insulin effect on maternal metabolism?
- Corticotropin releasing hormone
- Human placental lactogen
- Progesterone
- Likely for:*
- Transient hyperglycaemia to occur after meals*
- Hypoglycaemia between meals*
What happens to the pancreatic beta cells during pregnancy?
Oestrogen and progesterone causes:
hypertrophy and hyperplasia of pancreatic beta cells
Increased sensitivity to blood glucose
Increased insulin secretion and synthesis
What might cause gestational diabetes to occur?
Beta cells not responding normally to changes during pregnancy
Define gestational diabetes
Disease- pancreatic beta cells do not produce sufficient insulin to meet increased requirement in late pregnancy
What are the 3 underlying causes of gestational diabetes?
- Auto antibodies (similar to type 1) - less than 10% cases
- Genetic susceptibilty (Rare 1-5%)
- Beta cell dysfunction in setting of obesity and chronic insulin resistance (evolving type 2) (Majority of cases)
What % of pregnancies are affected by gestational diabetes?
3-10%
What effects/complications can gestational diabetes have?
- Increased incidence of miscarriage
- Increased incidence (4x) of congential malformation
- Fetal macrosomia
- Increased risk of shoulder dystocia (shoulders stuck during birth)
- Associated with hypertensive disorders: preeclampsia (high BP and damage to liver/kidneys)
What condition are women with gestational diabetes more likely to develop later in life?
Type 2 diabetes
Identify 5 risk factors for gestational diabetes.
- Maternal age >25yrs
- BMI >25 kg/m2
- Race/ethnicity (more common asian, black, hispanic)
- Personal/family history of diabetes
- Family history of macrosomia
How is gestational diabetes managed?
- Dietary modification
- Insulin injections
- Regular ultrasound scan- assess fetal growth and wellbeing
What molecule is present in muscles to provide immediate energy and rapdily replenish ATP levels?
Creatine phosphate (Only enough for about 5 secs of energy in 100m sprint)
Name the 2 processes which supply ATP during exercise?
- Glycolysis
- Oxidative phosphorylation
Outline the process by which muscle glycogen is used to provide energy.
Via which transporters do muscles take up blood glucose?
GLUT4 transporter: insulin promotes translocation to plasma membrane
GLUT1 transporter: constitutively active
Apart from the insulin dependent process, how else does exercisng muslce increase its glucose uptake?
Increase AMP stimulates AMPK
AMPK cause signalling cascade
GLUT4 translocation increases
Fatty acids can only be used as fuel under aerobic conditions. What is their capacity limited by?
Uptake across mitochodrial membrane via carnitine shuttle
Ouline the use of energy sources during exercise
Outline the hormonal control response to prolonged exercise
- Insulin falls- inhibited by adrenaline
- Glucagon rises
- Adrenaline and GH rise
- Cortisol rises slowly
