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Lecture 25

BIOCHEM 4M03 Lecture Notes - Lecture 25: Insulin-Like Growth Factor 2, Glycogenesis, Birth Weight


Department
Biochemistry
Course Code
BIOCHEM 4M03
Professor
Deborah Sloboda
Lecture
25

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Biochem 4M03 – Lecture 25 - Early life metabolic regulation III
- Don’t confuse placental lactogen with lactate (sometihg like that)
Fetal Growth and Metabolism
- Regulators of fetal growth:
oGenetics, nutrition, endocrine  fetus
Fetal Growth is not linear
-Growth in humans
-Pretty slow in first bit then rises rapidly then tends to plateau off at end
oFetus now huge at end so providing its own constraint
Birth weight poor indicator of growth pattern
-Draw this graph (above right) when she asks why birth weight is not good reflection of
growth pattern
oDescribe 3 babies grow at different rates that end up at same birth weight
Fetus  “glucose dependent parasite”
-Remember the fetus is anabolic
-Because it’s anabolic, all enzymes favour deposition (energy storage)
-Fetal enzymes favour: Glycogenesis glu glycogen
oGlucose is preferred fuel of fetus
oLactate is number two
-Lipogenesis fatty acid synthetase pathway  adipose
oDe novo synthesis from acetyl CoA
-Protein synthesis
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oMost essential and non-essential amino acids are transported across placenta
-Fetal glucose utilization rates > neonate or adult
-Placenta has high capacity to uptake and transport glucose
oGLUT1 and 3
oRapid transport, gradient, to fetus
-How to we maintain steep gradient
oFetal glucose levels < maternal, favours a constant gradient to fetus
-High shunting of glucose (a lot goes to placenta, some converted to lactate)
Fetal Glucose levels: hepatic gluconeogenesis is LOW
-Postnatal hepatic gluconeogenesis
oNon glucose sources
oNon carbohydrate sources and lactate
oMaintained in liver and muscle
Where does fetal lactate go?
-Study done on sheep looking at rates of different substrates as it goes through fetal liver
oLooked at lactate and amino acids and glucose
oNumbers represent how much of substrate per mole of oxygen uptake (oxidative
metabolism)
-Lactate coming from placenta
-Fetal hepatic gluconeogenesis rates are very low
oThis is an adaptation to maintain that high concentration gradient
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oSo instead, liver produces high amounts of different types of glucogenic
substrates
oMaintains transplacental transfer
-Contrary to what might be predicted from knowledge of postnatal hepatic metabolism
this uptake does not result in the hepatic output of glucose
oResults in the hepatic output of five other glucogenic substrates
-Liver produces high amounts of different types of glucogenic substrates
oNot so much glucose
oEnter as intermediates in TCA cycle
-Not the same as postnatal gluconeogenesis
Fetal hepatic adaption = low gluconeogenesis
-Fetal hepatic pyruvate and glutamate output is part of an adaption to placental function
that requires the fetal liver to maintain both a high rate of catabolism of glucogenic
substrates and a low rate of gluconeogenesis
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