BMS2021 Lecture Notes - Lecture 12: Renal Medulla, Lysosome, Cytosol

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Week 5. Metabolism in fasting and starvation
Portal vein carries nutrients to liver
Hepatocytes turn nutrients into fuel
Hepatoyte ezyes tu oe uikly do’t last log, degaded ito aio aids ad used as
fuel, recycled)
Liver
o Unique features:
-GLUT2 transporter
-glucokinase (hexokinase IV) ; not inhibited by G-6-P
o G-6-P fates:
-dephosphorylated into free glucose
-make into glycogen
-glycolysis -> acetyl coA then ATP or fatty acids and TAG
-pentose phosphate pathway to yield NADH and R-5-P
o Amino acid fate:
-made into proteins for liver (eg. albumin)
-bloodstream for other tissues
-hormones/nucleotides
-CAC intermediates/pyruvate -> GNG
o Fatty acid fates:
-primary fuel for liver a’t ete ai, oud to seu alui
-excess acetyl coA -> ketone bodies
-some acetyl coA -> cholesterol
-FA to phospholipids
-FA to TAGs for storage
transferred to lipoproteins to carry FA to heart and muscle for oxidation
o Ketone body:
- from acetyl coA
-made when oxaloacetate pools are insufficient
-can enter brain unlike FA
-released by liver to bloodstream
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Fat tissue
o White adipose tissue (WAT)
- fuel storage
-large adipocytes filled with one lipid droplet
-little mitochondria
o Brown adipose tissue (BAT)
-for thermogenesis
-smaller adipocytes with several lipid droplets
-more mitochondria (more cytochrome/iron -> brown)
Hae this he e’e o, eas use this duig hieatio to geeate heat
Adipocytes
o Carry out glycolysis through oxphosphorylation
o Use FA to make TAGs
-from intestinal lipids via chylomicrons
-from liver via very long dense lipids (VLDL)
o Release FA when other tissues need them eg. skeletal muscle, heart
Muscles
o Slow twitch (red muscle):
-rich in mitochondria
-provide energy via slow and steady oxphosphorylation
o Fast twitch (white muscle):
-fewer mitochondria and lower oxygen
-uses ATP faster and fatigues faster due to greater demands
o Heart:
-more mitochondria
-fuelled by FA (some ketone, glucose, phosphocreatines)
-use oxphosphorylation (dependent on oxygen)
o Use glycolysis when active (not getting enough oxygen) -> lactate -> cleaved out
in liver, recycled back to glucose
o Phosphocreatine; ADP -> ATP (small bursts of ATP), high energy molecule
Tissues for which blood glucose is essential:
o RBC do’t hae itohodia, use ATP via glycolysis)
o Bone marrow
o Renal medulla
o Peripheral nerves
Epinephrine = fight flight (we need energy now)
Glucagon = we are out of glucose
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Well-fed state vs starvation:
Well-fed state
o Lipogenic liver
-fats can go through lymphatic system
Starvation
o Glucogenic liver
o Gluconeogenesis:
-high Km
-low blood glucose = increased gluconeogenesis
-high blood glucose = decreased gluconeogenesis
o Muscle protein degradation:
-amino acids can degrade to pyruvate -> transaminate to alanine -> blood ->
liver -> pyruvate -> glucose ->back in blood
o Last resort for fuel in fasting
o Early starvation:
-increased ketones
-acetoacetate -> acetone -> out of breath (alcohol like smell)
-increased acetoacetate and B-hydroxybutyrate lower blood pH dangerously
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Document Summary

Metabolism in fasting and starvation: portal vein carries nutrients to liver, hepatocytes turn nutrients into fuel, hepato(cid:272)yte e(cid:374)zy(cid:373)es tu(cid:396)(cid:374) o(cid:448)e(cid:396) (cid:395)ui(cid:272)kly (cid:894)do(cid:374)"t last lo(cid:374)g, deg(cid:396)aded i(cid:374)to a(cid:373)i(cid:374)o a(cid:272)ids a(cid:374)d used as fuel, recycled) Glucokinase (hexokinase iv) ; not inhibited by g-6-p: g-6-p fates: Glycolysis -> acetyl coa then atp or fatty acids and tag. Pentose phosphate pathway to yield nadh and r-5-p: amino acid fate: Cac intermediates/pyruvate -> gng: fatty acid fates: Primary fuel for liver (cid:894)(cid:272)a(cid:374)"t e(cid:374)te(cid:396) (cid:271)(cid:396)ai(cid:374), (cid:271)ou(cid:374)d to se(cid:396)u(cid:373) al(cid:271)u(cid:373)i(cid:374)(cid:895) Fa to tags for storage transferred to lipoproteins to carry fa to heart and muscle for oxidation: ketone body: Ha(cid:448)e this (cid:449)he(cid:374) (cid:449)e"(cid:396)e (cid:271)o(cid:396)(cid:374), (cid:271)ea(cid:396)s use this du(cid:396)i(cid:374)g hi(cid:271)e(cid:396)(cid:374)atio(cid:374) to ge(cid:374)e(cid:396)ate heat. Adipocytes: carry out glycolysis through oxphosphorylation, use fa to make tags. From liver via very long dense lipids (vldl) Muscles: release fa when other tissues need them eg. skeletal muscle, heart, slow twitch (red muscle):

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