SOURCES OF ENERGY
CARBOHYDRATES
 stored as glycogen
 glycogen provides short term fuel reserve (~ 24 hrs)
 mainly stored in liver: ~ 24 hr supply for export (note: kidney also contributes to
glycogen reserves)
 muscle: small reserve for own use
 Neurons: no glycogen stores, glycogen in glial cells
 excess carbohydrate not needed for immediate use is stored as glycogen or TAGs
FATS
 stored as TAGs in adipocytes
 long term fuel reserve (~ 3 months depending on individual fat stores)
 liver: preferred fuel; synthesis of FA for export in form of VLDL muscle:
preferred fuel of resting muscle
 Adipocytes: store TAGs, FA are preferred fuel, export FA
 brain: cannot use FA because they do not cross BBB, can adapt to ketone bodies
PROTEIN: significant source of energy only after prolonged fasting or activity (eg
marathon)
 muscle: major source
 liver: minor source, uses amino acid "skeletons" for gluconeogenesis, NH4+
detoxification via urea cycle
Fuel
glycogen
 signal
 tissue
Fat
 signal
 tissue
Protein
 signal
 tissue
Feeding
synthesis
insulin
L,M,K
synthesis
insulin
A, L
synthesis
insulin
various
fasting
mobilization
glucagon
L (K)
mobilization
glucagon
A
increased
degradation
starvation
depletion
mobilization
glucagon
A
continued, but
somewhat
reduced,
degradation
excitement
mobilization
adrenalin
L, M
mobilization
adrenalin
A
little or no
degradation
Tissue
fuel reserve
preferred fuel
fuel exported
Brain
none
none
Skeletal muscle
glycogen
(P-creatine)
glucose
(ketone bodies)
strictly aerobic
fatty acids: aerobic
glucose during
vigorous activityanaerobic
hormone recep
lactate
alanine (fasting,
excessive activity)
adrenalin, insulin
heart muscle
glycogen
(P-creatine)
none
adrenalin
insulin
fat cells
TAGs
fatty acids
(glucose, ketone
bodies)
strictly aerobic
fatty acids: aerobic
liver
glycogen
fatty acids
fatty acids
glycerol
glucose
fatty acids
adrenalin
insulin
adrenalin
glucagon
insulin
Brain:
Fuel reserve: essentially none (small glycogen store in some
non-neuronal cells)
Metabolism: strictly aerobic
Preferred fuel: glucose (obligatory), uses ketone bodies during
prolonged fast, can use lactic acid
Fuel exported: none

High respiratory rate. Accounts for ~ 20% of bodies oxygen
consumption in adult.

Glucose is an obligate metabolic fuel. Brain utilizes about
120g glucose a day.

Because brain does not synthesis or store glycogen it is
dependent on a continuous supply of glucose from
circulation.

Under normal of elevated blood [glucose] rate of blood-tobrain transfer exceeds rate of brain glucose metabolism. At
low blood [glucose], blood-to-brain transfer becomes
limiting.

Can adapt to use of ketone bodies during fast (note: long
chain FA cannot cross blood brain barrier and cannot be
used as fuel by brain) but still require carbohydrates. KB
may account for as much as 60% of fuel after prolonged
fast.
Skeletal muscle:
Fuel reserve: glycogen (P-creatine)
Metabolism: at rest or during prolonged activity - aerobic
short, vigorous activity - glycolytic
Preferred fuel: fatty acids, glucose during vigorous activity
Fuel exported: lactate, alanine
Hormones: insulin, adrenalin

accounts for ~ 30% of O2 consumption at rest. This may
increase to as much as 90% during vigorous exercise.

At rest - aerobic metabolism, preferred fuels are FFA, also
glucose and ketone bodies.

effects of exercise
 short, vigorous (eg 100 M sprint)
 fueled by P-creatine and glycolytic ATP
 in 10 sec. sprint muscle P-creatine decreases from 9.1
to 2.6 mM, and ATP from 5.2 to 3.7 mM (what is the
effect of this on glycolytic rate?). Blood lactate
increases from 1.6 to 8.3 mM and blood pH decreases
from 7.42 to 7.24. Acidosis causes fatigue.
 longer (eg, 1000 M run)
 aerobic energy, oxidation of muscle glycogen - energy
produced at a slower rate so pace is slower (see table
below).
 very long periods of exercise (eg marathon)
 uses liver as well as muscle glycogen supply - even
slower rate of energy production. Muscle and liver
glycogen combined are insufficient to provide fuel
required for marathon (require about 150 mols ATP,
muscle and liver glycogen provide at most about 105
mols). Difference made up from fat reserves - but
this is even slower rate of energy production so pace
slow further. (Elite runners stretch out glycogen
supply and can maintain faster pace longer. )
Heart muscle:
Fuel reserves: glycogen (P-creatine)
Metabolism: strictly aerobic
Preferred fuel: fatty acids, also uses ketone bodies and glucose
Fuel exported: none
Hormones: insulin, adrenalin
Adipose tissue:
Fuel reserve: TAGs, some glycogen
Metabolism: aerobic
Preferred fuel: fatty acids, also uses glucose
Fuel exported: fatty acids, glycerol
Hormones: insulin, adrenalin

TAGs may account for as much as 65% of weight of fat cell.

FFAs bind to serum albumin for transport in serum.

receives exogenous TAGs in chylomicron from intestinal
system (note: these travel to circulation via lymphatic
system and largely bypass liver)

high bld glucose - glucose used for FA and TAG synthesis
 requires source of glucose to make TAGS (lacks glycerol
kinase)
Liver:
Fuel reserve: glycogen
Fuel exported: glucose, fatty acids (VLDLs)
Metabolism: aerobic
Preferred fuel: fatty acids, also uses glucose
Hormones: insulin, adrenalin, glucagon
Other roles: N detoxification and export of urea, synthesis of
serum proteins, synthesis of bile acids,
cholesterol (incorporated into VLDLs)

critical in maintenance of glucose homeostasis

most incoming nutrients are delivered to liver via the portal
vein (chylomicron are the exception) where they are
processed to fuels and precursors for other tissues.

glucose sensors: high Km GluT2, high Km glucokinase,
phosphorylase kinase

fasting state: glycogenolytic/gluconeogenic/lipolytic
fed state: glycogenesis/glycolytic/lipogenic

 Metabolism



of fats
used for local P-lipids
FFA are major oxidative fuel for liver
synthesis of ketone bodies when CHO are limiting
and there is large mobilization of TAGs from
adipose tissue.

AcCoA used for synthesis of FA, cholesterol

synthesizes lipoproteins and forms VLDL for
delivery of fats to other tissues.
 amino



acids
high protein diet - amino acids are used for the
synthesis of liver proteins and the majority of serum
proteins, including albumin. (Low serum albumin
levels is diagnostic of liver pathology.) They are also
catabolized to provide precursors for
gluconeogenesis and for energy production via the
TCA cycle.

detoxifies N through formation of urea.

high CHO/low protein - most amino acids pass
through because of high Km of catabolic enzymes
for amino acids.
carbohydrate
stores CHO as glycogen and exports glucose derived from
glycogen and from gluconeogenesis
Red blood cell
Fuel reserve: none
Metabolism: anerobic
Preferred fuel: glucose (obligatory)
Fuel exported: lactic acid

formation of 2, 3 bis-phosphoglycerate for maintenance of
low affinity form of haemoglobin

role of HMPS in maintaining NADPH and reduced
glutathione
Kidney

role in N metabolism: secretion of NH4+, urea
 during kidney disease N end products (urea, creatinine,
uric acid) accumulate. High CHO diet with amino
acids limited to essential amino acids may help regulate
this - liver can synthesize non-essential amino acids.

secretion of excess ketone bodies

some gluconeogenic activity - eg from glutamine via ketoglutarate

acid-base regulation: excess H+ secreted as NH4+, during
acidosis renal activity for the production of NH4+ increases
( NH4+ , gluconeogenesis) and urea production by liver
decreases. During alkalosis liver urea production increases
and renal NH4+ secretion and gluconeogenesis decreases.
Intestine

small intestine: preferred fuel - glutamine

colon: preferred fuel : short chain fatty acids produced by
bacteria from unabsorbed foods. Excess short chain FA not
used by colonocytes pass to portal vein for use by liver.
 colonocytes also produce ketone bodies that are released
into portal vein for use by extrahepatic tissues