Metabolism

Definitions
§ Metabolism : all chemical reactions necessary to maintain life
§ Cellular respiration : food fuels are broken down within cells and some of the
energy is captured to produce ATP
§ Anabolic reactions :synthesis of larger molecules from smaller ones (ex
making proteins from amino acids)
§ Catabolic reactions : hydrolysis of complex structures into simpler ones (ex:
breakdown of proteins into amino acids)

1
 What happens to the food you eat? 2
Processed in three major stages Stage 1: GI Tract

Stage 1:
Nutrients are: PROTEINS CARBOHYDRATES FATS
• Digested into absorbable units.
• Absorbed into the blood and Amino acids Glucose and other sugars Glycerol Fatty acids

transported to tissue cells. Stage 2: Tissue Cells

Glucose
Proteins Glycogen Triglycerides
Stage 2:

Glycolysis
Anabolism or catabolism:
•In anabolism, nutrients are built NH3 Pyruvic acid

into macromolecules. Stage 3: Mitochondria

CO2

•In catabolism, nutrients are broken Acetyl CoA

down to pyruvic acid and acetyl

CoA. Citric
acid
•Glycolysis is the major Infrequent cycle CO2

catabolic pathway. O2

H Oxidative phosphorylation
H2 O
Stage 3: (in electron transport chain)

Oxidative breakdown of stage 2 Catabolic reactions

products to form ATP Anabolic reactions
ATP ATP ATP
1. Carbohydrate Metabolism Stimulates glucose
uptake by cells
Blood glucose levels rise after you eat.
Insulin regulates blood glucose levels
Insulin Tissue cells
Stimulates
glycogen
formation
Pancreas
Glucose Glycogen

Blood glucose
Liver
falls to normal
range.
Stimulus IMB
A LA
• Blood glucose levels NC
increase E Normal blood glucose level (about 90 mg/
BALANCE: 100 ml)
Carbohydrate Metabolism

• Insulin Regulates Blood Glucose Levels

1. Insulin binds to receptors on cells

• All cells except brain, liver, RBCs have insulin receptors
2. This opens the glucose channel on the cell and glucose enters the cell
What happens to glucose once it enters a cell?

Glucose can be
• Converted to ATP
• Stored as glycogen in the liver and the
muscle
• converted to fat in adipose tissues

Adipocytes
store extra
All of these lower blood glucose levels
carbs as fat
 When blood glucose levels are low
IMB
AL
AN
CE
BALANCE: Normal blood glucose level (about 90 mg/100 ml)

IMB
AL
AN Stimulus
CE
Blood
glucose level
Blood Glucose rises to
normal range.

Pancreas

Glucose Glycogen

Liver
Stimulates Glucagon
glycogen
breakdown
Homeostatic Imbalance: not enough insulin produced

Hyposecretion of insulin results in diabetes

Type 1: pancreatic bet-cells can't make insulin

• Insulin injection

Type 2: insulin made by pancreas but cells are largely unresponsive to insulin
• Exercise
• Weight loss
• Healthy diet
• Metformin
Carbohydrate Metabolism, cont.
§ Oxidation of glucose is shown by the overall reaction:
C6H12O6 + 6O2 à 6H2O + 6CO2 + 36 ATP + heat

§ Glucose is catabolized in three pathways

§ Glycolysis: Glucose to pyruvic acid
§ Citric acid cycle (CAC): Pyruvic acid to acetyl-Coa to make products
§ The electron transport chain and oxidative phosphorylation: use the
products make in CAC and make ATP 8
1. Glycolysis: Glucose

2 ATP

• Location: Occurs in the cytosol 2 ADP

• Anaerobic: Does not need Oxygen to

Fructose-1,6-
bisphosphate
P P

breakdown glucose

• Starting molecule: Dihydroxyacetone

phosphate
Glyceraldehyde
3-phosphate
P P
2 Pi
2 NAD+

• Ending molecule: Makes 2 pyruvic Acids 4 ADP

2 NADH + H+
4 ATP

2 Pyruvic acid
• Products produced: 2 ATP, 2 NADH 2 NADH + H+

O2
O2 2 NAD+

2 Lactic acid
To citric
acid cycle
(aerobic
pathway)
 Glucose

Fate of Pyruvic acid

2 ATP

2 ADP

Fructose-1,6-
bisphosphate
• In presence of O2->acetyl-Coa
P P
• In absence of O2-> lactic acid
• Lactic acid returns to blood
• Reaches liver, comverted back to glucose
Dihydroxyacetone Glyceraldehyde
phosphate 3-phosphate
P P
2 Pi
2 NAD+

4 ADP

2 NADH + H+
4 ATP

2 Pyruvic acid
2 NADH + H+

O2
O2 2 NAD+

2 Lactic acid
To citric
acid cycle
(aerobic
pathway)
 Which type of situations would cause glucose to become lactic acid?
GLUCOSE
Situations where oxygen is lacking
O
When
• Intense exercise catabolized

• Umbilical cord compression LACTIC ACID 2 in in a less

than
optimum
O2 env’t
­ LACTIC ACID

Decreased pH

acidosis in foetus
https://www.berestonlaw.com/
11
2. Citric acid cycle :
In the presence of O2, pyruvic acid is converted to
acetyl-CoA, i a 2 carbon molecule.

It associates with oxaloacetic acid to produce citric

acid.

CAC produces
• ATP
• NADH and FADH2
• Carbon dioxide (CO2)

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FOCUS FIGURE 24.1 Oxidative Phosphorylation
Electron transport
Glycolysis Citric chain and oxidative
acid phosphorylation
cycle

ATP ATP ATP

Outer
mitochondrial Phase 1:
membrane Electron transport creates the proton gradient. Phase 2:
Chemiosmosis uses
Intermembrane H+
the proton gradient
to synthesize ATP.
space H+

H+
H+
Cyt c
Inner
mitochondrial e–
e–
membrane
(crista)
Q IV
III
I

e– II

e– 2 H+ + 1
O2 H2O
2 H+
ATP
NADH + H+ FAD V
synthase
NAD+
FADH2

ADP + P i ATP

1. Coenzymes 2. This creates an electrochemical 3. As H+ flows back across

(NADH + H+ and FADH2) gradient between the matrix and the membrane through ATP
help pump H+ out of the the intermembrane space. synthase, the synthase rotor
mitochondrial matrix spins, causing Pi to attach
Mitochondrial matrix to ADP, forming ATP.

§ C6H12O6 + 6O2 à 6H2O + 6CO2 + 36 ATP

 Glucose Anabolism
§ Anabolic reactions – synthesis of larger molecules from smaller ones

Glycogenesis – High ATP levels turn off glycolysis, glucose molecules are combined to form glycogen in liver and muscles

Glycogenolysis – when blood glucose levels drop, glycogen is broken down into glucose in the liver

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Gluconeogenesis

§ The process of forming glucose from noncarbohydrate molecules like proteins,

fats, glycerol, lactic acid when dietary sources of glucose are used up, and blood
glucose levels are dropping

§ Takes place mainly in the liver

§ Protects the body, especially the brain, from the damaging effects of
hypoglycemia by ensuring ATP synthesis can continue (Brain can only use
glucose not fatty acids, or aa or glycerol to make glucose)
§ happens in times of fasting and starving so very important for protecting the
brain

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 Quick Summary of Carbohydrate
Reactions

Glycolysis: Converts glucose to pyruvic acid

Glycogenesis: Polymerizes glucose to form glycogen
Glycogenolysis: Hydrolyzes glycogen to glucose monomers
Gluconeogenesis: Forms glucose from noncarbohydrate precursors

Figure 24.12 Quick summary of carbohydrate reactions

 17
Stage 1: GI Tract

Lipid/fat Metabolism
PROTEINS CARBOHYDRATES FATS

Amino acids Glucose and other sugars Glycerol Fatty acids

Stage 2: Tissue Cells

Glucose
Proteins Glycogen Triglycerides

Glycolysis
NH3 Pyruvic acid
CO2
Stage 3: Mitochondria
Acetyl CoA

Citric
acid
Infrequent cycle CO2

O2

H Oxidative phosphorylation
(in electron transport chain) H2 O

Catabolic reactions
ATP ATP ATP
Anabolic reactions
 1. Triglycerides:
§ Composed of three fatty acids bonded to a glycerol molecule
Glycerol
Glycerol

Triglyceride
Triglyceride

(c) Simplified drawing of the 18

same triglyceride.
 Fat globule
(in small
intestine)
Absorption of fats

Bile salts
1
Emulsification. Bile salts in the duodenum break large fat globules into smaller fat droplets, increasing
the surface area available to lipase enzymes.

2
Digestion. Pancreatic lipases hydrolyze triglycerides, yielding monoglycerides and free fatty acids.
Fat droplets
coated with
bile salts
3
Micelle formation. Micelles (consisting of fatty acids, monoglycerides, fat-soluble vitamins and
bile salts) ferry their contents to epithelial cells.

4
Diffusion. Fatty acids and monoglycerides diffuse from micelles into epithelial cells.

5
Chylomicron formation. Fatty acids and monoglycerides are recombined and packaged with
other fatty substances and proteins to form chylomicrons.

Enterocytes
of small
6
Chylomicron transport. Chylomicrons are extruded from the epithelial cells by exocytosis, enter
intestine
Lacteal lacteals, and are carried away from the intestine in lymph.
 A chylomicron is a lipoprotein
Cholesterol lipoproteins

Phospholipids

Triglycerides Phospholipids

20
A chylomicron travels to liver then blood and is processed into LDL and HDL

21
Difference btw LDL and HDL

• Both contain cholesterol

• LDL is 50% , can create deposits in vessles
• HDL has only 20% cholesterol and can bind LDL to take it out of the blood

• When taking blood levels, more important to measure form in which

cholesterol is transported in blood (and not total amount of cholesterol)
• Factors regulating blood cholesterol levels
• Liver produces cholesterol at a basal level regardless of dietary cholesterol intake
• Restricting dietary cholesterol does not markedly reduce blood cholesterol levels

• More important effect is relative amounts of saturated and unsaturated fatty acids
• Saturated fatty acids stimulate liver synthesis of cholesterol and inhibit cholesterol excretion from
body
• Unsaturated fatty acids enhance excretion of cholesterol into bile salts
Lipid Catabolism
1. Lipolysis
Degradation of triglycerides in CM produces glycerol and fatty
acids

1. Glycerol
• glycerol – pyruvic acid , eventually to acetyl-CoA, enters CAC à
ATP
• absolutely need oxaloacetic acid to make this happen

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Lipid Catabolism
1. Lipolysis

2.Fatty acids:
•fatty acids broken down 2C at a time and form acetyl CoA. Beta-oxidations
•so one fatty acid can produce A LOT of acetyl-CoA
•acetylCoA enters CAC à produces ATP
•lots of ATP produced from lipids compared to carbs

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Lipid Catabolism
1. Lipolysis

BUT
• if oxaloacetic acid [ ] is low, acetyl CoA is converted to ketones bodies by liver.

• Ketone bodies can be used by muscle and brain to make ATP

• But any extra ketone bodies then break down into acetone

26
 Lipid Anabolism: Lipogenesis
• Excess dietary glycerol and fatty acids are recombined to form triglycerides
• liver cells can synthesize lipids from glucose or aa (stimulated by insulin)
• Glucose is easily converted into fat since
– glucose can be converted to glycerol
– glucose can be converted to acetylCoA which is the starting molecule for the synthesis of
fatty acids
Glycolysis

Glucose

s is Glycerol
Stored fats in oly
adipose tissue Lip Lipogenesis
Triglycerides Glyceraldehyde 3-phosphate
Lip
Dietary fats oly
s is Fatty acids
Pyruvic acid Certain
bO
xid amino
atio
n acids

Ketone Ketogenesis (in liver) Acetyl CoA

bodies

Steroids Electron ATP

Cholesterol Citric transport
Bile salts chain
acid +
Catabolic reactions cycle CO2 + H2O
Anabolic reactions 27
 3. Protein metabolism

Catabolism:
• broken down into aa and form pyruvic acid or acetylCoA to enter Kreb’s
cycle (see pic at right)
• aa can also be changed and become intermediates of the Kreb’s cycle (ex:
oxaloacetic acid)

• can also be transformed into glucose (gluconeogenesis)

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 3. Protein metabolism
Anabolism
• protein synthesis occurs on ribosomes
•In liver, body forms proteins from non-essential aa by using intermediates in glycolysis, CAC; Diet must provide all essential
aa.
• peptide bonds created to make proteins

29
Absorptive vs PostAbsorptive State
Major metabolic thrust: Major energy fuel: Liver metabolism:
anabolism and energy storage glucose (dietary) amino acids deaminated and
used for energy or stored as fat
Glycerol and Glucose
Amino acids Glucose Amino acids
fatty acids

Keto acids
CO2 + H2O

+ ATP
Proteins Glycogen Triglycerides Triglycerides CO2 + H2O + ATP

(a) Major events of the absorptive state

Major metabolic thrust: Major energy fuels: Liver metabolism:

catabolism and replacement of fuels in blood glucose provided by glycogenolysis and amino acids converted to
gluconeogenesis; fatty acids, and ketones glucose (gluconeogenesis)

Proteins Glycogen Triglycerides Glucose Fatty acids Amino acids

and ketones

Keto acids
CO2 + H2O

+ ATP
Amino Glycerol and
Glucose Glucose
acids fatty acids

(a) Major events of the postabsorptive state

 Major Events and Principal Metabolic Pathways of the Absorptive State (2 of 2)

In all tissues:

CO2 + H2O
In muscle: Glycogen Glucose Gastrointestinal Glucose
tract + ATP

Protein

Amino acids Glucose Triglycerides

In adipose
tissue:

In liver: Glycogen Glucose

Keto acids
Fatty Glyceraldehyde
acids 3-phosphate Fatty Fatty
Glycerol
acids acids
Protein Glycerol

Triglycerides Triglycerides
CO2 + H2O

+ ATP

Figure 24.20b Major events and principal metabolic pathways of the absorptive
(b) Principal pathways of the absorptive state state
 Major Events and Principal Metabolic Pathways of the Postabsorptive State (2 of 2)

CO2 + H2O In adipose

Glycogen tissue:
+ ATP
2
Triglycerides
In muscle: Pyruvic and
Protein
lactic acids 3
4

Amino acids

In most tissues:
2
4 Triglycerides 3 Fatty
acids +
In liver: glycerol CO2 + H2O
Fatty acids
Pyruvic and Glycerol
Amino + ATP
lactic acids CO2 + H2O
acids Ketone
Ketone
+ ATP bodies bodies
4 2 3

Keto acids Glucose Blood glucose

1
Stored CO2 + H2O
glycogen In nervous
tissue: + ATP

(b) Principal pathways of the postabsorptive state

Figure 24.22b Major events and principal metabolic pathways of the postabsorptive state