Transcript ANPS 020 Cornbrooks 02-28

Metabolism
Chapter 25
Metabolism and Energetics
Do not focus on the specific aspects
like enzymes and organic structures
1
Context
2
Source: USDA
Obesity Trends Among U.S. Adults
1998
1990
2006
No Data
<10%
10%–14%
15%–19%
20%–24%
25%–29%
≥30%
Global Projections for Diabetes
2003-2025 (millions)
48.4
58.6
21%
23.0
36.2
57%
14.2
26.2
85%
World Projections
2003 = 194 million
2025 = 333 million
Increase : 71%
Source: Diabetes Atlas 2003
7.1
15.0
111%
39.3
81.6
108%
19.2
39.4
105%
43.0
75.8
76%
4
Diseases correlated with to obesity
Complications of Obesity Affect Doctors!
Pulmonologist:
obstructive sleep apnea
hypoventilation syndrome
Idiopathic intracranial
hypertension
Stroke
Cataracts
Gastroenterologist:
Nonalcoholic fatty liver
disease
Coronary heart disease
Diabetes
Dyslipidemia
Hypertension
Gall bladder disease
Severe pancreatitis
Gynecologist
Cancer
abnormal menses
infertility
polycystic ovarian syndrome
breast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate
Osteoarthritis
Skin
Gout
Phlebitis
venous stasis
5
A NEW LOOK
(Walter Willett)
6
7
Recommended Nutrient Content of a
Weight-Reducing Diet
Protein
15%
8%–10% Saturated
fatty acids
Fat
30%
Carbohydrate
55%
10%
Polyunsaturated
fatty acids
15%
Monounsaturated
fatty acids
Calories: 500–1000 kcal/d reduction
Cholesterol: <300 mg/d
Fiber: 20–30 g/d
Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults–
8
The Evidence Report. Obes Res 1998;6 (suppl 2).
How well do they work ? (12 month study)
Average weight
loss of 2.1-3.3 kg
over 12 months
No one diet worked
better than any other
9
Diet and Behavioral Intervention:
Long-Term Effect on Weight Loss
5
Weight
change
(kg)
0
–5
–10
Very low calorie diet (VLCD)
Modified diet + behaviour therapy
–15
VLCD + behaviour therapy
–20
1
Intervention
2
3
4
Years after intervention
5
10
Adapted from Wadden TA. Ann Intern Med 1993; 119: 688–93 with permission
One
Solution
Eat Food
Not too much
Mostly Plants
11
A Second Solution
How far is two pounds from here?
12
The Third, Last and BEST Solution
Diet
With
Exercise
+
Consider genetics
and age at a
minimum
Ready to head back?
14
What Needs to be Explained
15
FOODSTUFF METABOLISM
QUESTIONS YOU SHOULD BE ABLE TO ANSWER
What are the major foodstuffs you eat?
Where do they come from?
Digestive Sys.
How are they broken into the building blocks
How do they get into the body?
How / Where are they stored?
How are they recovered from storage?
What can they be used for and how?
Metabolism
What about the waste products?
How is all this regulated?
16
Gut Absorption: Carbohydrate and Protein
17
Absorption: Fat
GI system
18
cytoplasm
19
OVERALL METABOLISM: THE BIG PICTURE
(hydrolysis)
Simple molecules and
monomers such as glucose,
amino acids, glycerol, and
fatty acids
Complex molecules and
polymers such as glycogen,
proteins, and triglycerides
(dehydration)
20
DEFINITIONS
Metabolism:
Sum total of all bodily chemical processes
Related to foodstuff storage, mobilization,
energy recovery and use
Metabolic Pathways:
Sequences of many chemical reactions that allow
the body to synthesize or break down molecules
Anabolism:
Building molecules
Catabolism:
Breaking down molecules
Energy:
Ability to do work
21
22
23
DESIGN PRINCIPLES
ECONOMY / EFFICIENCY
FLEXIBILITY
COMMON CURRENCY
FRAMEWORK AND ENVIRONMENT
24
Glucose, 6 carbons
Glycolysis
FATS
Proteins
Amino
acids
O2
Pyruvate, 3 carbons (2X)
Acetyl CoA
Kreb’s (TCA)
cycle
Oxidative phosphorylation
Electron Transport System
ATP
25
+ CO2, H2O, heat
ECONOMY / EFFICIENCY
MANY SMALL
STEPS
Efficiency
CARS: ABOUT 15%
US: ABOUT 40%
26
FLEXIBILITY: WHAT WE USE ENERGY TO DO
27
A MOST IMPORTANT DEMAND
THE BRAIN ALWAYS MUST BE
SUPPLIED WITH GLUCOSE
Total glucose in the body is enough to supply the
Whole body energy needs for less than a day!
28
COMMON CURRENCY: ATP
Our “currency”
29
COMMON CURRENCY
Structure of ATP
- Formation of high
energy covalent bonds
- Separation of the
bonds yields energy
30
FRAMEWORK
KEY STRATEGIES
SOURCES (dietary - food)
CLEARING HOUSES (absorption – in GI)
STOREHOUSES (liver, muscle, adipose, etc)
INTERCONNECTED PATHWAYS
REGULATION
31
Glucose, 6 carbons
Glycolysis
ATP
Proteins
FATS
Amino
acids
Pyruvate, 3 carbons (2X)
Acetyl CoA
Kreb’s (TCA)
cycle
ATP
ATP
Oxidative phosphorylation
Electron Transport System
32
+ CO2, H2O, heat
Overview: building blocks to ATP
33
THE CENTRAL PATHWAY
Glucose Metabolism
BLOOD
34
High energy
intermediate
ATP
35
Glycolysis vs Gluconeogenesis
Glycogenesis:
- generation of glycogen
from glucose
Glycolysis =
metabolism
of glucose; it
is anaerobic
ie. without O2
Gluconeogenesis
- generation of glucose
from noncarbohydrate
carbon substrates
36
Entrance of
carbon
intermediates –
specifically
Acetyl-CoA into
mitochondria
37
Glycolysis ends with Pyruvate Acetyl CoA enters into the Mitochondrion:
The Krebs
(TCA) cycle
Enters into
mitochondria
High energy intermediates =
FADH2 and NADH
Krebs or
TCA cycle
38
CENTRAL PATHWAY
Make High Energy “Intermediates” (NADH & FADH)
39
High energy intermediates carry protons (H+) to the electron
transport system
40
CENTRAL PATHWAY
Oxidative Phosphorylation /
Electron Transport
Generation of ATP or high energy intermediates
41
Output: ATP, CO2, Heat, Water
Electron Transport System –
requires O2 = aerobic
42
The electron transport system
is where oxidative
phosphorylation occurs
43
Oxidative phosphorylation occurs in the
Electron Transport System
H+ come from high energy intermediates
hydrogen ions pumped into the intermembrane space provides
concentration gradient to generate ATP
44
ATP: Talley Sheet
32 of 38
ATPs
With O2= 38 ATP
Without O2 = 2 ATP
45
46
GLUCOSE STORAGE: GLYCOGEN
Glycogen
(ANPS-19)
47
CONNECTING FAT - storage
FATS
Glycerol
Fatty acids
How does a high
carbohydrate diet
lead to obesity?
NOTE ONE-WAY vs
TWO-WAY ARROWS
(ANPS-19)
48
CONNECTING PROTEIN - storage
Proteins
(ANPS-19)
49
FOOD FOR THOUGHT
Brain Must Always have glucose
There is not enough glucose in our bodies
to cover calories needed in a single day
Yet we can fast for weeks!
50