Transcript Metabolism

Metabolism
Chapter 25
An Introduction to Cellular Metabolism
Figure 25–1
Essential Nutrients
45 – 50 molecules must be ingested.
This includes representatives from the 4 major
organic molecule groups, plus a number of
inorganic substances such as including water,
vitamins and minerals (Na, Fe, etc.)
The USDA has made major revision in its nutritional
recommendations.
http://www.health.gov/dietaryguidelines/dga2005/document/
It was never based on solid science
Nutrient –
A substance in food used by the body for growth,
maintenance, energy and repair.
USDA
• Carbohydrates: 271g (55%)
• Lipid:
total 65g (17%)
saturated 17g (7.8%)
• Protein:
91g (18%)
IOM for young adult female
130g (45 - 65%)
20 – 25%
56g (10 – 35%)
• Water: 1500 ml (average) per day.
Uses of nutrients
• Carbohydrate: Primary energy molecule. Also found on
cell membranes and as part of structure of connective
tissue matrix molecules
• Lipid: Energy storage, plasma membrane structure,
cushioning, steroid hormones.
• Proteins: Enzymes, receptors, hormones, structures of
all kinds. Must be “complete” or “complimentary” in order
to supply essential amino acids.
Nutrient Use in Cellular Metabolism
Essential amino acids
10 Essential Amino Acids
• 8 not synthesized:
– isoleucine, leucine, lysine, threonine,
tryptophan, phenylalanine, valine, and
methionine
• 2 insufficiently synthesized:
– arginine and histidine
4 Types of Nitrogen Compounds
1. Amino acids:
– framework of all proteins, glycoproteins, and
lipoproteins
2. Purines and pyrimidines:
– nitrogenous bases of RNA and DNA
4 Types of Nitrogen Compounds
3. Creatine:
– energy storage in muscle (creatine
phosphate)
4. Porphyrins:
– bind metal ions
– essential to hemoglobin, myoglobin, and
cytochromes
Energy Metabolism
• Metabolism = catabolism + anabolism
• Cellular respiration is a series of catabolic
reactions that provide energy for the
production of ATP
• This energy is used to generate ATP from
phosphorylation of ADP.
• It is a series of Redox reactions.
Energy Metabolism: Generation of ATP
Overview of aerobic respiration
Summary of
steps of
energy
metabolism
Generation of ATP by “substrate-level
phosphorylation”
Oxidative
phosphorylation
Overview of cellular respiration
Carbohydrate Metabolism
Oxidation of Glucose
C6H12O6 + 6 O2
6 CO2 + 6 H2O + 36 ATP + Heat
Glycolysis
It is the first
stage in
cellular
respiration
Steps
of
glycolysis
Aerobic vs
anaerobic
pathways
Overview of TCA (Krebs cycle)
TCA
(Krebs)
Cycle
Summary: The TCA Cycle
CH3CO — CoA + 3NAD + FAD + GDP
+ Pi + 2 H2O  CoA + 2 CO2
+ 3NADH + FADH2 + 2 H+ + GTP
The ETS creates
an chemiosmotic
gradient
The Electron Transport System
The ETS
Summary of ATP synthesis Gains & losses
Visual
summary of
cellular
respiration
Carbohydrate
Breakdown
and Synthesis
Figure 25–7
Glycogenesis/
Glycogenolysis
Gluconeogenesis
• Is the synthesis of glucose from
noncarbohydrate precursors:
– lactic acid
– glycerol
– amino acids
• Stores glucose as glycogen in liver and
skeletal muscle
Summary of metabolic pathways
Lipid metabolism: oxidation
3 Energy Benefits of Beta-Oxidation
1. For each 2-carbon fragment removed from
fatty acid, cell gains:
– 12 ATP from acetyl-CoA in TCA cycle
– 5 ATP from NADH
2. Cell can gain 144 ATP molecules from
breakdown of one 18-carbon fatty acid
molecule
3. Fatty acid breakdown yields about 1.5 times
the energy of glucose breakdown
Lipid
Transport
and
Utilization
Figure 25–9
5 Classes of Lipoproteins
•
•
•
•
•
Chylomicrons
Very low-density lipoproteins (VLDLs)
Intermediate-density lipoproteins (IDLs)
Low-density lipoproteins (LDLs)
High-density lipoproteins (HDLs)
Chylomicrons
• Are produced in intestinal tract
• Are too large to diffuse across capillary
wall
• Enter lymphatic capillaries
• Travel through thoracic duct:
– to venous circulation and systemic arteries
Distribution of
Other Lipoproteins: Step 1
• Liver cells synthesize VLDLs:
– for discharge into bloodstream
Distribution of
Other Lipoproteins: Step 2
• Lipoprotein lipase removes many
triglycerides from VLDLs:
– leaving IDLs
• Triglycerides are broken down:
– into fatty acids and monoglycerides
Distribution of
Other Lipoproteins: Step 3
• When IDLs reach liver:
– additional triglycerides are removed
– protein content of lipoprotein is altered
– LDLs are created
• LDLs are transported to peripheral tissues
to deliver cholesterol
Distribution of
Other Lipoproteins: Step 4
• LDLs leave bloodstream through capillary
pores:
– or cross endothelium by vesicular transport
Distribution of
Other Lipoproteins: Step 5
• In peripheral tissues:
– LDLs are absorbed through receptormediated endocytosis
• Amino acids and cholesterol enter the
cytoplasm
Distribution of
Other Lipoproteins: Step 6 & 7
• Cholesterol not used by the cell:
– diffuses out of cell
• Cholesterol reenters bloodstream:
– is absorbed by HDLs and returned to liver
Distribution of
Other Lipoproteins: Step 8
• In the liver:
– HDLs are absorbed
– cholesterol is extracted
• Recovered cholesterol is used:
– in synthesis of LDLs
– in excreted in bile salts
Distribution of
Other Lipoproteins: Step 9
• Free HDLs are released into bloodstream:
– travel into peripheral tissues
– absorb additional cholesterol
Composition
of
Lipoproteins
Proteins
• The body synthesizes 100,000 to 140,000
proteins:
– each with different form, function, and
structure
• All proteins are built from the 20 amino
acids
Amino Acid Catabolism
Figure 25–10 (Navigator)
Amination
Figure 25–11
Amino acid
use in TCA
cycle
Protein
metabolism
in the Liver
Summary: Pathways of Catabolism and
Anabolism
Figure 25–12
5 Metabolic Tissues
Each tissue has its own requirements
1.
2.
3.
4.
5.
Liver
Adipose tissue
Skeletal muscle
Neural tissue
Other peripheral tissues
Other Peripheral Tissues
• Do not maintain large metabolic reserves
• Can metabolize glucose, fatty acids, and
other substrates
• Preferred energy source varies:
– according to instructions from endocrine
system
Metabolic Interactions
•
•
Relationships among 5 components
change over 24-hour period
Body has 2 patterns of daily metabolic
activity:
1. absorptive state
2. postabsorptive state
Regulatory Hormones: Effects
on Peripheral Metabolism
Table 25–1
Pathways
of the
Absorptive
state
The effects of
insulin on
metabolism
The Postabsorptive state
Influences
of
Glucagon
on blood
glucose
levels
Lipid and Amino Acid
Catabolism
• Generates acetyl-CoA
• Increased concentration of acetyl-CoA:
– causes ketone bodies to form
Ketone Bodies
• Acetoacetate
• Acetone
• Betahydroxybutyrate
Ketone Bodies
• Liver cells do not catabolize ketone
bodies:
– compounds diffuse into general circulation
– peripheral cells absorb ketone bodies
• Cells reconvert ketone bodies to acetylCoA for TCA cycle
Ketone Bodies
• Are acids that dissociate in solution
• Fasting produces ketosis:
– a high concentration of ketone bodies in body
fluids
Ketonemia
• Is the appearance of ketone bodies in
bloodstream
• Lowers plasma pH, which must be
controlled by buffers
Ketoacidosis
• Is a dangerous drop in blood pH:
– caused by high ketone levels
– exceeding buffering capacities
Severe Ketoacidosis
• Circulating concentration of ketone bodies
can reach 200 mg dl:
– pH may fall below 7.05
– may cause coma, cardiac arrhythmias, death
Minerals and Vitamins
• Are essential components of the diet
• The body does not synthesize minerals
• Cells synthesize only small quantities of
few vitamins
Minerals and Mineral Reserves
Table 25–3
Minerals
• Are inorganic ions released through
dissociation of electrolytes
Importance of Minerals
• Ions such as sodium, chloride and
potassium determine osmotic
concentrations of body fluids
• Ions are essential:
– cofactors in many enzymatic reactions
– in many important physiological processes
Metals
• Each component of ETS requires an iron
atom
• Final cytochrome of ETS requires a
copper ion
Mineral Reserves
• The body contains significant mineral
reserves:
– that help reduce effects of variations in diet
The Fat-Soluble Vitamins
Table 25–4
Fat-Soluble Vitamins
• Vitamins A, D, E, and K:
– are absorbed primarily from the digestive tract
along with lipids of micelles
– normally diffuse into cell membranes and
lipids in liver and adipose tissue
Vitamin A
• A structural component of visual pigment
retinal
Vitamin D
• Is converted to calcitriol:
– which increases rate of intestinal calcium and
phosphorus absorption
Vitamin E
• Stabilizes intracellular membranes
Vitamin K
• Helps synthesize several proteins:
– including 3 clotting factors
Vitamin Reserves
• The body contains significant reserves of
fat-soluble vitamins
• Normal metabolism can continue several
months without dietary sources
The Water-Soluble Vitamins
Table 25–5
Metabolic Rate
• If daily energy intake exceeds energy
demands:
– body stores excess energy as triglycerides in
adipose tissue
• If daily caloric expenditures exceeds
dietary supply:
– body uses energy reserves, loses weight
Hormonal Effects
• Thyroxine:
– controls overall metabolism
– T4 assay measures thyroxine in blood
• Cholecystokinin (CCK):
– suppresses appetite
• Adrenocorticotropic hormone (ACTH):
– suppresses appetite
• Leptin:
– released by adipose tissues during absorptive
state
– binds to CNS neurons that suppress appetite
Heat Balance
Regulatory
pathways for
homeostatic
control of
body
temperature
Temperature regulation mechanisms
Maynard or Hans?