Lecture 20: Basic Concepts in Metabolism Flashcards
Two opposing streams of chemical reactions
catabolism vs. anabolism
Catabolic Pathways
break down macromolecules into smaller molecules, thereby generating both a useful form of energy (energy carriers) for the cell and some of the small molecules that the cell needs as building blocks
Anabolic Pathways
Biosynthetic. Pathways use the energy harnessed by catabolism to drive the synthesis of many endogenous macromolecules that form the cell.
Amphibolic
both anabolic and catabolic
Fed state and Fast State
We are activating BOTH pathways (anabolic and catabolic pathways)
Energy carriers as….
energy currency
Macromolecules
Rich sources of energy since much of the energy used to form them is stored within chemical bonds that hold them together
The energy released by the oxidation of macromolecules must be?
stored temporarily before it can be channeled into the synthesis of other molecules needed by cells
There are two major categories of energy carriers
- Chemical bond energy
- Reducing equivalents
The energy is stored as high-energy chemical (phosphate) bond
Nucleotides/nucleoside tri-phosphates (NTPs) such as ATP, GTP, CTP, UTP, and dTTP all carry chemical bond energy in the form of high-energy phosphoanhydride bonds
ATP is the most _________ energy carrier in the cell, but it cannot be?
Abundant, but it cannot be stored (too unstable). It is produced/used as needed in the cell that produces it.
AMP is a signal of?
Low energy in the cell
These molecules diffuse within?
Diffuse within the cell and thereby carry their bond energy form sites of energy generation to sites where energy is. Used for cellular activities.
The energy is stored in electrons as reducing equivalence
Specialized energy carriers (nucleotide derivatives) accept (oxidized form) and donate (reduced form) electrons. Produced ATP as needed.
Water-soluble electron carriers
NAD+ (oxidized, energy poor)
NADH (reduced, energy rich)
NADP+ (oxidized, energy poor)
NADPH (reduced, energy rich)
Membrane associated electron carriers
FAD (ETC Complex II)
FADH2 (ETC Complex II)
FMN (ETC Complex I)
FMNH2 (ETC Complex I)
Water soluble precursor
Niacin (Vit B3)
Membrane associated precursor
Riboflavin (Vit B2)
Adding an electron produces an
reduced form of the molecule
Why are there two pools of carriers? NAD+ and NADP+
Depending on where you are moving to, you need different means of transportation. Environment dependent.
NAD+/NADH signifiance
Catabolic. To accept energy in catabolic reactions. Oxidized form (NAD+) is preferred. (A lot of taxis available to accept passengers once they are ready to go)
NADP+/NADPH significance
Anabolic. To donate energy in anabolic reactions. Reduced form (NADPH) is preferred. (We don’t want the body to be waiting to make cells, it needs to be ready right away).
Which are preferred?
In Catabolic reactions, Oxidized form (NAD+) is preferred. Anabolic reactions - reduced form (NADPH) is preferred. Water
Oxidized to Cystolic ratio & rationale (NAD+)
NAD+: NADH
700: 1
Need NAD+ ready to accept energy from catabolic reactions.
Energy is extracted from macromolecules (carbohydrate, protein, or fat) via?
Oxidation of metabolic fuels, resulting in end waste products: CO2 and H2O
Oxidized to cystolic ratio & rationale NADP+/NADPH
NADP+/NADPH
1:10
Need NADPH ready to donate energy for anabolic reactions.
Proteins in Fed/Absorptive State
from a dietary source
dietary proteins of various forms
Proteins in Fast/Post absorptive state
from endogenous body reserves
endogenous muscle proteins and cellular proteins
Carbs fed/absorptive
from dietary source
dietary carbohydrates of various forms: mono, di, oligo, polysaccharides
Lipids fed/absorptive
Carbs fast/post-absorptive
from endogenous body reserves
Lipids fast/post-absorptive
Proteins are broken into
Carbohydrates are broken into
Lipids are broken into
II: Building blocks (via various pathways) to….
a common intermediate, acetyl CoA
There is no dedicated storage for?
III. TCA cycle oxidizes what to what? Energy released is what?
NADH, FADH2, and GTP
Energy of NADH and FADH2 is released via? Used by? Requires?
Via ETC, and used by ATP synthase to produce ATP. This process requires ATP
Insulin/Glucagon goal
to maintain normoglycemia (glucose homeostasis) and to regulate energy metabolism
Fed
-0-4 hours after a carbs containing meal
-Insulin will be at high levels and glucagon will be at low levels
-High insulin/glucagon ratio: helps to lower blood glucose levels
Lack of insulin or its “ineffectiveness”
Results in diabetes
Short-term fasting
5-24 hours after a meal with carbs
Insulin is low
Glucagon levels are high
Low insulin/glucagon ratio: to maintain a minimal blood glucose levels
Long-Term fasting
Insulin signaling receptor and effects?
Receptor Tyrosine Kinase (RTK)
-Liver, adipose tissue, muscle
RTK phosphorylation –> signaling cascade –> increased general phosphatase activities
- De-phosphorylated state for the selected metabolism-specific enzymes (altered enzyme activity)
- Gene expression (altered enzyme quantity)
Glucagon signaling receptor and effects?
Gs coupled receptor (Ga-s)
(Liver, kidney)
Epinephrine signaling receptor and effects?
cAMP –> increased PKA activity
Liver self-sustaining
Cortisol signaling receptor and effects?
Fed/Absorptive State Liver (Self Sustaining)
-0-4 hours after a meal
-High I/G ratio
-Energy generation
- Liver glycolysis
Short Term Fasting: Liver Service to Others
- Service 1 - Liver glycogenolysis: glycogen to glucose for export
- Service 2 - Liver gluconeogenesis (slow): non-carb precursors –> glucose for export
- Service 3 - Ketogenesis (slow): acetyl-CoA (mito) –> ketones for export
Long-term liver fast (Self-sustaining)
More than 24 hours post mixed meal.
LOWER I/G ratio.
- Adipose tissue lipolysis: TAG –> FA + glycerol.
- B-oxidation (FA oxidation): Fatty acids –> acetyl-CoA (mito)
3.
Long-Term fasting Liver Service to others
Service 1: NOT glycogenolysis
Service 2: MORE/HIGH gluconeogenesis: Non carb precursors –> glucose for export
Service 3: Ketogenesis (high): acetyl-coA (mito) –> ketones for export
Service Liver Fed/Absorptive state
- Liver glycogenesis: Glucose-6-P –> glycogen
- LIpogenesis: TAG synthesis “from scratch” (de novo) in two steps
- De novo fatty acid synthesis: Acetyl-CoA (cyto) –> fatty acyl-CoA
-TAG synthesis: Fatty acyl-CoA + glycerol-3-P –> TAG
Service Liver Short-Term fast/post-absorptive state
-5-24 hours after a mixed meal
-Low I/G ratio
Adipose tissue lipolysis: TAGs –> fatty acids + glycerol
Service Liver long-term fast/post absorptive state
Lysis vs. Genesis Table
