Integrated Metabolism

metabolism

all chemical reactions and pathways that occur to maintain life

anabolic reactions

synthesize complex molecules from simple precursors by utilizing the energy from ATP

catabolic reactions

break down macronutrients, releasing energy that can be transformed into ATP

Major fuel sources for muscle

fatty acids and glucose, but can also use ketone bodies if necessary

Major energy sources for the brain

primary fuel source is glucose, but can adapt to using ketone bodies

Major energy sources of red blood cells

glucose is the exclusive energy source because they don’t have mitochondria and can only perform anaerobic fermentation

Major energy source in the kidneys

Medulla: uses glucose and produces lactate

renal cortex: synthesizes and secretes glucose; can use lactate produced in the renal medulla; primary fuel source: fatty acids

Fed-Fast Cycle Stages

fed state: lasts 3 hours after meal

post-absorptive state: lasts 3-18 hours after a meal

fasting state: 18 hours to 2 days without additional food intake

starvation state (long-term fast): longer than 2 days without food

Describe glucose absorption during the fed state

the liver uses some of the glucose first. Around 2/3 pass into systemic circulation and are delivered to the body tissues. The glucose retained in the liver may enter glycolysis or be converted into glycogen. Excess glucose exceeding the liver’s glycogen storage capacity will be converted into fatty acids and triglycerides and delivered to adipocytes by VLDL

Describe the role of insulin during the fed state

Insulin is the dominant hormone of the fed state. It stimulates the cellular uptake of glucose, amino acids, and lipids, leading to their storage in tissues. This is critical during the fed state when large amounts of blood glucose must be removed to prevent hyperglycemia. Insulin also increases glycogen synthesis and FA synthesis

Where does most dietary glucose go during the fed state?

RBCs, brain, muscle, adipose tissue, and nervous tissue

What is the end product of glycolysis?

2 pyruvate

2 net ATP

2 NADH

2 H2O

What are the regulatory enzymes of glycolysis and which one is irreversible?

hexokinase (glucokinase)

phosphofructokinase-irreversible

pyruvate kinase

How much ATP does aerobic glycolysis produce?

30-32 ATP

What enzyme converts pyruvate to acetyl CoA and is it reversible?

pyruvate dehydrogenase and it is irreversible

End products of the TCA cycle for 1 glucose molecule

2 ATP, 8 NADH, 2 FADH, 6CO2

What does the TCA cycle do?

It oxidizes CHO, amino acids, and fatty acids, but can also use them as precursors for biosynthetic pathways like gluconeogenesis

glycogenesis

converts glucose to glycogen for storage

How many grams of glycogen can the liver and skeletal muscle store?

liver: 100g

skeletal muscle: 500g

lipogenesis

converts CHO and amino acids to free fatty acids, which are then incorporated as triglycerides in VLDL

How can acetyl-CoA leave the mitochondria?

it must be converted into citrate

How much cholesterol synthesis occurs in the liver?

20%

lipoprotein lipase

bound to capillary endothelium of adipose tissue and muscle; breaks down TAGG to FFA, which can then be used by the tissues

Describe characteristics of the post-absorptive state

glucagon levels start to rise

Hepatic glycogenolysis becomes the major provider of glucose to the blood; also occurs in the skeletal muscle

Hormonal regulation in the post-absorptive state

glucagon, epinephrine, cortisol, growth hormone

Glucagon

dominant hormone in the non-fed states

stimulates gluconeogenesis, glyconeogenolysis, FA oxidation, ketogenesis, and lipolysis

opposite of insulin

epinephrine

inhibits insulin release and stimulates glucagon release

stimulates glycogen breakdown, glycolysis, lipolysis, and increases FA uptake in the skeletal muscle

cortisol

released in response to low blood glucose levels; travels in circulation bound to albumin

stimulates lipolysis, gluconeogenesis, and glyconeogenesis

high levels often seen in starvation cause protein breakdown in the skeletal muscle

growth hormone

released during fasting and strenuous exercise

stimulates lipolysis and the release of FA from visceral and subcutaneous adipose tissue

Increases TAG uptake in the liver and stimulates lipoprotein lipase

inhibits protein breakdown and stimulates protein synthesis

glycogenolysis

breaks glycogen down into glucose, occurs in liver and skeletal muscle

gluconeogenesis

opposite of glycolysis, creates new glucose from a non-CHO substrate to help maintain blood glucose levels

occurs primarily in the liver and kidneys

Regulatory enzymes of gluconeogenesis

pyruvate carboxylase

fructose 1,6 biphosphate

glucose-6-phosphatase

beta oxidation (FA oxidation)

2 carbon acetyl-CoA unit removed from a fatty acid; produces a LOT of ATP

occurs within the mitochondria of the cell

ketogenesis

creation of ketone bodies from acetyl-CoA to use as fuel for the brain

occurs in the liver

What conditions can cause ketoacidosis?

starvation and diabetes

Processes during the post-absorptive state

gluconeogenesis, glyconeogenesis, ketogenesis, beta oxidation

Describe characteristics of the fasting state

hepatic glycogen is depleted

increases in glucagon and cortisol stimulate protein breakdown

lipolysis in adipose tissue progresses

ketone formation starts to rise

Describe the alanine-glucose cycle

as muscle breaks down during fasting, the N2 is transanimated to alpha ketoglutarate to make glutamate. The glutamate can be converted to alanine to pyruvate to glucose via gluconeogenesis

How does the body try to spare proteins during the starvation state?

accelerated lipolysis

increased use of FFAs as fuel in the kidneys, liver, heart, and skeletal muscle

increased use of glycerol for gluconeogenesis

ketogenesis after oxaloacetate depletion